Volume 26 Issue 1

SPRING/SUMMER 2020

262 th newsletter of the myelodysplastic syndromes foundation Anniversary MDS NEWS HIGHLIGHTS

FROM THE GUEST EDITOR’S DESK I EVALUATION OF ADULTS FOR FAMILIAL MYELOID MALIGNANCY PREDISPOSITION: EYES ON THE PRIZE OF PREVENTION Presented by: Jane Churpek, MD, MS UW Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin

PLAN TO ATTEND

16TH INTERNATIONAL CONGRESS ON MYELODYSPLASTIC ASH 2020: MDS FOUNDATION SYNDROMES BREAKFAST SYMPOSIUM May 5–8, 2021 Toronto, Canada December 4, 2020 San Diego, California

IN THIS ISSUE TABLE OF CONTENTS

FROM THE GUEST EDITOR’S DESK 2 MDS FOUNDATION MEMBERSHIP 25

MEETING HIGHLIGHTS & ANNOUNCEMENTS PATIENTS AND CAREGIVERS ASH 2020: MDS Breakfast Symposium 7 LIVING WITH MDS FORUMS 27 2nd Latin American MDSF Symposium 8 IN THE NEWS 28 RESEARCH TESTIMONIALS 31 International Working Group for 9 Prognosis in MDS OUR PATIENT STORIES 32 MDS/MPN International Working Group 11 OUR CAREGIVER STORIES 38

MDS FOUNDATION LEADERSHIP 13 AML CORNER 40

MDS AWARENESS WALKS 14 MPN CORNER 45

MDS LITERATURE HIGHLIGHTS 15 CONTRIBUTIONS TO THE FOUNDATION UPDATES IN MDS 18 Gifts 50 CORD BLOOD REGISTRY 19 Memorial Donations 55

MDS CENTERS OF EXCELLENCE 20 Living Endowments 56 www.mds-foundation.org FROM THE GUEST EDITOR’S DESK

GUESTXXXXX EDITORIAL

EVALUATION OF ADULTS FOR FAMILIAL MYELOID MALIGNANCY PREDISPOSITION: EYES ON THE PRIZE OF PREVENTION thrombocytopenia (90,000/microliter) dysplasia can be observed at baseline in found incidentally on laboratories done at a individuals with known familial myeloid preventative care visit. He feels in his usual malignancy syndromes due to germline state of health and denies recent infections, gene defect-related abnormalities in bleeding, or fatigue. A bone marrow biopsy hematopoiesis. This makes an MDS and aspirate reveal a hypocellular marrow diagnosis based on dysplasia alone with prominent erythroid dysplasia and 4% especially challenging and has created blasts. Karyotype is 46,XY[20]. calls for hereditary syndrome-specific criteria for MDS diagnosis.8,9 JANE E. CHURPEK, MD, MS PROGRESS IN THE PROCESS Patterns and Probability UW Carbone Cancer Center, At face value, this case is University of Wisconsin straightforward. He now has a new Studies of germline mutation prevalence School of Medicine and Public Health diagnosis of MDS with single lineage in unselected “sporadic” MDS/AML cases Madison, Wisconsin dysplasia and can be managed are beginning to define how common accordingly. However, if his hematologist hereditary myeloid malignancy pre- INTRODUCTION has incorporated universal family history disposition syndromes are in adults. For Advancements in the field of familial screening into his/her clinical practice as a example, a recent French series found myeloid malignancy predisposition in only growing number of hematologists are, 1 causative germline mutations in DDX41 in 10 a few years have been remarkable, taking out of every 7 to 9 similar adult myeloid 2.4% of 1385 adults with MDS/AML. us from rarely thinking about a hereditary malignancy patients will report at least one Early data from the BEAT AML Master trial, contribution to our adult patients’ histories close relative with a hematologic which is attempting to collect a skin biopsy to now a growing number of mainstream malignancy.(unpublished data,6,7) In this on all newly diagnosed AML patients, also clinical guidelines including and encour- particular patient’s case, he was especially found DDX41 mutations in 2.8% of 176 11 aging thought of these disorders in every worried about his blood count values patients age 60 or older. The National case.1-3 Each year, the list of genes and because he had two siblings who died of MDS Natural History Study (NCT disorders helping to explain the hereditary myeloid malignancies: one of MDS and the 02775383) is collecting germline samples contribution to another subset of patients other of AML (Figure 1A). on its planned 3500 newly diagnosed with myeloid malignancies grows,4,5 and Does this new information impact his patients, which will hopefully better define studies of the biological pathways diagnosis? YES. Based on the family prevalence estimates specifically in MDS disrupted are shedding light into early history alone, unless there is a major cases.12,13 Optimal germline samples, events in myelodysplastic syndromes known shared exposure risk factor, this comprehensive gene lists, expert rare (MDS) initiation. These are all FANTASTIC family warrants a clinical diagnosis of a variant interpretation, as well as follow-up developments. However, we are still a long familial MDS/AML syndrome. Communicating functional testing and family-based way off from maximizing the potential of this information to the pathologist who segregation studies of rare variants will be familial myeloid malignancy predisposition made the MDS diagnosis will change the critical to maximizing information gained assessment for MDS patients worldwide and bone marrow diagnosis line to add the from these large scale studies. using knowledge gained toward the following descriptor from Table 17 in the Case series of families with each ultimate goal of preventing MDS/acute World Health Organization myeloid myeloid malignancy predisposition myeloid leukemia (AML). Let us reflect on neoplasm classification guidelines: syndrome from different settings around the progress and critical needs for future progress myeloid neoplasm with germline ____ world are also helping to refine patterns by working through an illustrative case. mutation.1 The next challenge is to find the suggestive of one syndrome versus others. gene that fills in that blank. Cytopenias at initial MDS/AML diagnosis CASE EXAMPLE For low-grade MDS diagnoses, the with a bone marrow featuring hypo- A 63-year-old man presents for pathologist may also need to reevaluate cellularity, prominent erythroid dysplasia, hematology evaluation due to a three- the bone marrow with this new information and a normal karyotype are all classical month history of neutropenia (absolute to ask whether an overt MDS diagnosis is findings in familial MDS/AML due to neutrophil count 900,000/microliter) and warranted. Single or even multilineage DDX41 mutation.10,14,15 For DDX41,

2 series from the United States, Japan, Taiwan, and France have demonstrated different recurrent mutation sites within the DDX41 gene by country that could contribute to gene by ethnic background specific features.10,15-17 In contrast, de novo AML with M1 or M2 morphology and double CEBPA mutations without preceding blood count abnormalities would have suggested familial AML due to CEBPA mutation.18 MDS featuring dysplastic megakaryocytes, increased reticulin fibrosis, and often monosomy 7 is common in GATA2 deficiency syndrome.19,20 While initially intimidating, recognizing these patterns can be just like a good resident morning report. “Did Mr. X have a history of lymphedema? NO. How about pulmonary fibrosis? NO.…” In this Figure 1. Clinical presentation details that aid in familial myeloid malignancy syndrome process, yeses are more informative than diagnosis noes because all of these disorders are children are too young to know what may infectious disease history rounds out this incompletely penetrant for each feature. happen to them over time. Three affected evaluation.24 The clinical history often has This means that a patient can still have siblings could result from an autosomal clues that are easy to overlook if not familial platelet disorder with myeloid dominant pattern with incomplete intentionally seeking them. Our patient has malignancy predisposition (FPD) even if penetrance, meaning the parent who also no notable findings, a pattern also they do not have the characteristic carries the mutation did not develop a consistent with familial MDS/AML due to preceding history of thrombocytopenia or myeloid malignancy in their lifetime. This DDX41 mutation. bleeding tendency. Similarly, they can would be the most common pattern for Functional Testing and Genetics have GATA2 deficiency syndrome without adult-onset familial myeloid malignancy a clinical history of lymphedema or warts. syndromes, but autosomal recessive or For those lucky enough to have ready Arming oneself with tables from the other patterns are also possible. access to germline and acquired multi- literature,4 rote memorization, or one’s Next, note the median age at gene tests, one may consider just skipping own mnemonics (GATA2 deficiency MDS/AML presentation (Figure 1B). Our the memorizing and quizzing to wait for syndrome has CLAW: CMML/MDS, patient’s family’s median is 63 years, fitting the genetic tests to provide the answer. Lymphedema, Atypical infection, Warts) best with the median age of onset of 63 Well, unfortunately, it’s not so can aid in pattern recognition. years observed in familial MDS/AML due straightforward. Outside of a small number Recognizing syndrome-specific features to DDX41 mutation versus the 19, 25, and of recurrent mutations affecting multiple can even yield a legitimate clinical 33 years observed in GATA2 deficiency, families, the germline mutations identified diagnosis. In fact, expert clinicians are familial AML due to CEBPA mutation, and in the majority of families with most of right 91% of the time in clinically FPD, respectively.14,15,18,22,23 Presenting these syndromes will be unique or diagnosing a specific inherited bone and historical blood counts, bone marrow “private” to a single family. Thus, if clinical marrow failure syndrome later confirmed cellularity, lineage-specific dysplasia(s), laboratories have never seen this variant molecularly through genetic testing.21 With karyotype, and acquired gene mutations before, all of the work that was put in practice, you can do it too! can also be helpful as noted in the patterns characterizing the clinical phenotype Going through this process for the described above. In his case, the prominent above can really pay off—making a patient above (Figure 1A-D), first, consider erythroid dysplasia, hypocellular marrow variant that would otherwise end up in the possible inheritance patterns. Keep in mind with presenting cytopenias, and normal purgatory of genetics, a so-called variant the size of the family and age of both karyotype are all classical findings in of uncertain significance (“VUS”), instead affected and unaffected individuals, familial MDS/AML due to DDX41 be classified as a clinically useful likely paying attention to whether the unaffected mutation.14 A review of systems asking key pathogenic or pathogenic variant that can individuals have lived long enough to targeted questions such as the presence of be acted upon. Functional tests, where develop features. For our patient, his anomalies, pulmonary fibrosis, and an available, such as chromosome breakage

3 testing for Fanconi anemia, can also cinch a clinical diagnosis or aid in interpretation of genetic variants identified. Thus, the sum of careful clinical phenotyping, genetic testing, and functional tests is greater than any individual part in making a diagnosis (Figure 2). Ongoing efforts to improve rare variant classification in familial myeloid malignancy predisposition genes take advantage of this fact, incorporating syndrome-specific clinical features and functional tests to better differentiate the benign from clinically actionable variants and hopefully minimize VUSs.25 If an acquired mutation panel is Figure 2. Familial myeloid malignancy predisposition work-up elements: the sum is performed along with germline testing, the greater than its parts combined mutational pattern can further suggest a likely diagnosis. For example, if for the patient and identify those at risk in diagnosis can impact the interpretation of our patient had had a myeloid malignancy the family for counseling and risk blood and bone marrow findings, the focused panel that included DDX41, we management. official World Health Organization would have identified both his germline classification, and management of MDS DDX41 mutation (p.D140fs) as well as an CRITICAL NEEDS TO KEEP patients. Critical needs to keep the acquired DDX41 mutation (p.R525H), a MOMENTUM GOING momentum going and maximize potential recurrent mutation that is commonly Adult hematology is experiencing a benefit of familial myeloid malignancy acquired on the previously normal allele at major paradigm shift going from the predisposition assessment for clinical care the time of myeloid malignancy in this assumption that familial predisposition is and science are outlined below. syndrome.26 Because several of the exceedingly rare (Figure 3) to growing hereditary myeloid malignancy predis- recognition by both patients as well as Education position genes are frequently mutated clinicians at the time of diagnosis that the First and foremost, investment in somatically in MDS, such as RUNX1 and family history is important. A second hereditary hematology-focused educational TP53,27 these genes are already on most paradigm shift is also occurring. This one opportunities for diverse disciplines, such acquired mutation panels used for MDS involves recognition that paired germline as genetic counselors, medical geneticists, diagnostic and prognostic purposes. Some and acquired genetic assessment at benign and malignant hematologists, centers are further adapting acquired mutation panels to specifically include additional hereditary myeloid malignancy predisposition genes that are not yet prognostic or predictive for MDS therapeutic purposes but instead to screen for a hereditary etiology. Although most of the mutations found in an MDS sample will be acquired, DDX41 is different because the majority of the mutations found in this gene are germline.10,28 Thus, consenting patients to MDS “acquired” panels, especially if adapted for screening the germline, should acknowledge this intention. Overall, paired germline and acquired multi-gene testing along with clinical phenotyping and functional testing have the greatest chance of providing a molecular diagnosis to inform management Figure 3. Estimated proportion of MDS cases with an underlying inherited risk component

4 primary care providers, nurses, and Collaboration state, such as those in the Fanconi anemia advanced practitioners, is crucial to or telomere biology disorder pathways or Inherent in understanding the clinical helping more patients with MDS or who even SBDS are being found more and functional significance of each are at risk for MDS be recognized. With frequently than expected by chance in individual genetic variant is studying it in more practitioners comfortable with the patients with MDS/AML.30 Are these as many people in diverse ethnic spectrum of hematologic diagnoses and actually contributors to MDS/AML risk and backgrounds as possible. However, with vocabulary and aware that it is possible to if so, by how much do they increase risk? increasing regulation and restrictions being have hereditary forms of blood disorders placed on data and sample sharing across Biologically, why does a particular presenting across the lifespan, it is more international lines, our field will need to get germline mutation increase risk of likely that each patient bringing their own creative to maximize utility of data MDS/AML and by how much is the lifetime personal or family history of blood gathered from individual families across risk elevated? What is/are the triggering disorders to attention will be acknowledged the world. Formulating and adhering to event(s) that lead from the at-risk state to and given the opportunity to pursue the consensus clinical care guidelines that can overt MDS/AML? From what source(s) do etiology. A formal genetic hematology then be regularly reassessed with objective these triggers arise (e.g. are DNA fellowship for hematologists, geneticists, data would hasten evidence-based clinical damaging events due to endogenous cell and/or bioinformaticians in training is management progress. Clinical and metabolism-related exposures or are they possible and would foster talent development research teams agreeing on what key from external exposures like smoking)? for future discoveries and improvements in variables to collect over time and uniform How can we intervene on this process to clinical care and implementation. data formats would make analysis of data prevent MDS/AML or at least slow progression? Access across sites easier. Adopting methods used in other fields, like federated data networks A few recent studies have begun to Access to both germline and acquired that allow analysis of data across sites shed light on effects of the mutations genetic testing in MDS must be improved. without actually moving the data out of an themselves. For example, clonal Access in this context is multipronged from individual site, may be helpful. Seeking out hematopoiesis (CHIP) is a known marker of access to clinicians at the bedside who 31 and encouraging thought leaders in fields future MDS/AML risk. However, the recognize whom to test and either are like data science and engineering to get actual initiating events in this process have comfortable with informed consent and involved in hematology could further remained unclear. A recently described navigating the entire testing process or are inform new methods. autosomal recessive familial MDS/AML willing to make the connection to someone syndrome caused by biallelic or compound who is. Access also requires the ability to Research heterozygous mutations in MBD4 has collect appropriate samples, such as skin Many key questions still remain to be highlighted the role of DNA repair on fibroblasts or hair follicles for germline tests, answered. Clinically, despite a growing CHIP initiation and MDS/AML risk.32 as well as laboratories providing affordable gene list, only about 30% of familial Specifically, MBD4 is a DNA glycosylase assays with comprehensive and up to date MDS/AML cases like our case presented involved in repairing methylation damage gene lists, focused hereditary and acquired here will be explained by currently known through the base excision repair pathway. hematology genetics expertise to maximize syndromes.29 Thus, what other genes and Without this gene, there is a remarkable interpretation potential, and turnaround their variants contribute to MDS/AML risk accumulation of C>T transition mutations. times relevant for the care of patients with (Figure 3)? In familial MDS/AML as in Interestingly, DNMT3A appears particularly urgent diagnoses. Access also requires other hereditary cancer syndromes such as affected with multiple different DNMT3A financial investment from insurance hereditary breast cancer susceptibility, the clones found in the blood and a resulting companies, hospitals, and/or governmental genes with the largest effect on AML with myelodysplastic related changes agencies willing to provide coverage to susceptibility and those that account for the with a remarkably high mutational burden pay for testing to avoid financial toxicity to greatest proportion of cases will be the overall. This syndrome is unique in its more patients. Finally, access requires systems easiest to find. Figuring out the very rare or direct link to a specific DNA repair deficit change to allow all of this to happen the variants that only increase risk by a as a major contributor to the CHIP initiating seamlessly in the clinic so it can more easily small to moderate amount and are, event(s). Recent work in several other be incorporated into already complex care therefore, more common in the population inherited bone marrow failure syndromes needs and make it more likely that many will be much harder. For example, has also highlighted syndrome-specific practitioners can adopt genetic testing into heterozygous pathogenic or likely CHIP features that inform underlying their own practices. pathogenic variants in genes that usually pathogenesis. For example, a high cause MDS/AML predisposition in the proportion of individuals with Shwachman homozygous or compound heterozygous Diamond syndrome develop TP53-mutated

5 CHIP, often with multiple different TP53 single center analysis. PLoS One. 2019; prognosis of GATA2-related myelodysplastic mutated clones, by the age of 2033 14(4):e0215453. syndromes in children and adolescents. Blood. 2016;127(11):1387-1397;quiz 1518. whereas individuals with FPD who carry a 7. Wartiovaara-Kautto U, Hirvonen EAM, Pitkanen E, et al. Germline alterations in a 21. Ghemlas I, Li H, Zlateska B, et al. Improving germline RUNX1 mutation also develop consecutive series of acute myeloid leukemia. diagnostic precision, care and syndrome early-onset CHIP, but involving many Leukemia. 2018;32(10):2282–2285. definitions using comprehensive next- different genes.29 Further study into the 8. Hasle H, Niemeyer CM, Chessells JM, et al. generation sequencing for the inherited bone exact inciting events in CHIP initiation A pediatric approach to the WHO marrow failure syndromes. J Med Genet. 2015;52(9):575–584. whether stochastic or exacerbated by classification of myelodysplastic and myelo- specific endogenous or exogenous proliferative diseases. Leukemia. 2003; 22. Liew E, Owen C. Familial myelodysplastic 17(2):277–282. syndromes: a review of the literature. exposures will undoubtedly advance our 9. Kanagal-Shamanna R, Loghavi S, DiNardo Haematologica. 2011;96(10):1536–1542. understanding of pathogenesis and get us CD, et al. Bone marrow pathologic 23. Wlodarski MW, Collin M, Horwitz MS. closer to the goal of prevention. abnormalities in familial platelet disorder GATA2 deficiency and related myeloid with propensity for myeloid malignancy and neoplasms. Semin Hematol. 2017;54(2): CONCLUSIONS germline RUNX1 mutation. Haematologica. 81–86. Translation to improving familial 2017;102(10):1661–1670. 24. University of Chicago Hematopoietic myeloid malignancy predisposition 10. Sebert M, Passet M, Raimbault A, et al. Malignancies Cancer Risk T. How I diagnose Germline DDX41 mutations define a and manage individuals at risk for inherited assessments and syndrome-specific care significant entity within adult MDS/AML myeloid malignancies. Blood. 2016;128(14): for all patients in diverse, real-world, patients. Blood. 2019;134(17):1441–1444. 1800–1813. international clinical practice settings will 11. Borate U YF, Press RD, Pavlick D, Juckett L, 25. Luo X, Feurstein S, Mohan S, et al. ClinGen take major efforts to improve access, Agarwal A, et al. Prevalence of Inherited Myeloid Malignancy Variant Curation Expert education, clinical tools, policy, and Cancer Predisposition Mutations in a Cohort Panel recommendations for germline collaboration. Forward progress on many of Older AML Patients Enrolled on the BEAT RUNX1 variants. Blood Adv. 2019;3(20): AML Master Trial. Blood. 2019;134:373. 2962–2979. of these areas is noticeable and provides 12. Clinicaltrials.gov (https://clinicaltrials.gov/ 26. Cheah JJC, Hahn CN, Hiwase DK, Scott HS, hope that we will reach a future where ct2/show/NCT02775383?term=NCT0277 Brown AL. Myeloid neoplasms with germline prevention of MDS/AML is possible. 5383&draw=2&rank=1); Accessed 2/23/20. DDX41 mutation. Int J Hematol. 2017; 13. Padron E, Ball MC, Teer JK, et al. Germ line 106(2):163–174. REFERENCES tissues for optimal detection of somatic 27. Ogawa S. Genetics of MDS. Blood. 2019; variants in myelodysplastic syndromes. 133(10):1049–1059. 1. Arber DA, Orazi A, Hasserjian R, et al. The Blood. 2018;131(21):2402–2405. 2016 revision to the World Health 28. Drazer MW, Kadri S, Sukhanova M, et al. Organization classification of myeloid 14. Lewinsohn M, Brown AL, Weinel LM, et al. Prognostic tumor sequencing panels frequently neoplasms and acute leukemia. Blood. Novel germ line DDX41 mutations define identify germ line variants associated with 2016;127(20):2391–2405. families with a lower age of MDS/AML onset hereditary hematopoietic malignancies. and lymphoid malignancies. Blood. 2016; Blood Adv. 2018;2(2):146–150. 2. Baliakas P, Tesi B, Wartiovaara-Kautto U, et 127(8):1017–1023. al. Nordic Guidelines for Germline 29. Churpek JE, Pyrtel K, Kanchi KL, et al. Predisposition to Myeloid Neoplasms in 15. Polprasert C, Schulze I, Sekeres MA, et al. Genomic analysis of germ line and somatic Adults: Recommendations for Genetic Inherited and Somatic Defects in DDX41 in variants in familial myelodysplasia/acute Diagnosis, Clinical Management and Follow- Myeloid Neoplasms. Cancer Cell. 2015; myeloid leukemia. Blood. 2015;126(22): up. Hemasphere. 2019;3(6):e321. 27(5):658–670. 2484–2490. 3. Network NCC. Myelodysplastic Syndromes. 16. Polprasert C, Takeda J, Niparuck P, et al. 30. Li ST, Wang J, Wei R, et al. Rare germline National Comprehensive Cancer Network Novel DDX41 variants in Thai patients with variant contributions to myeloid malignancy Guidelines in Oncology. Version 1.2020. myeloid neoplasms. Int J Hematol. 2020; susceptibility. Leukemia. 2020. 111(2):241–246. 4. Kennedy AL, Shimamura A. Genetic 31. Genovese G, Jaiswal S, Ebert BL, McCarroll predisposition to MDS: clinical features and 17. Takeda J YK, Makishima H, Yoshizato T, SA. Clonal hematopoiesis and blood-cancer clonal evolution. Blood. 2019;133(10): Shiozawa Y, et al. Genetic Predispositions to risk. N Engl J Med. 2015;372(11): 1071–1085. Myeloid Neoplasms Caused by Germline 1071–1072. DDX41 mutations. Blood. 2015;126. 5. Tawana K, Drazer MW, Churpek JE. 32. Sanders MA, Chew E, Flensburg C, et al. Universal genetic testing for inherited 18. Tawana K, Wang J, Renneville A, et al. MBD4 guards against methylation damage susceptibility in children and adults with Disease evolution and outcomes in familial and germ line deficiency predisposes to myelodysplastic syndrome and acute AML with germline CEBPA mutations. Blood. clonal hematopoiesis and early-onset AML. myeloid leukemia: are we there yet? 2015;126(10):1214–1223. Blood. 2018;132(14):1526–1534. Leukemia. 2018;32(7):1482–1492. 19. Ganapathi KA, Townsley DM, Hsu AP, et al. 33. Xia J, Miller CA, Baty J, et al. Somatic 6. Sandner AS, Weggel R, Mehraein Y, GATA2 deficiency-associated bone marrow mutations and clonal hematopoiesis in Schneider S, Hiddemann W, Spiekermann K. disorder differs from idiopathic aplastic congenital neutropenia. Blood. 2018; Frequency of hematologic and solid anemia. Blood. 2015;125(1):56–70. 131(4):408–416. malignancies in the family history of 50 20. Wlodarski MW, Hirabayashi S, Pastor V, et patients with acute myeloid leukemia –a al. Prevalence, clinical characteristics, and

6 MEETING HIGHLIGHTS AND ANNOUNCEMENTS

62ND ASH ANNUAL MEETING & EXPOSITION • DECEMBER 4, 2020 • SAN DIEGO CONVENTION CENTER, SAN DIEGO, CALIFORNIA

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Our professional MDS Symposium at the American Society of Hematology Conference – A great start!!

BREAKFAST SYMPOSIUM PRECISION HEMATOLOGY IN MYELODYSPLASTIC SYNDROMES DECEMBER 6, 2019 7:00 – 11:00 am Orange County Convention Center Orlando, Florida

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7 2ND REGIONAL SYMPOSIUM ON MDS – ISRAEL 2020

THANK YOU TO ALL WHO ATTENDED!

THE PRESENTATIONS ARE NOW AVAILABLE ON OUR WEBSITE AT: https://www.mds-foundation.org/professional-learning-center/#2ndregionalsymposium

UPCOMING MEETING

XVI URUGUAYAN HEMATOLOGY CONGRESS 28 – 30 OCTOBER 2020

RADISSON HOTEL MONTEVIDEO – URUGUAY OCTOB ER 28, 2020 Second Lan American MDS Foundaon Symposium toge ther with the VII LaPn-AOme riScanT MyPe lodOysplaNscE SynDdromes (GLAM) Symposium. TO SEPTEMBER 1, 2021 OCTOBER 29–30, 2020 XI Uruguayan He matology Congress CONTACTS se cre tar [email protected]

8 MDS FOUNDATION INTERNATIONAL WORKING GROUP FOR PROGNOSIS IN MDS

LATEST NEWS REGARDING THE MOLECULAR MUTATION PROJECT OF THE IWG-PM

IWG-PM/MOLECULAR PROJECT recognition of SF3B1-mutant MDS as a In patients with MDS, TP53 mutations distinct nosologic entity. To further validate associate with high-risk presentation, this, Dr. Malcovati and colleagues complex karyotype, acute myeloid interrogated the dataset of the IWG-PM. leukemia (AML) progression and poor Based on these findings, the following response to hematopoietic stem cell diagnostic criteria for the MDS with transplantation. These findings highlight mutated SF3B1 was proposed as a the relevance of TP53 as a prognostic and distinct MDS subtype: (i) cytopenia predictive biomarker. Despite the central defined by standard hematologic values; role of TP53 in MDS, the clinical (ii) somatic SF3B1 mutation; (iii) isolated implications of TP53 mutations in the erythroid or multilineage dysplasia; (iv) context of allelic state have not been an independent prognostic factor for the presence of any ring sideroblasts; (v) extensively studied. Under the auspices of overall survival and AML transformation, bone marrow blasts <5% and peripheral 3 the International Working Group for whilst mono-allelic TP53 state was not. blood blasts <1%. Prognosis in MDS Molecular project Mono-allelic TP53 patients had more IWG-PM: THERAPY-RELATED (IWG-PM/Molecular) investigational efforts favorable disease than multi-hit TP53 MDS PROJECT generated data from which an abstract patients and were enriched in low risk In the current WHO classification, was presented at the ASH 2019 meeting WHO subtypes. Critically, multi-hit TP53 therapy-related Myelodysplastic Syn- describing results obtained from sequencing associated with worse overall survival as dromes (t-MDS) are placed together with marrow or blood samples from a compared to mono-allelic TP53 and with therapy-related Acute Myeloid Leukemia representative cohort of 3,324 peri- more pronounced AML transformation. (t-AML) and Myeloproliferative Neoplasms diagnosis MDS patients on a next These findings indicated that TP53 status (t-MPN) into one subgroup (t-MN) inde- generation sequencing (NGS) panel along is a critical candidate for incorporation pendent of morphological or prognostic with a validation cohort from a Japanese into molecularly informed risk stratification features. Drs Kuendgen, Nomdedue, MDS sample compendium.1 schemas (molecular IPSS-R). Thus, TP53 Tuechler and colleagues have assembled Data analysis of this study segregated mutation state is important for MDS risk a database including 2,087 t-MDS patients into two TP53 states: a mono- estimation, disease monitoring and future patients from different international MDS allelic state where one wild type allele correlative research. groups to evaluate current classification remained (33% of TP53 mutated patients, The IWG-PM/Molecular group project and prognostic tools.4,5 Cytogenetic data n=126); and a multi-hit state where TP53 is ongoing with plans for further was reviewed and strict selection criteria was altered multiple times by either development of a global classification with regard to completeness were mutations, deletions or cnLOH (67% of schema for MDS (IPSS-R/molecular). This applied. They analyzed and compared TP53 mutated patients, n=254). The issue was further discussed at the MDS 1,245 t-MDS patients to 4,593 primary findings demonstrated that TP53 state Foundation Symposium at ASH 2019.2 MDS (p-MDS) patients represented in was associated with clinical presentation the IWG-PM database. These data and outcomes. Mono-allelic TP53 SF3B1 MUTATED MDS AS A DISTINCT demonstrated that the IPSS-R and WPSS-R mutation patients presented with more DISEASE SUBTYPE PROJECT separated t-MDS patients into differing favorable disease than multi-hit TP53 A large body of evidence indicates risk groups effectively and indicated that mutated patients. Using multivariate that in MDS, the SF3B1 mutation is closely all established prognostic risk factors models that considered age, peripheral associated with ring sideroblasts and for p-MDS maintained relevance for t- blood counts, blasts and IPSS-R ineffective erythropoiesis and is MDS, with cytogenetic features having cytogenetic score, multi-hit TP53 mutation characterized by less aggressive clinical enhanced predictive power. Poorer state rather than the mutation alone was course. The available evidence supports clinical outcomes occurred in each t-MDS

9 MDS FOUNDATION INTERNATIONAL WORKING GROUP FOR PROGNOSIS IN MDS compared to p-MDS subgroups. Despite t- Bowen D, Campbell PJ, Ebert BL, Fenaux MDS being considered as having a P, Haferlach T, Heuser M, Jansen J, Komrokji RS, Maciejewski JP, Walter MJ, uniformly poor prognosis these data Fontenay M, Garcia-Manero G, demonstrated differing outcomes for each t- Graubert T, Karsan A, Meggendorfer M, Revised International Prognostic Scoring System (IPSS-R) for MDS subgroup. Given these data, these Pellagatt A, Sallman D, Savona MR, Myelodysplastic Syndromes findings suggest the ability and need for Sekeres MA, Steensma D, Tauro S, Thol Risk Assessment Calculator F, Vyas P, van de Loosdrecht A, Haase classifying t-MDS as a separate entity and D, Tuechler H, Greenberg PL, Ogawa S, distinct from the other WHO classified t- Hellstrom-Lindberg E, Cazzola M. myeloid neoplasms (t-MNs). This termin- SF3B1-mutant myelodysplastic syndrome ology would enable more reasonable treat- as a distinct disease subtype –A Proposal of the International Working © MDS Foundation. All rights reserved. ment decisions and facilitate the inclusion Group for the Prognosis of of t-MDS patients into clinical studies. Myelodysplastic Syndromes (IWG-PM). Blood 2020, in press. REFERENCES 4. Kuendgen A, Tuechler H, Nomdedeu M, 1. Bernard E, Nannya Y, Saiki R, et al. et al. Therapy-related MDS can be TP53 State Dictates Genome Stability, separated into different risk-groups This global project is being coordinated by Clinical Presentation and Outcomes in according to tools for classification and MDS, Proc Am Soc Hematology 2019, prognostication of primary MDS. Proc Ben Ebert and Peter Greenberg (co-Chairs), Orlando, December. Blood. 2019;134 ASH, San Diego, December 2018, Rafael Bejar and Ellie Papaemmanuil, with (Supplement_1):675. #3103. statistical support by Donna Neuberg, 2. Papemmanuil E, Classification and 5. Nomdedeu M, Tuechler H, Kuendgen A, Kristin Stevenson and Heinz Tuechler. personalized prognosis in MDS. MDS et al. Cytogenetic findings in therapy- Foundation Symposium, ASH meeting, related MDS – relation with primary 2019 Orlando, December. disease and therapy. Proc MDS 3. Malcovati L, Stevenson K, Papaemmanuil Foundation Symposium, Copenhagen, E, Neuberg D, Bejar R, Boultwood J, May 2019.

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THE MDS/MPN INTERNATIONAL WORKING GROUP develop new biomarkers for response to therapy, and augment efforts of large scale prospective genotyping efforts in MDS/MPN. This infrastructure will allow for ABNL-MARRO-002, -003, and so on, to quickly offer new therapies to patients with MDS/MPN.

WWW.MDSDIAGNOSIS.COM YOU GET FREE MEDICAL EDUCATION AFTER FREE REGISTRATION

OUR PROVIDED BY LANGUAGE MICHAEL SAVONA OFFER GLOBAL LEADING MDS EXPERTS MODULE Vanderbilt University Medical Center DIAGNOSIS: Dr. Ulrich Germing Dr. Esther Olivia English Nashville, Tennessee 7 lessons Dr. John Bennett Dr. Michael Pfeilstöcker German The first investigator driven, multi- 6 courses Dr. Detlef Haase Dr. Guido Kobbe French national MDS/MPN-specific trial in the 8 patient profiles Dr. Arjan van de Loosdrecht Dr. Rafael Bejar Spanish world is led by the MDS/MPN IWG. Dr. Raphael Itzykson Dr. Sophia Park Portuguese ABNL MARRO – ABasket Trial of THERAPY: Dr. Leonie Sa Dr. Blanca Xicoy Italian NoveL therapy combinations in untreated 6 lessons Dr. Fransesc Sole MDS/MPN And Relapsed/Refractory Dr. Alan F. List Overlap Syndromes (ABNL-MARRO) – is an international study designed to quickly test new compounds and combinations of therapy at referral centers within the YOU HAVE THE MDS/MPN IWG which see MDS/MPN patients, study the biology and OPPORTUNITY TO GIVE pathophysiology of the diseases, and have multilateral expertise in this area. US FEEDBACK ABNL MARRO-001 is the first MDS/ MPN IWG study and has been approved by the FDA. ABNL MARRO-001 uses an oral DNA methyltransferase inhibitor (DNMTi), ASTX727, as a backbone with YOU HAVE THE combination therapies targeting JAK1, OPPORTUNITY TO PIM kinase and LSD-1. DNMTi combinations have been evaluated in COMMUNICATE WITH KOL phase 1 safety studies, and will form 3 separate arms in ABNL MARRO-001. With ABNL MARRO-001, the MDS/MPN IWG aims to validate the proposed CME POINTS FOR DIAGNOSIS COURSES AND PATIENT PROFILES criteria for response in MDS/MPN, test WWW.MDSDIAGNOSIS.COM QOL tools in patients with MDS/MPN,

11 DO YOU KNOW YOUR MDS SUBTYPE AND IPSS-R SCORE? We launched a recent survey which showed that only 50% of patients know their subtype and only about 30% know their IPSS-R Score. Your subtype and IPSS-R score determine your personalized treatment plan. Knowing your subtype and IPSS-R score can help guide discussions with your doctor.

KNOWLEDGE IS POWER www.mds-foundation.org

ASK YOUR HEALTHCARE TEAM...

Knowing your IPSS-R score and

MDS subtype can guide discussions

with your healthcare team about the

best treatment options for you!

KNOW YOUR SCORE

The IPSS-R is a classification system used by doctors to help predict a person’s risk of developing AML and overall survival without treatment.

CATEGORIES & SCORES Very Low ...... ≤1.5 Low ...... >1.5 - 3 Intermediate ...... >3 - 4.5 High ...... >4.5 - 6 Very High ...... >6

KNOW YOUR SUBTYPE

MDS is classified into several FAB SUBTYPES WHO SUBTYPES different subtypes based on the Refractory Anemia (RA) MDS with single lineage dysplasia following features: Refractory Anemia with MDS with ring sideroblasts (MDS-RS)

• Blood cell counts Ringed Sideroblasts (RARS) MDS-RS and single lineage dysplasia

• Percentage of blasts in the Refractory Anemia with MDS-RS and multilineage dysplasia

Excess Blasts (RAEB) MDS with multilineage dysplasia bone marrow Refractory Anemia with MDS with excess blasts • Cytogenetics Excess Blasts in Transformation (RAEB-t) MDS with isolated del(5q) Chronic Myelomonocytic Leukemia (CMML) MDS, unclassifiable Acute Myeloid Leukemia (AML) Provisional entity: Refractory cytopenia of childhood

More detailed information on IPSS-R scores and subtype can be found online in our Building Blocks of Hope resource.

12 MDS FOUNDATION LEADERSHIP BOARD OF DIRECTORS Pierre Fenaux, MD Stephen D. Nimer, MD, Chair Charlotte M. Niemeyer, MD Hôpital St Louis, Université Paris 7 Sylvester Comprehensive Cancer Center Freiburg, Germany Peter L. Greenberg, MD Michael Savona, MD Franz Schmalzl, MD, Innsbruck, Austria Stanford University School of Medicine Vanderbilt University School of Medicine Sandra E. Kurtin, PhD, ANP-C, AOCN MEMBERS EMERITUS OFFICERS The University of Arizona Cancer Center John M. Bennett, MD Stephen D. Nimer, MD, Chair Alan F. List, MD Rochester, New York Tracey Iraca, Executive Director Tampa, Florida Sandra E. Kurtin, PhD, ANP-C, AOCN, Luca Malcovati, MD Eva Hellström-Lindberg, MD, PhD Treasurer University of Pavia School of Medicine Stockholm, Sweden Janice Butchko, Secretary MEDICAL AND SCIENTIFIC ADVISORY BOARD Rafael Bejar, MD, PhD Silvia M. M. Magalhães, MD, PhD DEVELOPMENT BOARD Moores Cancer Center Federal University of Ceará Stuart Goldberg, MD at the University of California, San Diego Hospital Universitário Walter Cantídio John Theurer Cancer Center at Hackensack Rena Buckstein, MD, FRCPC Moshe Mittelman, MD University Medical Center, MDS Specialist Sunnybrook Health Sciences Centre Tel-Aviv Sourasky Medical Center Jennifer Keam, MD, MPH Mario Cazzola, MD, Chair Yasushi Miyazaki, MD MDS Caregiver University of Pavia School of Medicine Nagasaki University Deborah Peirce, Chair Fondazione IRCCS Policlinico San Matteo Ghulam J. Mufti, DM, FRCP, FRCPath Talent/Leadership and Organizational Jane Churpek, MD, MS King’s College London & King’s College Hospital Development Executive, MDS Caregiver UW Carbone Cancer Center Seishi Ogawa, MD, PhD Julia McGuire, Advisor University of Wisconsin Kyoto University Executive Vice President, Campbell & Company School of Medicine and Public Health Uwe Platzbecker, MD Madeleine’s Mom, MDS Patient Theo J.M. de Witte, MD, PhD Universitätsklinikum Carl Gustav Carus Radboud University Nijmegen Medical Centre Guillermo Sanz, MD Nijmegen Centre of Molecular Life Sciences Hospital Universitario y Politecnico La Fe Erin P. Demakos, RN, CCRN Akiko Shimamura, MD, PhD Icahn School of Medicine at Mount Sinai Dana-Farber Cancer Institute Benjamin Ebert, MD, PhD Lewis R. Silverman, MD Dana-Farber Cancer Institute Icahn School of Medicine at Mount Sinai INTERNATIONAL NURSE LEADERSHIP BOARD Erik Aerts, RN Lenn Fechter, RN Geke Ong, RN Zürich, Switzerland Stanford, California, United States London, United Kingdom Angelika Bitter Janet Hayden, RN, BSc(hons), MPH Phyllis Paterson, RN, RSCN, Dip Onc Dresden, Germany London, United Kingdom Cambridge, United Kingdom Claudia Boglione, RN Amelia Hodson, BSN, RN, Clinician II Jean A. Ridgeway, DNP, APN, NP-C, AOCN Florence, Italy Charlottesville, Virginia, United States Chicago, Illinois, United States Karen Campbell, RN Miki Iizuka, RN Natalie Singer, MSc, RN, BSc(Hons) Edinburgh, Scotland, United Kingdom Tokyo, Japan Glasgow, Scotland, United Kingdom Hwang Chung Cheng Jordan Jacqueline Jagger, BA, RN Samantha Soggee, RN, MN Singapore Gosford, Australia Heidelberg, Victoria, Australia Nancy Corbitt BSN, RN, OCN, CRNI Natasha L. Johnson, MS, APRN, AOCNP Amber Thomassen, AGPCNP-BC, AOCNP Baltimore, Maryland, United States Tampa, Florida, United States Miami, Florida, United States Nicole Crisp, RN, BScN, MN, NP-adult Sandra E. Kurtin, PhD, ANP-C, AOCN Sara M. Tinsley, PhD, ARNP, AOCN Edmonton, Alberta, Canada Tucson, Arizona, United States Tampa, Florida, United States Lucy Cussans, RN Petra Lindroos Kolqvist, RN Catherine Vassili, RN, MN North Terrace, Adelaide, Australia Goteborg, Sweden Victoria, Australia Erin Demakos, RN, CCRN Arno Mank, RN, PhD Lauren Ziskind, MSN, NP-C, FNP-BC, OCN New York, New York, United States Amsterdam, The Netherlands Chicago, Illinois, United States Rebecca Dring, RN R. Denise McAllister, MS, ARNP, AOCNP Melbourne, Australia Clearwater, Florida, United States Corien Eeltink, RN, MA ANP Cindy Murray, RN, MN, NP-adult Amsterdam, The Netherlands Toronto, Ontario, Canada

13 MDS AWARENESS

MDS AWARENESS WALK – JOIN US AND RUN/WALK WITH PURPOSE!

the myelodysplastic syndromes foundation, inc. POSTPONED – SPRING MDS AWARENESS WALKS Dear Friends of the MDS Foundation, We understand that during the uncertainty of this pandemic, the main concern of all is protecting yourself as well as your families and friends from exposure to the COVID-19 virus. The highest priority of A HEARTFELT THANKS TO ALL OF the MDS Foundation at this time, and always, is the health and safety OUR WALKERS, VOLUNTEERS AND of our community. With this in mind, and in consultation with medical professionals, we have decided to postpone our upcoming MDS SPONSORS FOR MAKING OUR Awareness Walks in Chicago and New York City. We are waiting for WALKS A HUGE SUCCESS! permits to be finalized, but we are hoping to reschedule the walks for early Fall. Look to our website and facebook for updates on our MDS Awareness Walks which may be going virtual due to the coronavirus pandemic. We can’t come together as a community in person, but that doesn’t mean we can’t make a difference individually. This situation is continuously evolving and we will evaluate any further developments as they come. We will send out another email once we have confirmed the new dates. In the meantime, should you want to support the walks or set up a team, please visit https://www.mds- foundation.org/mds-awareness-walk/. We appreciate your continued support and thank you for understanding as we navigate the current situation. Check our website and facebook for updates Best wishes during this difficult time. on our 2020 events in Boston, Chicago, Nashville, and New Jersey/New York and Tracey Iraca, Executive Director save the date for the location nearest you!!

14 MDS RESOURCES

LITERATURE HIGHLIGHTS

HIGHLIGHTS OF LATEST LITERATURE IN MDS SUNEEL D. MUNDLE, PHD RHEA MUNDLE Listed below are citations of some new publications relevant to MDS (pathogenesis, clinical characterization, management, etc.). To access the complete articles log on to www.pubmed.gov.

EPIDEMIOLOGY, DIAGNOSIS AND PROGNOSIS: Data on 47 men and 37 women aged remained as a significant covariate of 1. Liang S, et al. Prognostic value of 85 yrs demonstrated that 93% patients OS in a multivariate analysis as well. DNMT3A mutations in myelodysplastic ≥ were anemic at diagnosis with a med Additionally, FI discriminated OS within syndromes: a meta-analysis. Hematology, Hb level of 9.5g/dL. Sixty four percent each of the IPSS-/-R categories. 2019;24(1):613–622. (https://pubmed. of patients had more than one ncbi.nlm.nih.gov/31482762/) TREATMENT: cytopenia, 53% patients had elevated The meta-analysis included 12 studies serum ferritin levels, and 88% patients RBC Transfusion and Growth Factors: with 2236 MDS patients. A pooled HR had one or more significant comorbid- 1. Stanworth SJ, et al. Red cell transfusion for overall survival and leukemia free ities (cardiac, renal, or diabetes). Of the in outpatients with myelodysplastic survival showed significantly adverse patients with significant anemia (Hb syndromes: A feasibility and exploratory prognostic impact of DNMT3A randomized trial. Br J Haematol, 2020; mutations, (OS- HR-1.65, p<0.001; <10 g/dL), 42% received erythro- Jan 20 [Online ahead of print]. LFS- HR-4.62, p<0.001) poietin. Of the 29 transfusion- dependent patients only 48% received (https://pubmed.ncbi.nlm.nih.gov/ 2. Kurumaddali A, Salem AH and erythropoietin. The AML transformation 31960409/) Agarwal AK. Spanish guidelines for the rate was 7%. The median overall use of targeted deep sequencing in This multinational study randomized 38 survival was 16 mo in men and 27 mo myelodysplastic syndromes and chronic patients in outpatient clinic to initiate myelomonocytic leukemia. J Cancer, in women. In 34 patients with IPSS-R RBC transfusion at standard threshold 2019;10(22):5427–5433. (https:// classification, the med survival was of Hb ≤8.0 g/dL (n=20) vs a liberal pubmed.ncbi.nlm.nih.gov/31632487/) 31.5 mo in very good risk, 41.5 mo in threshold of Hb ≤10.5 g/dL (n=18). good risk, and 8mo in int risk patients. Using a pre-established clinical trial The compliance for transfusion database and linear regression 4. Starkman R, et al. An MDS-Specific threshold was 86% vs 99% in the analysis of 25 trials with 38 cohorts, frailty index based on cumulative standard vs liberal groups and the deficits adds independent prognostic mean pre-transfusion Hb was 8.0 g/dL the authors found that ≥PR (PR+CR+Marrow CR) was a strong information to clinical prognostic and 9.7 g/dL respectively. Using predictor of OS (adjusted R2=0.64). scoring. Leukemia, 2019:Dec 6 EORTC QLQ-C30 and EQ-5D-5L tools, Furthermore, for a given response rate [Online ahead of print]. (https:// the quality of life was found to be better pubmed.ncbi.nlm.nih.gov/31811236/) in patients on liberal Hb threshold arm. (≥PR) or treatment group, the survival was longer in treatment naïve vs A frailty Index (FI) based on impact of 2. de Swart L, et al. Impact of red blood previously treated patients. deficits on likelihood of adverse cell transfusion dose density on 3. McDonald LS, et al. A multicenter outcomes was calculated in 440 MDS progression free survival in lower-risk report on the natural history of patients. The median FI was 0.25 and myelodysplastic syndromes patients. myelodysplastic syndromes in very old FI was correlated with age, IPSS-/-R Haematologica, 2020;105(3):632–639. patients (aged over 85 years). Leuk risk. The FI ≤0.2 vs >0.2-0.3 vs >0.3 (https://pubmed.ncbi.nlm.nih. Lymphoma, 2019; 60(5):1324–1327. demonstrated significantly different OS gov/31171638/) (https://pubmed.ncbi.nlm.nih.gov/30 with a median 55.6 mo, 24 mo and The analysis based on European MDS 632846/) 10.9 mo respectively (p<0.0001). FI registry included 1267 lower risk MDS

15 LITERATURE HIGHLIGHTS

patients: 317 had died without Lymphoma, 2020; Feb 8 [Online lower hematologic toxicity (Gr3/4 progression and 162 had disease ahead of print]. (https://pubmed. neutropenia – 60% vs 88%; thrombo- progression. When assessed for the ncbi.nlm.nih.gov/32036719/) cytopenia – 65% vs 88% respectively). impact of blood transfusions on overall The Ontario AZA-MDS registry linked to Additionally, the report also found that progression-free survival (PFS), the population based administrative the overall survival benefit with 15 mg/ transfusion density as low as 3 databases showed approx. 80% m2/day was primarily associated with units/16 weeks was associated with patients (705/877) had at least one lower risk patients. poorer PFS that continued to increase emergency clinic visit; 33% in their first 4. Ades L, et al. A phase II study of beyond 8 units/16 weeks. cycle. Also, approx. 77% had at least efficacy and safety of an intensified 3. Kaphan E, et al. Impact of transfusion on one hospitalization with a mean length schedule of azacytidine in intermediate- survival in patients with myelodysplastic approx. 18 days. A greater comorbid- 2 and high-risk patients with syndromes: current knowledge, new ity, non-response to AZA and transfusion myelodysplastic synromes: A study by insights and transfusion clinical practice. dependence were associated with both the Groupe Francophone Des Blood Rev, 2019; Dec 18 [Online emergency room visits and hospitali- Myelodysplasies (GFM). Heamatologica, ahead of print]. (https://pubmed. zations. Also, among patients with ≥3 2019;104(4):e131–e133. (https:// ncbi.nlm.nih.gov/31918886/) cycles of treatment hospitalization pubmed.ncbi.nlm.nih.gov/30381302/) Patients treated with red blood cell during first cycle was associated with An azacytidine treatment intensification (RBC) transfusions experience shorter an increased risk of death. tested using a schedule leading to 20% survival as compared to those treated 2. Chandhok N, et al. Hypomethylating higher number of days with azacytidine with erythropoiesis stimulating agents agent-based combinations in higher (75 mg/m2/day x 5 days in 14-day (ESAs). The report has attempted to list risk myelodysplastic syndrome. Leuk cycle) administration during first 8 the physiologic impacts of chronic RBC Lymphoma, 2019; Dec 9 [Online weeks of treatment. Patients who transfusion strategy highlighting iron ahead of print]. (https://pubmed.ncbi. achieved CR/PR received additional toxicity, cardiac event rate, oxidative nlm.nih.gov/31814484/) aza at 21-day cycles x 4 followed by stress and RBC storage lesions due to The authors argue that there continues std 7-day dosing in a 28-day cycle until physicochemical changes in RBCs. to exist an unmet need to improve progression. For patient not achieving 4. Swaminathan M, et al. A phase 2 upfront treatment of higher risk MDS CR or PR after first 8 weeks, additional clinical trial of eltrombopag for treatment patients as only a proportion of patients 8 weeks of intensified treatment was of patients with myelodysplastic respond to hypomethylating agents and given. The primary end point was syndromes after hypomethylating agent the responses are less durable. Authors response by IWG 2006 criteria after failure. Leuk Lymphoma, 2019; propose upfront combinations with first 4 and 8 dose intensified cycles (15- 60(9):2207–2213. (https://pubmed. other agents as a way to improve day cycles). The int-2- and high-risk ncbi.nlm.nih.gov/30773968/) outcomes of HMA and list venetoclax proportions were 65:35 among the 26 Eltrombopag was given at a starting and rigosertinib as promising agents evaluable patients. The overall marrow dose of 200mg orally per day either as for such combination. response after 4- or 8-weeks intensified monotherapy (n=7) or was added to 3. Ren Y, et al. Decitabine for treatment was 22% (6/27). The HMA (n=22) after the failure of initial myelodysplastic syndromes: Dose marrow CR+ hematologic improvement HMA therapy of high risk MDS. There comparison in a real world clinical (HI) was 65% after week 4 and 62% was one early death (<30 days) due to setting. Leuk Lymphoma, 2019;60(7): after week 8. With a f/u of approx. 42 infection/sepsis, an overall 11% 1731-1739. (https://pubmed.ncbi. mo, median duration of CR/PR was (3/28) platelet improvement rate and a nlm.nih.gov/30616472/) 10.5 mo, duration of overall response med survival of 12 mo. Addition of This was a retrospective study with 133 was 14 mo, and overall survival was eltrombopag to HMA did not show MDS patients. The study demonstrated 21.5 mo. Treatment intensification was additive toxicity. that in real world patients 15 mg/ not associated with increased toxicity. Hypomethylating Agents: m2/day dose vs. 20mg/m2/day dose 5. Zeidan A, et al. Treatment sequence of 1. Mozessohn L, et al. Healthcare resulted in a comparable response rates lenalidomide and hypomethylating utilization in patients with higher-risk (ORR-51.8% vs 52%, CR-15.7% vs agents and the impact on clinical MDS/low-blast count AML treated with 22% respectively), longer survival outcomes for patients with myelodys- azacytidine in the real-world. Leuk (21.6 mo vs 15.2 mo respectively), and plastic syndromes. Leuk Lymphoma,

16 LITERATURE HIGHLIGHTS

2019;60(8):2050–2055. (https:// PATHOBIOLOGY: REVIEWS, PERSPECTIVES pubmed.ncbi.nlm.nih.gov/30636526/) 1. Elvarsdóttir EM, et al. A three & GUIDELINES: A US claims database study (Inovalon dimensional in vitro model of erythro- The following articles provide significant MORE2 registry) comparing outcomes poiesis recapitulates erythroid failure in review of literature and/or innovative of treatment sequence Len- HMA vs myelodysplastic syndromes. Leukemia, perspective on the state-of-the-art in MDS or HMA-Len demonstrated longer time to 2020;34(1):271–282. (https://pubmed. discuss therapeutic management guide- discontinue second treatment (HR-0.52, ncbi.nlm.nih.gov/31375745/) lines and identify need for additional p=0.023), and to disenroll from Using a modified scaffolding of prospective studies. insurance used as proxy for survival collagen coated polyurethane 3D 1. Fenaux P, Platzbecker U and Ades L. (HR-0.64, p=0.017). cultures were established with How we manage adults with Novel Therapies: mononuclear cells (MNC) and CD34+ myelodysplastic syndrome. Br J 1. Sekeres M and Steensma D. Rethinking enriched bone marrow cells from Haematol, 2019; Sept 30 [Online clinical trial end points in myelo- healthy volunteers and MDS-RS patients. ahead of print]. (https://pubmed. dysplastic syndrome. Leukemia, 2019; Such 3D cultures supported proliferation ncbi.nlm.nih.gov/31568568/) and differentiation of erythroid cells 33(3):570-575. (https://pubmed.ncbi. 2. Fenaux P, Kiladjian J and Platzbecker from CD34+ cells and multilineage nlm.nih.gov/30700839/) U. Luspatercept for the treatment of growth from MNC for more than 4 The review evaluates challenges to anemia in myelodysplastic syndromes weeks. Importantly, the cultures drug development and emphasizes the and primary myelofibrosis. Blood, 2019; demonstrated significant erythroid meaningfulness of study end points 133(8):790–794. (https://pubmed. differentiation including erythroid relevant to patients. The report also ncbi.nlm.nih.gov/30602619/) islands and enucleated erythrocytes, underscores the importance of 3. Komrokji R. Luspatercept in preserved RS phenotype and the assessing longer term end points such myelodysplastic syndromes: Who and SF3B1mutated clone. This technology as response duration, quality of life and When?. Hematol Oncol Clin North could have significant implication in overall survival in addition to the Am, 2020;34(2):393-400. (https:// drug development for MDS. currently common end points of pubmed.ncbi.nlm.nih.gov/32089218/) hematologic and bone marrow 2. Behbehani GK, et al. Profiling 4. Santini V. How I treat MDS after response rates. myelodysplastic syndromes by mass cytometry demonstrates abnormal hypomethylating agent failure. Blood, PATIENT REPORTED OUTCOMES: progenitor cell phenotype and 2019;133(6):521–529. (https://pubmed.ncbi.nlm.nih.gov/3 1. Barot SV, Patel BJ, and Gerds AT. differentiation. Clin Cytometry, 2020; 0545832/) Patient-reported outcomes in myelo- 98:131–145. (https://pubmed.ncbi. 5. Komrokji R. Activin receptor II ligand dysplastic syndromes: the move from nlm.nih.gov/31917512/) traps: new treatment paradigm for life span to health span (MDS). Current A high-dimensional single cell mass low-risk MDS. Curr Hematol Malig Hematol Malig Rep, 2020; Feb 11 cytometry (MCM) in addition to Rep, 2019;14(4):346-351. (https:// [Online ahead of print] (https:// previously reported surface anomalies pubmed.ncbi.nlm.nih.gov/31203517/) pubmed.ncbi.nlm.nih.gov/32048198/) also detected increased CD321 and Although PRO measurement is less CD99 expression and decreased CD47 expression. In hematopoietic common in clinical studies in MDS, A special thanks to Suneel when conducted have demonstrated between MDS vs cytopenia of positive results with growth factors, HMS undetermined significance and finally and Rhea Mundle for their and IMiDs. Many new clinical studies the high-parameter MCM data great efforts in monitoring identified abnormal differentiation have begun to incorporate a prospective these important MDS PRO assessment using broad metrics patterns of myeloid cells that were such as EORTC-QLQ-C30, the previously immunophenotypically closer to peer-review publications. reported FACT-An and MDS specific myeloid derived suppressor cells. tools like QUALMS (Quality of life in Myelodysplasia Scale).

17 UPDATES IN MDS

MDS NEWS

ERYTHROPOIESIS AND RING SIDEROBLASTS: WHAT DOES THAT MEAN FOR MDS PATIENTS? overall are between 20 and 40%. Patients usually respond for 18–24 months. For patients with deletion of 5q, lenalidomide is the standard of care with a 67% response rate that normally lasts about 3 Ring Sideroblasts in MDS years.7 Various sites of differentiation have (courtesy of ASH image bank) been postulated for lenalidomide.8 syndrome. Blood 124(6):873–881. https: On April 3, the Food and Drug Admin- //doi-org.moffitt.idm.oclc.org/10.1182/ SARA M. TINSLEY, PHD, ARNP, AOCN istration approved luspatercept (REBLOZYL, blood-2014-03-563221 Malignant Hematology Celgene Corporation) for the treatment of 04. Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Solé F, Kantarjian, Nurse Practitioner anemia in adult patients with very low- to H. (2012). Revised international prognostic H. Lee Moffitt Cancer Center intermediate-risk myelodysplastic syndromes scoring system for myelodysplastic Tampa, Florida, United States with ring sideroblasts (MDS-RS) or with syndromes. Blood 120(12), 2454–2465. 05. Valent P, Busche G, Theurl I, et al. Normal Erythropoiesis is the term for producing red myelodysplastic/myeloproliferative neoplasm and pathological erythropoiesis in adults: blood cells from the hematopoietic stem cells with ring sideroblasts and thrombocytosis from gene regulation to targeted treatment to circulating mature red blood cells. This (MDS/MPN-RS-T) who have failed treatment concepts. Haematologica 2018;103:pp. 1593–1603. occurs in the bone marrow, and is quite a with erythroid stimulating agents and 06. Hellström-Lindberg E, Gulbrandsen N, complex process producing over 10 billion required 2 or more units of packed red blood Lindberg G, Ahlgren T, Dahl IMS, Dybedal red blood cells hourly under normal conditions cells in an 8-week period. Luspatercept I, Grimfors G, Hesse-Sundin E, Hjorth M, to maintain stable hemoglobin levels.1 In works further along in the pathway of red Kanter-Lewensohn L, Linder O, Luthman M, Löfvenberg E, Öberg G, Porwit-MacDonald myelodysplastic syndromes (MDS), erythro- blood cell development than prior A, Rådlund A, Samuelsson J, Tangen JM, poiesis is defective resulting in anemia; a treatments. In clinical trials, side effect profile Winquist I, Wisloff F, Group ftSM. (2003). hallmark of the disease.2 The majority of included fatigue, diarrhea, nausea, asthenia, A validated decision model for treating the anaemia of myelodysplastic syndromes patients diagnosed with MDS will become dizziness and back pain.9 Luspatercept is with erythropoietin+granulocyte colony- dependent on red blood cell transfusions.3 given subcutaneously every 3 weeks and is stimulating factor: significant effects on quality One of the goals of treatment with lower- dosed at 1 mg/kg. Response rates varied of life. Br J Haematol 120(6):1037–1046. https://doi-org.moffitt.idm.oclc.org/ risk MDS (LR-MDS), defined as very low, low, among the clinical trials for reduction in 10.1046/j.1365-2141.2003.04153.x or intermediate on the revised international number of red blood cells transfused. However, 07. List A, Dewald G, Bennett J, et al. prognostic scoring system (<3.5 points)4, is approximately 40% of patients experienced Lenalidomide in the myelodysplastic syn- drome with chromosome 5q deletion. New to minimize the number of red blood cell improvement with reduction in the number of England Journal of Medicine 2006;355: transfusions and improve quality of life. red blood cells needed. This is an exciting pp. 1456–1465. Current treatments for LR-MDS are time with a new treatment now available 08. Ebert BL, Galili N, Tamayo P, Bosco J, Mak for the treatment of anemia in MDS! R, Pretz J, Tanguturi S, Ladd-Acosta C, focused on treatment of anemia with recent Stone R, Golub TR, Raza A: An erythroid improvement in the understanding of REFERENCES differentiation signature predicts response ineffective erythropoiesis. There are two to lenalidomide in myelodysplastic 01. Zivot A, Lipton JM, Narla A, et al. syndrome. PLoS Med. 2008, 5(2):e35- areas of primary interest, early stage and Erythropoiesis: insights into patho- 10.1371/journal. pmed.0050035. a later stage, focused on terminal erythroid physiology and treatments in 2017. Mol 09. Fennaux P, Platzbecker U, Mufti G, et al. maturation into red blood cells.5 Erythroid Med 24, 11 (2018). https://doi.org/ The medalist trial: results of a phase 3, 10.1186/s10020-018-0011-z stimulating agents (ESAs), such as epoetin randomized, double blind, placebo- 02. Goasguen JE, Bennett JM, Bain BJ, controlled study of luspatercept to treat alfa and darbepoetin alfa, are frequently Brunning R, Vallespi MT, Tomonaga M, Zini anemia in patients with very low-, low-, or first-line treatment for anemia in LR-MDS, G, Renault A. (2018). Dyserythropoiesis in intermediate –risk Myelodysplastic Syn- targeted toward early stage erythropoiesis. the diagnosis of the myelodysplastic dromes (MDS) with Ring Sideroblasts (RS) syndromes and other myeloid neoplasms: Who Require Red Blood Cell (RBC) Specific criteria are used to determine problem areas. Br J Haematol, 182:526-533. transfusions. Blood 2018;132:pp1. patients who will likely benefit from ESAs. doi:10.1111/bjh.15435 10. FDA – US Food and Drug Administration Criteria include low transfusion burden (<2 03. Shenoy N, Vallumsetla N, Rachmilewitz E, retrieved 4/8/20 from https://www.fda. Verma A, Ginzburg Y. (2014). Impact of gov/drugs/resources-information- units per month) and an erythropoietin iron overload and potential benefit from approved-drugs/fda-approves-luspatercept- level < 500 u/L.6 Response rates to ESAs iron chelation in low-risk myelodysplastic aamt-anemia-adults-mds

18 CORD BLOOD REGISTRY

CORD BLOOD REGISTRY

Depending on the condition being treated, an HSC transplant are 1 in 217. When CORD BLOOD REGISTRY: the stem cells used in a transplant may come stored under the proper conditions, cord PROVIDING CORD BLOOD from a healthy donor or from the patient blood stem cells are expected to last BANKING TO FAMILIES themselves. In treating patients with MDS, indefinitely, providing a long-term resource IN NEED the stem cells typically come from a healthy for families’ potential use. donor, preferably a sibling who is a good As part of CBR’s commitment to families ELIZA STROH, MS, LCGC genetic match to the patient. Using stem cells in need, our Newborn Possibilities Program® Cord Blood Clinical Specialist from a closely matched relative helps to offers cord blood processing and 5 years at Cord Blood Registry improve transplant outcomes. of storage at no cost for families in which Cord blood is a rich source of blood Cord blood stem cells can be collected a parent or full sibling of the newborn is forming stem cells (called hematopoietic and stored at the time of birth and either diagnosed with a condition for which HSC stem cells or HSCs). For more than 20 years, donated to a public cord blood bank for use transplant may be a treatment option. This cord blood has been used as a source of by an anonymous patient in need or stored program provides families with access to a stem cells for patients requiring a stem cell in a private bank for potential use within the potential source of valuable stem cells, transplant as part of their treatment for bone family. Cord Blood Registry® (CBR®) is the should a transplant be required. To date, marrow failure conditions, like the largest and most experienced family cord CBR has enrolled more than 8,000 families myelodysplastic syndromes (MDS), as well blood bank. We offer cord blood collection, into the Newborn Possibilities Program. as other hematological diseases and processing and storage services to families Though MDS is typically diagnosed in malignancies. To date, more than 40,000 who wish to save their children’s cord blood individuals past child bearing age, families cord blood stem cell transplants have been at the time of birth for the family’s potential with MDS are eligible to apply for the performed worldwide. In transplant use in the future. By saving cord blood at the program. In addition, CBR has Genetic medicine, HSCs are used to regenerate the time of birth, families can ensure that they Counselors on staff to help families make patient’s blood and immune systems after have access to this important resource informed choices about their newborn stem chemotherapy and/or radiation treatments should anyone in the immediate family ever cell banking options and to answer have been given to suppress or ablate the require a HSC transplant. Many patients questions regarding medical indications patient’s own blood and immune systems. with hematological conditions, including for cord blood banking. Cord blood HSCs have advantages over MDS, have no family history of the other sources of HSCs, such as those condition, and therefore banking at the time For more information about Cord Blood derived from bone marrow, including a of birth provides a “safety-net” for families. Registry or the Newborn Possibilities lower risk of graft-vs-host disease, which can In fact, current estimates suggest that, over Program please call us at 1-888-cordblood be a serious side effect of HSC transplants. an individual’s lifetime, the odds of requiring or visit www.cordblood.com.

19 MDS CENTERS OF EXCELLENCE

Our MDS Centers of Excellence are institutions that meet the highest standards for diagnosis, treatment and patient care. These centers help patients seeking first or second opinions and/or additional treatment options from experts in MDS. We currently have 72 Centers in the United States and 112 Centers in countries around the world. Our MDS Centers can be viewed here: https://www.mds-foundation.org/mds-centers-of-excellence BENEFITS OF MEMBERSHIP: I MDSF CoEs form the referral base for the patients who contact the Foundation daily. I MDSF CoEs are proudly recognized on the Foundation website, within our printed newsletters, and through our various social media platforms. I MDSF CoEs are offered reduced registration rates at our Int’l Symposia and discounted subscription rates to Leukemia Research. I MDSF CoEs have full access to MDSF educational resources for distribution to your patients. I In addition, along with your $500 CoE renewal payment, your annual MDSF Professional Membership dues are waived. MDSF Professional Members are also listed, by name, on our website and in our printed newsletters. I The work of your institution can be shared with our patient and professional contacts via our website and/or our social media channels. We can spread the word of your clinical trials, research projects, etc.

Would you like your treatment center to become part of the referral system for MDS patients and be designated as a Center of Excellence? To be recognized as a Center of Excellence, an institution must have the following: I An established university I Available cytogenetics and/or molecular genetics I Documentation of peer-reviewed (or equivalent) program I Ongoing research, including Institutional Review publications in the field I Recognized morphologic expertise in MDS Board–approved clinical trials Please contact the Foundation for further information and an application form for your center. The following centers have qualified as MDS Centers of Excellence:

UNITED STATES UCLA Health Hematologic Malignancies University of Florida and Stem Cell Transplant Program Shands Hospital ALABAMA Los Angeles, California Gainesville, Florida University of Alabama at Birmingham Gary J. Schiller, MD Christopher R. Cogle, MD Birmingham Comprehensive Cancer Center University of Southern California Birmingham, Alabama GEORGIA Keck School of Medicine Kimo Bachiashvili, MD Los Angeles, California Emory Winship Cancer Institute Casey L. O’Connell, MD Emory University School of Medicine ARIZONA Atlanta, Georgia Mayo Clinic Hospital COLORADO Amelia Langston, MD Phoenix, Arizona University of Colorado School of Medicine Cecilia Arana Yi, MD/Lisa Sproat, MD The Blood and Marrow Transplant University of Colorado Cancer Center Aurora, Colorado Program at Northside Hospital The University of Arizona Cancer Center Atlanta, Georgia Daniel Aaron Pollyea, MD, MS Tucson, Arizona Asad Bashey, MD Ravi Krishnadasan, MD, FACP CONNECTICUT ILLINOIS Yale Cancer Center/Smilow Cancer Hospital CALIFORNIA Loyola University Chicago Cedars-Sinai Medical Center Yale University School of Medicine New Haven, Connecticut Cardinal Bernardin Cancer Center UCLA School of Medicine Maywood, Illinois Los Angeles, California Amer Zeidan, MD Scott E. Smith, MD, PhD H. Phillip Koeffler, MD FLORIDA Robert H. Lurie Comprehensive Cancer City of Hope National Medical Center Mayo Clinic Center of Northwestern University Duarte, California Jacksonville, Florida Feinberg School of Medicine Stephen J. Forman, MD James M. Foran, MD Chicago, Illinois Olga Frankfurt, MD Moores Cancer Center–UC San Diego Health Moffitt Cancer Center San Diego, California Tampa, Florida Rush University Medical Center Rafael Bejar, MD, PhD Rami Komrokji, MD Chicago, Illinois Peter Curtin, MD Jamile Shammo, MD Sylvester Comprehensive Cancer Center Stanford University Medical Center University of Miami, Miller School of Medicine University of Chicago Medical Center Stanford, California Miami, Florida Chicago, Illinois Peter L. Greenberg, MD Stephen D. Nimer, MD Richard A. Larson, MD

20 INDIANA MISSOURI University of Rochester Medical Center Indiana University Simon Cancer Center Washington University School of Medicine Rochester, New York Indianapolis, Indiana Siteman Cancer Center Jane L. Liesveld, MD Larry Cripe, MD/Hamid Sayar, MD, MS St. Louis, Missouri John F. DiPersio, MD, PhD Weill Medical College of Cornell University IOWA New York Presbyterian Hospital NEBRASKA New York, New York The University of Iowa Hospitals Gail J. Roboz, MD and Clinics, Holden Cancer Center University of Nebraska Medical Center Iowa City, Iowa Omaha, Nebraska Lori Maness, MD NORTH CAROLINA Carlos E. Vigil-Gonzales, MD Atrium Health Levine Cancer Center NEW HAMPSHIRE Charlotte, North Carolina KANSAS Dartmouth-Hitchcock Medical Center Srinivasa R. Sanikommu, MD, FACP The University of Kansas Cancer Center and Norris Cotton Cancer Center Michael Grunwald, MD Westwood, Kansas Lebanon, New Hampshire Barry Skikne, MD Kenneth R. Meehan, MD Duke University Medical Center Durham, North Carolina MARYLAND NEW JERSEY Carlos M. deCastro, MD Johns Hopkins University School of Medicine John Theurer Cancer Center at Baltimore, Maryland The North Carolina Cancer Hospital Hackensack University Medical Center Amy Elizabeth DeZern, MD Hackensack, New Jersey University of North Carolina Lineberger Stuart Goldberg, MD Comprehensive Cancer Center University of Maryland Chapel Hill, North Carolina Greenebaum Cancer Center Rutgers Cancer Institute of New Jersey Matthew Foster, MD/Brandi Reeves, MD Baltimore, Maryland Rutgers University Hematologic Malignancies Maria R. Baer, MD and Stem Cell Transplant Wake Forest University School of Medicine New Brunswick, New Jersey Comprehensive Cancer Center MASSACHUSETTS Dale G. Schaar, MD, PhD Winston-Salem, North Carolina Dana-Farber/Boston Children’s Cancer Bayard L. Powell, MD and Blood Disorders Center NEW MEXICO Boston, Massachusetts University of New Mexico OHIO Akiko Shimamura, MD, PhD Comprehensive Cancer Center Albuquerque, New Mexico Cleveland Clinic Foundation Dana-Farber Cancer Institute Leslie Andritsos, MD Taussig Cancer Center Boston, Massachusetts Cleveland, Ohio Richard M. Stone, MD/David P. Steensma, MD NEW YORK Jaroslaw Maciejewski, MD, PhD Benjamin Ebert, MD, PhD Albert Einstein Cancer Center/Albert Einstein Mikkael Sekeres, MD, MS Massachusetts General Hospital College of Medicine of Yeshiva University Bronx, New York Hoxworth Blood Center, George L. Strike Cancer Center Amit Verma, MD Bone Marrow Transplant Program Boston, Massachusetts University of Cincinnati – UC Health Timothy Graubert, MD Columbia University Medical Center Cincinnati, Ohio New York, New York Tufts University School of Medicine Azra Raza, MD Zartash Gul, MD Tufts Medical Center Boston, Massachusetts Memorial Sloan-Kettering Cancer Center The Ohio State Comprehensive New York, New York Kellie Sprague, MD Cancer Center, James Cancer Hospital Virginia M. Klimek, MD and Solove Research Institute MICHIGAN Northwell Health Cancer Institute Columbus, Ohio Barbara Ann Karmanos Cancer Institute at Monter Cancer Center James S. Blachly, MD/Alison R. Walker, MD Wayne State University Lake Success, New York Detroit, Michigan Steven L. Allen, MD PENNSYLVANIA Charles A. Schiffer, MD Laura & Isaac Perlmutter Cancer Center Allegheny Health Network Cancer Institute at NYU Langone Health Western Pennsylvania Hospital William Beaumont Hospital Cancer Center Pittsburgh, Pennsylvania Royal Oak, Michigan New York, New York Ishmael Jaiyesimi, DO Maher Abdul Hay, MD Salman Fazal, MD Icahn School of Medicine at Mount Sinai Fox Chase Cancer Center MINNESOTA New York, New York Philadelphia, Pennsylvania Mayo Clinic Lewis R. Silverman, MD Philip Pancari, MD Rochester, Minnesota New York Medical College/Westchester Mark R. Litzow, MD University of Pennsylvania Cancer Center Medical Center, Zalmen A. Arlin Cancer Center Philadelphia, Pennsylvania University of Minnesota Valhalla, New York Karen Seiter, MD Selina Luger, MD Medical Center, Fairview University of Minnesota Medical School Roswell Park Cancer Center UPMC Cancer Center Minneapolis, Minnesota Buffalo, New York Pittsburgh, Pennsylvania Erica D. Warlick, MD Elizabeth Griffiths, MD/James E. Thompson, MD Anastasios Raptis, MD/James M. Rossetti, DO

21 TENNESSEE OUTSIDE THE UNITED STATES Universidade Federal de São Paulo Vanderbilt University Medical Center São Paulo, Brazil Nashville, Tennessee ARGENTINA Maria de Lourdes Chauffaille, MD, PhD Sanjay Mohan, MD/Michael R. Savona, MD Sanatorio Sagrado del Corazón Buenos Aires, Argentina CANADA TEXAS Marcelo Iastrebner, MD Princess Margaret Hospital Texas Oncology – San Antonio Toronto, Ontario, Canada San Antonio, Texas ARMENIA Karen Yee, MD Roger M. Lyons, MD, FACP Muratsan University Hospital Odette Cancer Centre Texas Oncology, Midtown Complex of Yerevan State Medical University Sunnybrook Health Sciences Center Austin, Texas Yerevan, Armenia Toronto, Ontario, Canada Richard Helmer, III, MD Gevorg Tamamyan, MD Rena Buckstein, MD, FRCPC Richard A. Wells, MD University of Texas AUSTRALIA MD Anderson Cancer Center Cabrini Haematology & Oncology Centre St. Paul’s Hospital Houston, Texas Melbourne, Australia Vancouver, British Columbia, Canada Guillermo Garcia-Manero, MD Melita Kenealy, MD Heather Leitch, MD, PhD Hagop Kantarjian, MD Monash Health Monash University University of Toronto University of Texas Clayton, Victoria, Australia Hospital for Sick Children Southwestern Medical Center Jake Shortt, BMedSc, MBChB FRACP FRCPA PhD Toronto, Ontario, Canada Dallas, Texas Yigal Dror, MD Robert H. Collins, Jr., MD, FACP Peter MacCallum Cancer Institute University of Melbourne CHINA UTAH East Melbourne, Australia University of Utah Huntsman Cancer Institute John F. Seymour, MD Guangdong General Hospital & Salt Lake City, Utah Guangdong Academy of Medical Sciences Paul J. Shami, MD The Royal Melbourne Hospital Guangzhou, China Parkville, Victoria, Australia Xin Du, MD, PhD VIRGINIA David Ritchie, MD Institute of Hematology University of Virginia Charlottesville, Virginia AUSTRIA and Blood Diseases Hospital Michael Keng, MD Hanusch Hospital Chinese Academy of Medical Sciences Medical University of Vienna Tianjin, China WASHINGTON Vienna, Austria Zhijian Xiao, MD Michael Pfeilstöcker, MD Fred Hutchinson Cancer Research Center The First Affiliated Hospital of Soochow University of Washington Medical University of Vienna University, Jiangsu Institute of Hematology Seattle Cancer Care Alliance Vienna, Austria Jiangsu Province, China Seattle, Washington Peter Valent, MD Suning Chen, MD, PhD Joachim Deeg, MD/Elihu Estey, MD University Hospital of Innsbruck The First Affiliated Hospital Innsbruck, Austria WASHINGTON, DC of Zhejiang University Reinhard Stauder, MD Georgetown University Hospital Zhejiang Province, China Lombardi Comprehensive Cancer Center Hongyan Tong, MD, PhD Washington, D.C. BELGIUM Catherine Broome, MD AZ Sint-Jan AV The Sixth Hospital Affliated to Brugge, Belgium Shanghai Jiaotong University George Washington University Dominik Selleslag, MD Shanghai, China VA Medical Center Washington, D.C. University Hospital Leuven Xiao Li, MD, PhD Charles S. Hesdorffer, MD Leuven, Belgium Marielle Beckers, MD, PhD CROATIA Michel Delforge, MD, PhD Clinical Hospital Merkur WISCONSIN Zagreb, Croatia American Family Children’s Hospital Inga Mandac Ragulj, MD University of Wisconsin Health BRAZIL Madison, Wisconsin AC Camargo Hospital–Cancer Center Inga Hofmann, MD São Paulo, Brazil CZECH REPUBLIC Luiz Fernando Lopes, MD, PhD Institute of Hematology & Blood Transfusion Medical College of Wisconsin Prague, Czech Republic Bone Marrow Transplant Program Hospital das clínicas da Faculdade de Jaroslav Cermák, MD, PhD Milwaukee, Wisconsin Medicina da Universidade de São Paulo Parameswaran Hari, MD São Paulo, Brazil DENMARK Elvira D. Rodrigues Pereira Velloso, MD, PhD University of Wisconsin Odense University Hospital The University of Southern Denmark Madison Medical School Universidade Federal de Ceará Madison, Wisconsin Ceará, Brazil Odense, Denmark Mark B. Juckett, MD Silvia Maria M. Magalhães, MD, PhD Klas Raaschou-Jensen, MD/Claus Marcher, MD

22 Rigshospitalet National University Hospital Heinrich-Heine Universität Düsseldorf University General Hospital Attikon Copenhagen, Denmark University Hospital Athens, Greece Kirsten Grønbaek, MD/Lars Kjeldsen, MD, PhD Düsseldorf, Germany Vassiliki Pappa, MD Ulrich Germing, MD FRANCE HUNGARY Johannes Gutenberg University Centre Henri Becquerel Semmelweis University School of Medicine Medical Center Mainz Budapest, Hungary Rouen University School of Medicine Mainz, Germany Rouen, France Judit Várkonyi, MD, PhD Markus Radsak, MD, PhD Aspasia Stamatoullas, MD Johann Wolfgang Goethe Universität INDIA Centre Hospitalier Universitaire (CHU) Frankfurt Main, Germany Tata Medical Centre de Angers Service des Maladies du Sang Gesine Bug, MD Kolkata, India Angers, France Col (Dr.) Deepak Kumar Mishra, MD Norbert Ifrah, MD Klinikum Rechts der Isar Technical University of Munich Tata Memorial Hospital Centre Hospitalier Universitaire Munich, Germany Mumbai, India (CHU) de Grenoble Katharina Götze, MD Manju Sengar, MD Grenoble, France MLL Münchner Leukämielabor Jean-Yves Cahn, MD Munich, Germany IRELAND Centre Hospitalier Universitaire Torsten Haferlach, MD/Wolfgang Kern, MD Adelaide and Meath Hospital Dublin, Ireland (CHU) de Limoges Hôpital Dupuytren Rems-Murr-Klinik Winnenden Helen Enright, MD Limoges, France Winnenden, Germany Dominique Bordessoule, MD Stefani Parmentier, MD ISRAEL Centre Hospitalier Universitaire St. Johannes Hospital Tel-Aviv Sourasky Medical Center (CHU) de Nancy Heinrich-Heine Universität Tel-Aviv, Israel Nancy, France Duisburg, Germany Moshe Mittelman, MD Agnés Guerci-Bresler, MD, PhD Carlo Aul, MD,PhD/Aristotle Giagounidis, MD,PhD Chaim Sheba Medical Center Centre Hospitalier Universitaire University of Heidelberg Medical Center Tel Hashomer, Israel (CHU) de Tours – Bretonneau St. Lukas Klinik Solingen Drorit Grizim Merkel, MD Tours, France Solingen, Germany Emmanuel Gyan, MD, PhD Ulrich Mahlknecht, MD, PhD ITALY Cancer Center – IRCCS Humanitas Hôpital Avicenne/University Paris XIII Albert-Ludwigs-Universität Freiburg Bobigny, France Freiburg, Germany Research Hospital Milan, Italy Charikleia Kelaidi, MD Michael Lübbert, MD, PhD Matteo G. Della Porta, MD Hôpital Cochin/University Paris V Universität Hamburg Paris, France Hamburg, Germany Centro di Riferimento Francois Dreyfus, MD Nicolaus Kröger, MD, PhD Oncologico di Basilicata (CROB) Rionero in Vulture (PZ), Italy Hôpital Saint Louis/University Paris VII Universitätsklinikum Carl Gustav Carus Pellegrino Musto, MD Paris, France Dresden, Germany Pierre Fenaux, MD, PhD Katja Sockel, MD Istituto di Ematologia Christine Chomienne, MD, PhD Universita’ Cattolica Sacro Cuore University Children’s Hospital Rome, Italy Hôpital Saint-Vincent de Paul (Lille) Freiburg, Germany Giuseppe Leone, MD Lille, France Charlotte Niemeyer, MD Christian Rose, MD Policlinico Tor Vergata University of Cologne Rome, Italy Institut Paoli-Calmettes Cologne, Germany Sergio Amadori, MD/Maria Teresa Voso, MD Marseille, France Karl-Anton Kreuzer, MD Norbert Vey, MD S. Eugenio Hospital Tor Vergata University University Hospital Leipzig Rome, Italy Service des Maladies du Sang Leipzig, Germany Paolo de Fabritiis, MD/Pasquale Niscola, MD Hôpital Claude Huriez Uwe Platzbecker, MD Lille, France University of Florence Azienda OSP Careggi Florence, Italy Bruno Quesnel, MD University Hospital Mannheim Mannheim, Germany Valeria Santini, MD Wolf-Karsten Hofmann, MD GERMANY University of Pavia School of Medicine Georg-August-Universität Göttingen GREECE Fondazione IRCCS Policlinico San Matteo Göttingen, Germany Pavia, Italy Patras University Hospital Detlef Haase, MD, PhD Patras, Greece Mario Cazzola, MD Argiris Symeonidis, MD Hannover Medical School JAPAN Medizinische Hochschule Hannover University of Athens Laikon Hospital Kyoto University Hospital Hannover, Germany Athens, Greece Kyoto, Japan Arnold Ganser, MD Nora Viniou, MD Akifumi Takaori, MD

23 Metropolitan Research and Treatment Center SOUTH KOREA TUNISIA for Blood Disorders (MRTC Japan) Catholic Blood and Marrow Hospital Aziza Othmana Tokyo, Japan Transplantation Center Tunis, Tunisia Kiyoyuki Ogata, MD, FACP The Catholic University of Korea Balkis Meddeb, MD Nagasaki University Hospital School of Seoul, Korea Medicine, Atomic Bomb Disease Institute Yoo-Jin Kim, MD TURKEY Nagasaki City, Japan Ankara University Yasushi Miyazaki, MD Seoul National University Hospital School of Medicine Hospital Seoul National University Ankara, Turkey Saitama Medical University College of Medicine Osman Ilhan, MD International Medical Center Seoul, Korea Hidaka, Saitama, Japan Dong Soon Lee, MD, PhD Tomoya Maeda, MD, PhD UKRAINE Yonsei Cancer Centre, Severance Hospital Research Center for Radiation Medicine Tokyo Medical College Kiev, Ukraine Yonsei University College of Medicine Tokyo, Japan Dimitry Bazyka, MD Kazuma Ohyashiki, MD, PhD Seoul, Korea June-Won Cheong, MD, PhD UNITED KINGDOM MEXICO Aberdeen Royal Infirmary Instituto Nacional de Ciencias Medicas SPAIN Aberdeen University School of Medicine y Nutrición Salvador Zubiran Hospital Universitario de Salamanca Salamanca, Spain Foresterhill, Aberdeen, Scotland American-British-Cowdray Cancer Center Dominic Culligan, MD Mexico City, Mexico Maria Diez-Campelo, MD, PhD Alvaro Aguayo, MD Hospital Universitario La Fe Cambridge University Hospitals Valencia, Spain Cambridge, United Kingdom THE NETHERLANDS Guillermo F. Sanz, MD, PhD Alan J. Warren, MD, PhD Radboud University Christie NHS Foundation Trust Nijmegen Medical Center Vall d’Hebron Institute of Oncology Manchester, United Kingdom Nijmegen, The Netherlands Universitary Hospital Vall d´Hebron Saskia M.C. Langemeijer, MD Barcelona, Spain Mike Dennis, MD/Dan Wiseman, MD Vrije Universiteit Medical Center David Valcárcel, MD, PhD King’s College London & Amsterdam, The Netherlands King’s College Hospital Arjan A. van de Loosdrecht, MD, PhD SWEDEN London, United Kingdom Karolinska Institute at Ghulam J. Mufti, DM, FRCP, FRCPath POLAND Karolinska University Hospital Huddinge Queen Elizabeth Hospital Jagiellonian University Collegium Medicum Stockholm, Sweden Kraków, Poland Eva Hellström-Lindberg, MD, PhD University Hospital Birmingham NHS Trust Birmingham, United Kingdom Aleksander Skotnicki, MD, PhD Manoj Raghavan, MD Medical University of Warsaw SWITZERLAND Warsaw, Poland Basel University Hospital Radcliffe Hospitals & University of Oxford Krzysztof Madry, MD Basel, Switzerland Oxford, United Kingdom Jakob R. Passweg, MD, MS Paresh Vyas, MD PORTUGAL Bern University Hospital Royal Bournemouth Hospital Hospital de Santa Maria Bournemouth, United Kingdom Lisbon, Portugal and University of Bern Bern, Switzerland Sally Killick, MD Joao F. Lacerda, MD Nicolas Bonadies, MD St. James’s University Hospital SAUDI ARABIA University Hospital Zurich St. James’s Institute of Oncology Leeds, United Kingdom King Faisal Specialist Hospital & Research Centre Zurich, Switzerland Riyadh, Saudi Arabia Markus G. Manz, MD/Stefan Balabanov, MD David T. Bowen, MD Amr Hanbali, MD University Hospital Southampton King Khaled University Hospital TAIWAN (NHS Foundation Trust) King Saud University Chang Gung Memorial Hospital Southampton, Hampshire, UK Riyadh, Saudi Arabia Chang Gung University Christopher Dalley, MD Ak Almomen, MD Taoyuan, Taiwan Srinivasan Narayanan, MD Lee-Yung Shih, MD SINGAPORE University Hospital of Wales Cardiff, Wales Singapore General Hospital National Taiwan University Hospital Aloysius Ho, MD Taipei, Taiwan Jonathan Kell, MD Hwei-Fang Tien, MD, PhD SOUTH AFRICA VIETNAM University of Cape Town THAILAND National Institute of Hematology Groote Schuur Hospital King Chulalongkorn Memorial Hospital and Blood Transfusion Cape Town, South Africa Pathumwan, Bangkok, Thailand Hanoi, Vietnam Nicolas Novitzky, MD, PhD Tanin Intragumtornchai, MD Khanh Quoc Bach, MD, PhD

24 WE NEED YOU

HOW YOU CAN HELP

JOIN THE FOUNDATION AS A MEMBER* • You are part of the solution to change MDS outcomes. Your membership fee helps support global physician and patient educational initiatives, and helps to empower patients with courage and hope. • Updates on the status of our Global Centers of Excellence and their live patient and family forum events that allow for more rapid dissemination of new research and treatment developments. • Information on the latest clinical trials to potentially share or participate in. • Access to MDS awareness materials to share with family and friends. • Opportunities to participate in or host support group events with your friends and community. • Receive two printed issues of The MDS News, which includes the latest on MDS research as well as inspiring patient and caregiver stories.

DONATE TO SUPPORT OUR MISSION* • All donations are tax-deductible. Thank you in advance for your support!

AMAZON SMILE • When you shop with Amazon Smile, Amazon will donate 0.5% of the price of an eligible purchase to the MDS Foundation. All you have to do is select Myelodysplastic Syndromes Foundation as your charity of choice.

VOLUNTEER* • Volunteers are vital to our mission.

*PLEASE VISIT https://www.mds-foundation.org to discover how can you join, donate and volunteer

25 JOIN2014 THE RARE MDS DISEASE FOUNDATION DAY

THINKING OF JOINING THE MDS FOUNDATION AS A PROFESSIONAL MEMBER OR CHANGING THE FUTURE OF MDS MEMBER? To join the MDS Foundation and help us fulfill our mission of moving closer to a cure for MDS, please visit our website at http://www.mds-foundation.org/professional-annual-membership-application. CURRENT PROFESSIONAL MEMBERS UNITED STATES: Aref Al-Kali, MD • Steven Allen, MD • Kimo Bachiashvili, MD • Maria Baer, MD • Asad Bashey, MD, PhD • Rafael Bejar, MD, PhD • John Bennett, MD • Emmanuel Besa, MD • Kelly Bolton, MD, PhD • Andrew M. Brunner, MD • Victor Chang, MD, FACP • Alden Chesney, MD • Christopher Cogle, MD • Robert Collins, Jr., MD, FACP • Seth J. Corey, MD • Larry Cripe, MD • Peter T. Curtin, MD • Magdalena Czader, MD, PhD • Carlos de Castro, MD • Matthew De Silva • H. Joachim Deeg, MD • Amy E. DeZern, MD, MHS • John DiPersio, MD, PhD • Erika Eksioglu PhD, MS • Salman Fazal, MD • Maria Figueroa, MD • James Foran MD, FRCPC • Stephen Forman, MD • Matthew Foster, MD • Steven Fruchtman, MD • Alejandro Garcia-Hernandez, MD • Guillermo Garcia-Manero, MD • Stuart Goldberg, MD • Timothy Graubert, MD • Peter Greenberg, MD • Elizabeth Griffiths, MD • Zartash Gul, MD • Gregory Hale, MD • Michel Hoessly, MD • Aaron Hoskins, PhD • Ishmael Jaiyesimi, MD • Brian A. Jonas, MD, PhD • Mark Juckett, MD • Hagop Kantarjian, MD • Michael Keng, MD • Jeffery Klco, MD • Virginia M. Klimek, MD • Rami Komrokji, MD • Amelia Langston, MD • Richard Larson, MD • Jane Liesveld, MD • Mark Litzow, MD • Selina Luger, MD • Roger Lyons, MD, FACP • Philip McCarthy, MD • Stephen Medlin, DO • Kenneth Meehan, MD • Clelie Melancon, MD • Raul R. Mena, MD • Melissa Mendez • Sanjay Mohan, MD • Lynn Moscinski, MD • Stephen Nimer, MD • Casey O'Connell, MD • Margaret R. O'Donnell, MD • Daniel Pollyea, MD, MS • Nagesh Rao, PhD, FACMG • Anastasios Raptis, MD • Azra Raza, MD • Brandi Reeves, MD • James M. Rossetti, MD • David Sallman, MD • Srinivasa Sanikommu, MD, FACP • Marianne Santaguida, PhD • Michael Savona, MD, FACP • Hamid Sayar, MD • Dale Schaar, MD, PhD • Gary Schiller, MD • Richard K. Shadduck, MD • Paul Shami, MD • Jamile Shammo,MD, FASCP, FACP • Akiko Shimamura, MD, PhD • Barry Skikne, MD, FACP, FCP(SA) • Kellie Sprague, MD • Lisa Sproat, MD, MSW • David Steensma, MD • Sandra Swantek, MD • Sachdev Thomas, MD • James Thompson, MD • Swapna Thota, MD • Zuzana Tothova, MD, PhD • Thu Le Trinh, MD • Amit Verma, MD • Alison Walker MD, MPH • Erica Warlick, MD • Cecilia Yi, MD • Amer Zeidan, MD OUTSIDE OF THE UNITED STATES: Sergio Amadori, MD • Stefan Balabanov, MD • Indira Barbosa, BMA • Mariëlle Beckers, MD, PhD • Ann-Charlotte Björklund • Nicolas Bonadies, MD • Gesine Bug, MD • Jaroslav Cermak, MD, PhD • Suning Chen, MD, PhD • June-Won Cheong, MD • Michel Delforge, MD, PhD • Matteo Della Porta, MD • Maria Diez-Campelo, MD, PhD • Kalman Filanovsky, MD • Arnold Ganser, MD • Ulrich Germing, MD • Katharina Gotze, MD, PhD • Kirsten Grønbæk, Professor, MD • Emmanuel Gyan, MD, PhD • Detlef Haase, MD, PhD • Torsten Haferlach, MD • Stefa Heinrichs, PhD • Eva Hellstrom-Lindberg, MD, PhD • Irachmiel Huber, MD • Monika Jansson • Jonathan Kell, MD • Melita Kenealy, MD • Wolfgang Kern, MD, Professor • Anjum Khan, MD • Sally Killick, MD • Lars Kjeldsen, MD, PhD • Nicolaus Kroeger, MD, PhD • Saskia Langemeijer, MD, PhD • Heather Leitch, MD, PhD • Xiao Li, MD • Krzysztof Madry, MD, PhD • Tomoya Maeda, MD, PhD • Ulrich Mahlknecht, MD, PhD • Inga Mandac Rogulj, MD • Markus Manz, MD • Claus Marcher, MD • Yasushi Miyazaki, MD • Teresa Mortera Blanco, PhD • Charlotte Niemeyer, MD • Kiyoyuki Ogata, MD, PhD, FACP • Stefani Parmentier, MD • Michael Pfeilstöcker, MD • Uwe Platzbecker, MD • Klas Raaschou-Jensen, MD • Markus Radsak, MD, PhD • Fernando Ramos, MD, PhD, MPH • Kevin Rouault-Pierre, PhD • Alicia Rovo, MD • Aleksandar Savic, Professor, MD • Mary Lynn Savoie, MD • John Seymour, MD • Lee-Yung Shih, MD • Jake Shortt, MD • Katja Sockel, MD • Reinhard Stauder, MD • Argiris Symeonidis, MD • Akifumi Takaori-Kondo, MD, PhD • Hwei-Fang Tien, MD, PhD • David Valcárcel, MD, PhD • Norbert Vey, MD • Athina Nora Viniou, MD • Despoina Violidaki, MD • Sara von Bahr Grebäck, PhD • Maria Teresa Voso, MD • Alan Warren, MD, PhD • Zhijian Xiao, MD • Yumi (Yamamoto) Ogata, BA • Karen Yee, MD • Yataro Yoshida, MD

CURRENT CHANGING THE FUTURE OF MDS MEMBERS: Camille Abboud, MD • Andrew Adams • Aref Al-Kali, MD • Kimo Bachiashvili, MD • Barbara Bartlett • Mariëlle Beckers, MD, PhD • George Benson • Robert Bills • David Carden • Victor Chang, MD, FACP • Cheryl Coleman • Renee Conrad • Laurence Cove and Ann Brody Cove • Magdalena Czader, MD, PhD • John Soper, PhD, DABCC • Mark and Martha De Noble • James and Josephine Diedrich • Sally Ferguson • Lewis Flock • Steven Fruchtman, MD • Roman Suarez Garcia • David Galli • Andrew Glasgow • Stuart L. Goldberg, MD • Janice Gottlieb • Lee Harris • Theron and Brooke Hatch • Robert J. Heiss • Michel Hoessly, MD • Michael Hollander • Lou and Kathy Jerge • Diane Jordan • Mark B. Juckett, MD • Jeffery Klco, MD • Marilee Korsinen • Marti Lawrence-Grant • Cathy Layton • Connie Lee Frederic and Kathleen Leverenz • James Lewin • G Malcolm Louden • Gene Lynes • Joe Maloney • David Mandell • Phyllis Mandell • Daniel McCormick • Robert McElveen • Julia McGuire • Milt Miller • Joseph O. Moore, MD • Yumi (Yamamoto) Ogata, BA • James Phillips • Katherine Radosh • Brandi Reeves, MD • Harvey P. Root • Lorne Ruby • Walt Smith • John Stasenko • Joseph Strothers • Richard Sturm • Sandra Swantek, MD • Sachdev Thomas, MD • Swapna Thota, MD • Theresa Tintor • Janet B. Warfield • Stephen Francis Weber • Michael Weiner • Leon Weiss • JoEllen White • Kenan White • Leonard Yool

26 2020 PATIENT FORUMS

SPREADING2014 RARE THE NEWSDISEASE WORLDWIDE DAY

MARK YOUR CALENDAR FOR THE LOCATION NEAREST YOU! PATIENT FORUMS 2020 INFORMATIVE FEBRUARY 1 Birmingham, AL FEBRUARY 22 Houston, TX MARCH 6 PLEASE NOTE THAT DURING THE COVID-19 OUTBREAK, Tel Aviv, Israel WE MAY BE OFFERING VIRTUAL EVENTS VIA WEBINAR. WE WILL CONTINUE TO ASSESS ANY JUNE 27 FURTHER DEVELOPMENTS AS THEY COME. Madison, WI JULY 25 Chicago, IL AUGUST 8 Palo Alto, CA REGISTER AUGUST 29 Denver, CO 2020 SEPTEMBER 12 New York, NY SEPTEMBER 26 Chapel Hill, NC DON'T MISS OUT ON THESE INFORMATIVE, FREE EVENTS OCTOBER 30 REGISTRATION IS REQUIRED Omaha, NE Register online at NOVEMBER 7 https://www.mds-foundation.org/patient-and-family-forums. Tampa, FL To register by phone or for any questions, call or email Janice Butchko at 1-800-637-0839 Ext. 212; [email protected]

LEARN MORE AT: www.mds-foundation.org/patient-and-family-forums Many patients and caregivers have never met another person diagnosed with MDS until they connected with them at one of our forums. If you’ve never attended one, you won’t want to miss this opportunity to meet others and to learn more about MDS, current treatments, and emerging therapies from leading experts. Not only will you find answers, support and hope for MDS but you will learn tips and strategies for patients and caregivers LIVING with MDS. PLEASE MAKE SURE TO REGULARLY CHECK OUR WEBSITE FOR MEETINGS TAKING PLACE IN A CITY NEAR YOU!

27 IN THE NEWS

PRESS RELEASES

U.S. FDA APPROVES overload, transfusion site reactions and stimulating agent (ESA) therapy or were ESA infections. In our current environment, we naïve and unlikely to respond due to REBLOZYL® (LUSPATERCEPT- are reminded of the significant burden endogenous serum erythropoietin ≥200 U/L, AAMT), THE FIRST AND ONLY frequent blood transfusions can have on and had no prior treatment with disease ERYTHROID MATURATION individuals and the healthcare system.” modifying agents. AGENT, TO TREAT ANEMIA “Today’s approval of Reblozyl is an In the trial, a significantly greater IN ADULTS WITH important milestone for a majority of patients proportion of patients receiving Reblozyl LOWER-RISK MDS with myelodysplastic syndromes who have achieved independence from RBC PRINCETON, NJ & CAMBRIDGE, MA, limited treatment options to address anemia transfusions for at least eight weeks during APRIL 3, 2020 — The FDA approval associated with their disease. It also the first 24 weeks of the trial compared with marks the second indication for Reblozyl demonstrates our continued commitment to those receiving placebo, meeting the 2 and the first new treatment option in over develop innovative products that improve the study’s primary endpoint. Additionally, a a decade for patients with MDS who lives of patients living with serious diseases,” significantly greater proportion of patients require red blood cell (RBC) transfusions said Diane McDowell, MD., vice president, receiving Reblozyl vs. placebo achieved at and have failed an erythropoiesis Hematology Global Medical Affairs, Bristol least 12 weeks of independence from stimulating agent. Myers Squibb. “We are looking forward to transfusions within the first 24 and 48 Reblozyl regulates late-stage RBC making Reblozyl immediately available for weeks of the study.2 maturation to relieve patients from the this patient population.” The majority of treatment-emergent burden of regular RBC transfusions. The FDA approval in MDS is based on adverse events (TEAEs) in the trial were Bristol Myers Squibb (NYSE: BMY) and results from the pivotal Phase 3 MEDALIST Grade 1–2. Grade 3 or 4 treatment- Acceleron Pharma Inc. (NASDAQ: XLRN) trial and marks the second indication for emergent adverse events were reported in today announced the U.S. Food and Drug Reblozyl, which received its first approval 42.5% of patients who received Reblozyl Administration (FDA) has approved Reblozyl® in November 2019 for the treatment of and 44.7% of patients who received (luspatercept-aamt), the first and only erythroid anemia in adults with beta thalassemia placebo. The most common (>10%) all- maturation agent (EMA), for the treatment who require regular RBC transfusions.1 grade adverse reactions included fatigue, of anemia failing an erythropoiesis stimulating “We’re excited that Reblozyl has been musculoskeletal pain, dizziness, diarrhea, agent and requiring 2 or more red blood cell approved to help even more patients in need dyspnea, nausea, hypersensitivity (RBC) units over 8 weeks in adult patients with of treatment options,” said Habib Dable, reactions, headache, and upper very low- to intermediate-risk myelodys-plastic President and Chief Executive Officer, respiratory tract infection.2 syndromes with ring sideroblasts (MDS-RS) Acceleron. “We are enormously grateful to Results from MEDALIST were published or with myelodysplastic/myeloproliferative the patients, families and caregivers who in the New England Journal of Medicine in neoplasm with ring sideroblasts and participated in and supported the Reblozyl January 2020. thrombocytosis (MDS/MPN-RS-T). Reblozyl clinical trials, and to the researchers at ABOUT REBLOZYL® is not indicated for use as a substitute for Acceleron and beyond who, more than a RBC transfusions in patients who require decade ago, began this important quest to Reblozyl, the first and only erythroid immediate correction of anemia.1 address patients’ chronic anemias.” maturation agent, promotes late-stage red “In clinical trials, Reblozyl has shown to blood cell maturation in animal models.1 ABOUT MEDALIST have significant benefit for the treatment of Bristol Myers Squibb and Acceleron are anemia in patients with myelodysplastic The approval of Reblozyl was based on jointly developing Reblozyl as part of a syndromes who have ring sideroblasts,” the findings of MEDALIST, a Phase 3, global collaboration. Reblozyl is currently said Guillermo Garcia-Manero, MD, randomized, double blind, placebo- approved in the U.S. for the treatment of: controlled, multi-center study evaluating the professor and chief of Section of • anemia in adult patients with beta Myelodysplastic Syndromes, Department of efficacy and safety of Reblozyl in patients thalassemia who require regular red Leukemia, University of Texas MD Anderson with IPSS-R-defined very low-, low- and blood cell transfusions, and intermediate-risk non-del(5q) myelodysplastic Cancer Center. “Anemia is a serious anemia failing an erythropoiesis syndromes (MDS) with ring sideroblasts. • consequence of MDS, requiring the stimulating agent and requiring 2 or All patients were red blood cell (RBC) majority of these patients to receive regular more red blood cell units over 8 weeks transfusion-dependent and were either red blood cell transfusions, which can lead in adult patients with very low- to refractory or intolerant to prior erythropoiesis- to additional complications, such as iron intermediate-risk myelodysplastic syn-

28 PRESS RELEASES

dromes with ring sideroblasts (MDS-RS) The program features: Astex Pharmaceuticals announces U.S. or with myelodysplastic/myeloproliferative • Immediate access for patients who Food and Drug Administration (FDA) neoplasm with ring sideroblasts and have lost their employment and health acceptance for review of an NDA for the thrombocytosis (MDS/MPN-RS-T). insurance; combination oral hypomethylating agent Reblozyl is not indicated for use as a • A simple, single point of entry; cedazuridine and decitabine (ASTX727 substitute for red blood cell transfusions in • Streamlined enrollment process; and or oral C-DEC), for the treatment of MDS patients who require immediate correction • Vouchers to assist with continuity of and CMML of anemia. care for several self-administered BMS • NDA is supported by data from the Indication medicines, for eligible patients phase 3 ASCERTAIN study of oral C- REBLOZYL is indicated for the treatment All Bristol Myers Squibb patient DEC in adults with intermediate- and of anemia in adult patients with beta support programs, as well as, additional high-risk myelodysplastic syndromes thalassemia who require regular red blood eligibility requirements, can be reached (MDS) including chronic myelomono- cell (RBC) transfusions by calling (800) 721-8909 or by visiting cytic leukemia (CMML) REBLOZYL is indicated for the treatment BMS.com. • FDA designated the application for of anemia failing an erythropoiesis “The COVID-19 pandemic has created Priority Review stimulating agent and requiring 2 or more unprecedented financial challenges for • Potential for oral C-DEC to become red blood cell units over 8 weeks in adult patients and families, adding considerable first approved orally administered patients with very low- to intermediate-risk new stress to the millions of Americans who hypomethylating agent for MDS and myelodysplastic syndromes with ring have lost their jobs and health insurance,” CMML in the U.S. sideroblasts (MDS-RS) or with myelodys- said Giovanni Caforio, MD, chairman and Astex Pharmaceuticals, Inc., a wholly plastic/myeloproliferative neoplasm with chief executive officer, Bristol Myers owned subsidiary of Otsuka Pharmaceutical Squibb. “As more patients face difficult ring sideroblasts and thrombocytosis Co. Ltd., based in Japan, today announced decisions in their daily lives, it is important (MDS/MPN-RS-T) that the U.S. FDA has accepted for Priority to continue their treatments.” REBLOZYL is not indicated for use as a Review its NDA for oral C-DEC (cedazuri- Bristol Myers Squibb’s Response to substitute for RBC transfusions in patients who dine and decitabine) as a treatment for COVID-19 require immediate correction of anemia. adults with previously untreated intermediate- Bristol Myers Squibb recognizes this is and high-risk MDS including CMML. The a challenging time for everyone. The NDA submission is based on data from the COVID-19: company will continue to take all IMMEDIATE RELIEF AVAILABLE ASCERTAIN phase 3 study which evaluated necessary actions to promote public health the 5-day decitabine exposure equivalence and carry out its mission of providing life- of oral C-DEC and IV decitabine. saving medicines to the patients who BRISTOL MYERS SQUIBB “We are very pleased that the FDA has depend on us. Please visit BMS.com to accepted our NDA for Priority Review,” EXPANDS PATIENT SUPPORT learn more about our actions to date. PROGRAMS TO HELP NEWLY said Dr Mohammad Azab, MD, president & chief medical officer of Astex UNINSURED PATIENTS IN ASTEX PHARMACEUTICALS Pharmaceuticals, Inc. “Subject to FDA THE U.S. ANNOUNCES U.S. FOOD review and regulatory approval, oral C- PRINCETON, NJ, APRIL 7, 2020 – DEC may offer a new option for patients AND DRUG ADMINISTRATION Bristol Myers Squibb (NYSE: BMY) with MDS and CMML that saves them the today announced an expansion of its (FDA) ACCEPTANCE FOR burden of 5-day IV infusions every month existing patient support programs to help REVIEW OF AN NDA FOR during their treatment period. We are eligible unemployed patients in the U.S. THE COMBINATION ORAL grateful to all the patients, investigators and who have lost their health insurance due to HYPOMETHYLATING AGENT other healthcare providers, and partner the COVID-19 pandemic. CEDAZURIDINE AND research and manufacturing organizations, The expanded program offers access to who contributed to the clinical development any branded Bristol Myers Squibb medicine DECITABINE (ASTX727 OR program of oral C-DEC.” for free, including some of its most widely ORAL C-DEC), FOR THE TREAT- The FDA grants Priority Review to prescribed products, as well as those MENT OF MDS AND CMML applications for drugs that, if approved, prescribed via telehealth services. PLEASANTON, CA, FEB 11, 2020 – would provide significant improvements in

29 PRESS RELEASES the safety and effectiveness of the treatment, designation for the treatment of MDS and REFERENCES diagnosis or prevention of serious conditions. CMML from the U.S. FDA. 01. Ferraris D, Duvall B, Delahanty G, Mistry B, The Priority Review designation means The concept of using cedazuridine to Alt, J, Rojas C, et al. Design, synthesis, and FDA’s goal is to take action on an NDA block the action of cytidine deaminase is pharmacological evaluation of fluorinated application within six months (compared to tetrahydrouridine derivatives as inhibitors of also being evaluated in a low dose cytidine deaminase. J Med Chem. 2014; the ten months under standard review). formulation of cedazuridine and 57:2582–2588. Oral C-DEC is an investigational decitabine for the treatment of lower risk 02. Oganesian A, Redkar S, Taverna P, Choy G, compound and is not currently approved in MDS (see https://www.clinicaltrials.gov Joshi-Hangal R, Azab M. Preclinical data in any country. NCT03502668). cynomolgus (cyn) monkeys of ASTX727, a novel oral hypomethylating agent (HMA) Astex’s parent company, Otsuka composed of low-dose oral decitabine ABOUT THE PHASE 3 ASCERTAIN STUDY Pharmaceutical Co., Ltd., and Taiho combined with a novel cytidine deaminase Pharmaceutical Co., Ltd. previously The study was designed as a randomized inhibitor (CDAi) E7727 [ASH Abstract]. announced that, subject to regulatory crossover study comparing oral C-DEC Blood. 2013; 122(21): Abstract 2526. approvals, commercialization of oral C- (cedazuridine 100 mg and decitabine 35 03. Savona MR, Odenike O, Amrein PC, Steensma DP, DeZern AE, Michaelis LC, et al. DEC in the U.S. and Canada will be mg fixed-dose combination tablet given once An oral fixed-dose combination of decitabine conducted by Taiho Oncology, Inc. and daily for 5 days on a 28-day cycle) to IV and cedazuridine in myelodysplastic Taiho Pharma Canada, Inc. respectively. decitabine (20 mg/m2 administered as a syndromes: a multicentre, open-label, dose- Astex, Otsuka and Taiho are all members daily, 1-hour IV infusion for 5 days on a 28- escalation, phase 1 study. Lancet Haematol [Internet]. 2019;6(4): e194-e203. of the Otsuka group of companies. day cycle) in the first 2 cycles with patients 04. Garcia-Manero G, McCloskey J, Griffiths continuing to receive oral C-DEC from Cycle ABOUT C-DEC (CEDAZURIDINE EA, et al. Pharmacokinetic exposure 3 onwards. The data from the ASCERTAIN 100 MG AND DECITABINE 35 MG) equivalence and preliminary efficacy and study was presented at the American Society safety from a randomized cross over Phase 3 FIXED-DOSE COMBINATION of Hematology (ASH) Meeting in Orlando, study (ASCERTAIN study) of an oral C-DEC is a novel, orally administered hypomethylating agent ASTX727 (cedazuri- Florida in December 2019 by Dr Guillermo dine/decitabine) compared to IV decitabine. fixed dose combination of cedazuridine, an Garcia-Manero, MD, professor and chief of Blood. 2019;134 (Supplement_1). 1 inhibitor of cytidine deaminase, with the anti- section of myelodysplastic syndromes, 05. Garcia-Manero G. Myelodysplastic syn- cancer DNA hypomethylating agent, Department of Leukemia at The University of dromes: 2015 update on diagnosis, risk- 2 decitabine. By inhibiting cytidine deaminase Texas MD Anderson Cancer Center, on stratification and management. Am J Hematol. 2015;90(9) 831–841. in the gut and the liver, C-DEC is designed to behalf of the study investigators.4 The data allow for oral delivery of the approved DNA 06. Ma X, Does M, Raza A, Mayne ST. demonstrated that the ASCERTAIN study met Myelodysplastic syndromes: Incidence and hypomethylating agent, decitabine, at the primary endpoint of total 5-Day survival in the United States. Cancer. exposures which emulate exposures achieved decitabine Area-Under-The-Curve (AUC) 2007;109(8):1536–1542. with the approved intravenous form of equivalence of oral C-DEC and IV 07. Cogle C. Incidence and burden of the 3 myelodysplastic syndromes. Curr Hematol decitabine administered over 5 days. decitabine. Safety findings from the study Malig Rep. 2015;10(3):272–281. C-DEC has been evaluated in a phase were consistent with those anticipated with IV 08. Shukron O, Vainstein V, Kündgen A, 1/2 pharmacokinetics-guided dose decitabine, with no significant differences in Germing U, Agur Z. Analyzing trans- escalation and dose confirmation study in the incidence of most common adverse formation of myelodysplastic syndrome to patients with MDS and CMML (see https: events between oral C-DEC and IV secondary acute myeloid leukemia using a large patient database. Am J Hematol. //www.clinicaltrials.gov NCT02103478) decitabine in the first 2 randomized cycles. 2012;87:853–860. and a pivotal phase 3 study (ASCERTAIN) The most common adverse events of any 09. What are the key statistics about chronic (see https://www.clinicaltrials.gov NCT- grade >20% regardless of causality in myelomonocytic leukemia? American Cancer 03306264) conducted at investigator sites patients in the first 2 randomized cycles Society Web site. https://www. cancer.org/ in the US and Canada and designed to who received oral C-DEC were thrombo- cancer/chronic-myelomonocytic-leukemia/ about/key-statistics.html. Accessed 1-27-20. confirm the results from the phase 1/2 cytopenia (43.8%), neutropenia (35.4%), 10. About chronic myelomonocytic leukemia study. The phase 3 study is now being anemia (36.9%), and fatigue (23.8%). The (CMML). Cancer Research UK Web site. extended to include patients with acute ASH presentation can be downloaded https://www.cancerresearchuk.org/about myeloid leukemia (AML) unsuitable to from the Astex website at https://astx.com -c a n c e r /o t h e r- c o n d i t i o n s /c h r o n i c - receive intensive induction chemotherapy. /media-center/presentations- inmyelomonocytic-leukaemia-cmml/about. In September 2019 Astex announced andpublications/ASTX727 ASCERTAIN Accessed 1-27-20. that C-DEC had received orphan drug Presentation - ASH - December 2019.

30 IN YOUR OWN WORDS

TESTIMONIALS

“Amazing! The website is full of “I have only recently been diagnosed with VALUABLE INFORMATION IN VARIOUS MDS, high risk at 5% (although I’m not quite “I am in awe of everything FORMS for all types of viewers. The sure what that means – yet). I AM VERY the MDS Foundation is doing. information package that was sent home is full PLEASED TO HAVE FOUND THIS SITE Bless you all for the work you of wonderful books that will help my mother and have been reading the message board. I do and the comfort you give.” learn more about MDS. Definitely exceeded am a 66 year old female. My care will be at Janice C. my expectations!!! Thank you so much. It’s nice Seattle Cancer Alliance. Thank you for making “The information they share to see an excellent foundation.” – Diane S. this informative site available!” – Cynthia H. is invaluable and I will call “Recently diagnosed with so much to “Thank you for this great information! I am Audrey Hassan whenever learn, especially about living with it. This a PV patient diagnosed in 2012. I appreciate I have a question — she is organization seems to OFFER KNOWLEDGE YOUR TIME AND DEDICATION IN fantastic at research and AND SUPPORT, which I for one, need. SUPPORT FOR ALL OF US with these always has answers for me! While I want to learn as much as I can about varied diagnoses.” – Mary G. I don’t feel so alone now. the disease, reading about the experiences of “I wish to inform you that I have well Thank you!” Jane B. others with it I find very comforting.” – Pat M. received the book Building Blocks of Hope by “I appreciate you speaking with me a few the post. Thank you very much. I have started minutes ago, your kind words and prompt the reading and am sure the INFORMATION email. I have already called Vanderbilt and IT CONTAINS WILL BE OF GREAT USE made an appointment for my father in a few TO UNDERSTAND MDS.” – Linda C. days. THANK YOU FOR YOUR WORK “The Postie delivered your generous IN HELPING MDS PATIENTS AND The Building Blocks of Hope Handbook parcel today to Perth containing bracelets provides strategies for patients and caregivers THEIR FAMILIES. God’s blessings!” – and books with so much information. In our living with MDS. This program is designed to give Jacqueline A. journey, YOU ARE THE ONLY PLACE patients and caregivers the in depth information “THANK YOU VERY MUCH for the THAT HAS GIVEN US TRUE that they are looking for and to allow them to take work you are doing on behalf of MDS INFORMATION. It is great to have a book an active part in their MDS journey. The BBoH is patients, their families, and the larger MDS that you can pick up and put down and so available in several languages. Call 1-800-MDS- community.” – Joey W. slowly digest the heavy subject.” – Kerry J. 0839 for your FREE copy today.

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MDS GLOSSARY Hearing the words Myelodysplastic Syndromes COMMONLY USED BONE MARROW FAILURE TERMS or MDS can be frightening. The diagnosis of MDS is often unexpected and filled with both immediate and long-term challenges. You probably have many questions. Have you accessed your complete set of tools to prepare, participate, and LIVE with MDS? Dealing with MDS can be very difficult, but it helps to have helpful resources that the myelodysplastic syndromes foundation, inc. are reliable and that you can trust.

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31 PATIENT STORIES

OUR PATIENT STORIES

MY JOURNEY TO A HAPLOIDENTICAL STEM CELL TRANSPLANT TOM HAYGOOD Hendersonville, Tennessee I have what?? Myelodysplastic Syndrome?? That’s how my journey began six years ago at age 62. It was the fall of 2013 when the common symptoms of MDS started. Fatigue and joint pain became a common occurrence in my everyday life. After a visit to my family doctor, blood tests were run and the results indicated some abnormalities. I was referred to a local hematologist who ordered additional blood tests along with a bone marrow biopsy and CT scan. With those results in After 19 months of shots, I had a port ahead. I began an intense round of 7-3 hand, I was diagnosed with MDS. Since implanted in March 2016 and began induction chemo to prepare my immune I’d never heard of the disease, the MDS receiving Vidaza infusions on the same 7 system for my upcoming SCT. The chemo Foundation and the Leukemia & Lymphoma day schedule. In October 2016, I walked was administered thru a PICC line. My wife Society were excellent resources to learn my daughter down the aisle at her kept a daily journal and began a website more about MDS. I also joined an MDS wedding in Denver! I changed to a 5 day for me on CaringBridge.org to keep our support group on Facebook. schedule of infusions in January 2017. family and friends updated. I had severe I live in Hendersonville, Tennessee, a In June 2017, after 32 rounds of mucositis from the chemo which made it suburb of Nashville, and was fortunate that Vidaza, my counts did not recover and a difficult to eat. I knew I would eventually I was able to receive all my treatment close bone marrow biopsy indicated 12% blasts. lose my hair, so I decided to shave my to home in Nashville. In January 2014, I I was referred to Dr. Carlos Bachier at the head one night. My wife was surprised the was referred to Tennessee Oncology at the Blood and Marrow Transplant Clinic at next morning to find a strange bald Sarah Cannon Cancer Center. I was Sarah Cannon Center for Blood Cancer at headed man in my room! On days when I evaluated with a series of tests and Centennial Medical Center. The Center is felt good enough, I walked laps around the determined to be a good candidate for a named after patient Sarah Cannon who was floor with a goal of 2 miles a day. My bone better known as Minnie Pearl of the Grand stem cell transplant. Since there was no marrow biopsy showed no evidence of Ole Opry! She offered the use of her given donor match from the international registry name and financial support to promote and my siblings were not suitable donors cancer research and patient education. due to health issues, the decision was My subtype of MDS was RAEB. I was made to have a haploidentical SCT. I have on “watch & wait” for 8 months. When my two daughters so they were both evaluated blood counts became lower and another as potential donors. My younger daughter bone marrow biopsy showed an increase Lisa, 32, was chosen as my donor since in blasts, I began treatment with Vidaza in she had never been pregnant, and my August 2014. I went 7 days a month, M-F older daughter had given birth to our three and M-Tu and received 3 subcutaneous awesome grandchildren. injections in my stomach. Other than I was admitted to the Immunosuppression irritation at the shot sites and fatigue, I had Unit at Sarah Cannon Cancer Center on minimal side effects, but I did retire in August 21, 2017, which was the date of September since my job required traveling the solar eclipse. That seemed appropriate and my immune system was very weak. since we anticipated some dark days Tom’s donor – his daughter, Lisa

32 OUR PATIENT STORIES disease, but I had to wait until my ANC count increased before I could be discharged. After 32 days in the hospital, I went home on Sept. 21 for 15 days. During that time, I had a Central Venous Catheter implanted for my upcoming SCT. On October 6, 2017, I was readmitted to the hospital for 5 days of chemo and one Total Body Irradiation treatment prior to my SCT. Lisa arrived from Denver and began her series of Neupogen injections to stimulate stem cell growth. She received two shots in her stomach for 5 days. She did not have any side effects from the shots and even ran in a 5K event one morning before coming to the hospital for her shots. She posted daily videos on Facebook to encourage others to register as donors on BetheMatch.org. On October 11, she had 580 million stem cells harvested in 7 hours of apheresis. Her only complaint was being bored during the procedure! I consider myself conservative, and it was the family joke that I would change after receiving her liberal stem cells! That didn’t happen. They were stem cells, not brain cells! On October 12, 2017, with my family surrounding me, I had my SCT which took about 30 minutes. Afterwards, I was given another 3 days of chemo and began all the medications for transplant patients. On the 18th day after my transplant, my bone marrow biopsy showed no blasts! I became an impatient patient waiting for my counts to increase. Finally, after 25 days in the hospital, I was discharged on October 30. Since I live within 30-45 minutes of the hospital, I was thrilled that I was allowed to go home instead of staying marrow biopsies. I have had some minor doctors and nurses, supportive family and in a facility near the hospital. It was a real skin and lung GVHD and neuropathy in my friends, and lots of answered prayers in the treat to be home for Halloween. My bone feet, but no other complications. past six years, and I am thankful for my marrow biopsy in November showed I celebrated my 2nd birthday last wonderful wife Gail who has been by my 100% donor cells and no blasts! I had lots October, and I enjoy playing golf with side in sickness and health for 47 years. I of follow-up appointments and stayed at friends 3-4 days a week! I am fortunate hope my journey will be encouraging to home most of that winter. Since that time, I that my haploidentical transplant was others diagnosed with MDS. have had regular follow-up visits and bone successful. I have been blessed with great

33 OUR PATIENT STORIES

My life at that time was very busy and LOOKING FORWARD blessed. I was a wife to a very special JANET B. WARFIELD, MSN man, mother to a beautiful 24 yr old Nashville, Tennessee daughter, Carly, and two precious King My journey with MDS began in March Charles Spaniels as well as a daughter to of 2014. My husband, Bill and I flew to two wonderful aging parents. I was CFO San Diego and then took a beautiful drive of a nonprofit called Mending Hearts, Inc. through the San Bernardino mountains to which is a residential treatment facility for Indian Wells. We had tickets to the Indian indigent women. I also had been a Wells professional tennis tournament. I was competitive tennis player for 20 years. especially excited because we were going I needed to learn more about this to get to see Rafa Nadal play. We arrived disease. I found the MDS Foundation on a Friday night exhausted from a long online. I requested information and they day of travel. I remember not feeling very biopsy I was diagnosed with primary sent me the Building Blocks of Hope, which well but went to dinner and then bed MDS. The fear that I experienced at that I still use as a resource today. I have hoping a good nights sleep was all I moment still resonates with me today. I attended three of their patient forums and needed. Bill was up bright and early the learned that I was young at age 58 to have participated in both Boston walks. The staff next morning. Although we had tickets to this rare form of blood cancer. My SF3B1 at the MDS Foundation is a group of see Rafa play that night, Bill went in search mutation with ringed sideroblasts put me in incredible women who have given me of tickets for the day sessions. I realized the low risk category of MDS which meant support and hope and I’m so very grateful after he left the hotel room that I literally that I was not at risk for developing to each of them. I’ve tried volunteering for could not get out of bed. I googled altitude leukemia. It also meant there were currently MDS research studies but so far I’ve not sickness as I was self diagnosing the no treatment options. So l left the qualified since I’ve not had any type of sudden onset of my fatigue. I slept all day oncologist that day in May of 2014 with a treatment. Instead of focusing on my and forced myself up and on the bus to the diagnosis of bone marrow cancer with a illness, I’ve been trying to focus on stadium to meet Bill for the night session to plan to return every 8 weeks for educating myself and connecting with see Rafa play. This was a bucket list moment bloodwork. As long as my numbers stayed others in the MDS community. I’m so for me and I wasn’t going to miss it. within a certain range, I would not qualify excited that Nashville will be hosting a Upon our return to Nashville, I had an for any of the available medical treatment MDS Awareness Walk in the fall of this appointment for my annual physical with protocols for MDS which was a good year! It’s so important that we bring my general practitioner. I told him about thing. The best advice he could give me awareness to this devastating disease. my episode of fatigue while on vacation. was to “just go live my life”. I also searched out alternative treatment He said everything checked out but he options in an attempt to improve my health. would be in touch with lab results from I began seeing a doctor of naturopathy in bloodwork. A week or so later I received a January 2015. I still see her twice a month letter that my blood was showing signs of for lymphatic massage, O2 therapy and anemia and I needed to return for more bemer mat sessions. She advices me on specific testing for vitamin deficiencies. A nutritional supplements that address my few days later, I received a call that suppressed immune system. She also changed my life. He said I didn’t have a encourages me to eat healthier. I have vitamin deficiency and that he was added Pilates and weight training to my referring me to a blood specialist for further exercise regimen. Are any of these things testing. I googled the specialist and my actually helping my MDS symptoms? I can heart almost stopped when I saw he was say that when I adhere to the regimen I sending me to an oncologist. have more energy. I have succumbed to My oncologist couldn’t have been nicer just one or two infections a year and my or more honest. After additional blood blood levels have remained about the work, a PET scan and a bone marrow same since 2014. I believe that being

34 OUR PATIENT STORIES proactive about my health has given me a played when first diagnosed. My visits to feeling of empowerment and it’s been a way the oncologist are still just every 8 weeks for for me to actively manage my disease. bloodwork and for that I’m most grateful. I have tried not to change my life My husband and daughter have been dramatically following my diagnosis. I my rock and they are the reason that each experience some fatigue most days and day is a blessing for me. They encourage shortness of breath when walking if the me to do all that I can but are so supportive terrain is not flat. I’ve found that I’m more when I need to slow down. MDS has had susceptible to infections. I’ve gradually a positive effect on how our family chooses learned what I need to do to manage these to live our daily lives. MDS was a huge symptoms. I did quit my job in the summer wake up call that life is short and each day of 2014. My parents’ health was is a gift not to be taken for granted. I keep beginning to fail and I wanted to be able my bucket list close by and am constantly to devote more of my time to them. My updating it. It keeps me hopeful and sweet mom passed in 2016. I miss her so focused on looking forward. I still much. My dad celebrated 93 years in experience the fear that comes with having October of last year. He has multiple health MDS, but that fear does not keep me from issues and is now living in a skilled nursing following my doctors orders to “go live my care facility but has the greatest attitude life”. I realize I’m one of the luckier ones and I treasure every minute I get to spend with a MDS diagnosis and that my with him. I am still playing competitive prognosis is better than most people in the tennis, although not at the same level I MDS community.

THANK YOU TO OUR INDUSTRY PARTNERS FOR THEIR SUPPORT

life’s ingredients

A SPECIAL THANK YOU for their very generous grant in support of MDS research

35 OUR PATIENT STORIES

CHASING THE CARROT... JILL WHITNEY Redding, California My journey with MDS (Myelodysplastic Syndromes) began in December 2007. After playing volleyball with my youngest daughter, I noticed that my forearms were badly bruised. This along with frequent headaches and fatigue prompted me to schedule an appointment for a physical. Little did I know our lives were about to change forever. We were getting ready to depart on a cruise to Cabo San Lucas, Mexico to I left my job as a registered dental assistant pass by on a giant calendar that showed celebrate my in-laws’ 50th anniversary, but and my counts stabilized. We were able to my daily blood counts and notes of my local hematologist wouldn’t allow me to put everything on hold for nearly a year inspiration from the nurses. I had hoped to go until a bone marrow biopsy was done. and a half. During this time, our first be discharged in time to spend the 4th of At first, he suspected a vitamin B-12 granddaughter arrived. July with my husband, but that day passed. deficiency. B-12 injections helped for a I was scheduled to begin the One good thing that came out of my late short time, but then my counts slowly conditioning for the transplant (cytoxin and release, was getting to meet Alex Smith, began to decline, especially my platelets. busulfan) on May 4, 2010, but due to quarterback for the San Francisco 49er’s After six long months and numerous respiratory symptoms, it was delayed. and several other team members when tests, I was finally referred to a hema- Having to wait an additional two weeks they paid a surprise visit to the BMT Unit. tologist at Stanford University Hospital in was disappointing, although I know it was On day +44, I was released to an Palo Alto, California. My husband and I for my own safety. I was admitted to the apartment we had rented nearby. At first, were told that I had MDS and a bone bone marrow transplant unit at Stanford on my husband took me to the infusion marrow transplant was the only cure. It May 17th and on May 25th I received the treatment area daily for blood draws and was a lot for us to absorb. We somehow life-saving stem cells from a 47-year old to receive needed transfusions. When he managed to hold it together through the male, German donor. I had a few setbacks returned to work, I was moved to my appointment, but as soon as we got to our that kept me in isolation longer than parents' home, about 30 minutes from car, we held each other and cried. I was expected. I spent four days in the ICU due Stanford. Then, I came down with CMV only 47. I couldn’t help but wonder if I to an E. Coli blood infection and then virus and had to remain close to Stanford would ever get to see our youngest contracted BK virus. I watched the days for an additional 6 weeks. I finally returned daughter graduate from high school or to my home in Redding at the end of even hold our first grandchild. I couldn’t September 2010. bear the thought of leaving my family. Eight months following the transplant, At the time, I was considered we were told that I had relapsed and a intermediate to high risk and my only second transplant wasn’t an option due to sibling was my half-brother, Jim, so a congestive heart failure. I was given a search began through the National prognosis of a few weeks to possibly a few Marrow Donor Program. I continued years, if I began treatment. I had not even working until we received word that four recovered from the transplant and was possible donor matches were found. Our now facing chemotherapy. We were youngest daughter was 14 and Stanford devastated. Desperate for help, my was four hours away from our home in husband and I attended an MDS Redding, California. We had a lot of Foundation conference in San Francisco, preparation to do before the transplant, so where Jason Gotlib, MD was a guest

36 OUR PATIENT STORIES speaker. My husband approached him also would not be here today without my after the event and asked if he would amazing family. Their love and accept me as a patient. I started receiving encouragement is what has kept me Vidaza (azacitadine) via port-a-cath in pushing forward. My husband, Roger, has February 2011, but my counts had a hard been my rock. I can’t count how many time recovering. For the first few months, I times he has driven me back and forth to was so sick that I needed help getting out Stanford or how many hours he has spent of bed. I was nauseated and had no sitting with me in doctor’s offices. He appetite. My family begged me to eat. At cooked, cleaned and took care of our times, I wanted to give up. youngest daughter and me. I know it I gave myself insulin and Neupogen wasn’t an easy job. My parents, Rick and injections and had to take numerous Lynne, and our eldest daughter, Amber, medications. For 18 months, I required were my caregivers when my husband was frequent transfusions until a bad reaction working and daughters, Candace and caused me to break out in huge welts all Kaylynn, helped in any way they could. over my body. From then on, the platelets searched for a way to give back and keep We also had the support of extended had to be HLA matched and packed. my mind off my illness. I volunteered in the family and friends. Luckily, things started turning around. Our Cancer Resource Center at our local I’m not done living yet. I have too much second granddaughter arrived in February hospital for a while and then I came up to look forward to. My husband and I both 2012. I pushed myself to get better so that I with an idea where I could work from turn 60 this year and in 2021 we will could be present at our youngest daughter's home. I started Signs of Hope and I have celebrate our 40th anniversary. I now have high school graduation and our middle now created over a hundred inspirational five beautiful grandchildren that keep me daughter's wedding a few months later. My signs to help others going through a on my toes and I want to be around to family kept dangling these carrots out in difficult time. Some I have donated to our watch them grow up. I have to keep front of me so that I would keep fighting. local hospital and to the oncology center chasing those carrots. where I receive treatment. I also started an MDS support group in my community with the assistance of the MDS Foundation. I am forever grateful for the incredible gift of life from my donor, Michael, and for the care I have received from the outstanding doctors, nurses and support staff at Mercy Medical Center and Stanford, including Dr. Gotlib and transplant specialist, Dr. Wen- Kai Weng. I I recently completed my 72nd cycle of Vidaza (azacitadine) and it has now been nine years since my relapse. On May 25, 2020, I will CELLebrate the tenth anniversary of my stem cell transplant (re- birthday). I tolerate chemotherapy pretty well now and take medication to mitigate the side effects. When it is no longer effective, we will have to look at other options, but I am so fortunate to have made it this far. Unable to work due to ongoing treatments and fluctuating blood counts, I

37 CAREGIVER STORIES

OUR CAREGIVER STORIES

were able to get him to these two facilities MY HERO there was nothing more they could do for him. SUSAN URBAN My father got progressively worse and Carlsbad, California his quality of life was nothing. He decided I would like to take this opportunity to he had had enough and he refused any tell you about a very special man that was more treatment. in my life, he was my hero, he was my Then on November 1, 2012, my hero, father. My father was born and raised in this man that had been my source of Los Angeles by his parents, two Italian strength for so many years, was taken away immigrants from Italy. My father always from me by this ugly disease, MDS. While wanted to be a firefighter with the Los running the support group in Oceanside, I Angeles City Fire Department. He was a organized a blood drive with the San very special man, and always had a desire Susan and her father, and hero. Diego Blood Bank and we had a huge to help his fellow man. Then World War II success in getting a lot of blood donated broke out so my father enlisted in the father did not lie very well and he told me and it was marked to be used only for MDS United States Navy. He served his country “Oh, he does other things besides patients. My only regret is that my father well as a machinist mate 2nd class aboard oncology”. I’m thinking to myself “no way”. passed away two weeks before we had the the USS Bliss (a troop transport). After the After visiting with my father, I went home and blood drive so he could not see the amount war, my father worked odd jobs until he immediately called my brother and told him of people who so generously donated their was able to live out his dream of becoming what dad had said. I told my brother that blood to help people they did not even a Los Angeles City Firefighter. Whatever something wasn’t right. After my father got know. I was overwhelmed by the amount job my father held, he put his heart and out of the hospital my brother and I went over of Marines that drove by the donation site, soul into it and did the best job that he to his house and confronted him about what saw the sign and stopped to donate blood. could. He lived, breathed and ate the Los I heard him say in the hospital. It was then It kind of came full circle. Here were men Angeles City Fire Department. He made that he told us that he had MDS and had had defending our country (as my father did many friends on the job and truly believed it for 4 years already. We asked him why he during WWII) and now donating blood to in “The Brotherhood” that firemen have. didn’t tell us that he had it and he said “I help people they didn’t know (like my While on the job, he worked side jobs such didn’t want people to feel sorry for me”. father helped people he didn’t know by as he was the safety officer when they I started finding out as much as I could putting out fires in Los Angeles). I contacted dynamited Chavez Ravine and built what about MDS and that is when I found out the Oceanside Fire Department and shared is now Dodger Stadium. The fire that there were no MDS support groups in my father’s story and that he would be so department. was also responsible to have Southern California. I wanted my father to proud if the fire department participated in a fireman as a safety officer on movie get as much information about the the blood drive in some way. They very locations and my father worked with the disease and by starting the first Southern generously sent a vintage fire truck likes of John Wayne and Kirk Douglas. He California MDS Support Group in manned with firefighters to the blood loved his job. He remained on the Los Oceanside, I was able to get a lot of donation site, and stayed for the entire time Angeles City Fire Department. for 25 years great speakers who had some valuable speaking with everyone and letting them until his retirement in 1977. It wasn’t the information. I not only wanted to help my take a look at the fire truck. I was very job that made him retire, he was tired of all father but we had a great bunch of touched by their generosity. the traffic and smog that comes with living people in our support group who became I am now in charge of a new MDS in Los Angeles. It was his time to relax and “my family” and I wanted to help them as Support Group and we meet at St. Patrick enjoy his retirement in Carlsbad, CA. He well. I couldn’t stress enough for the Catholic Church in Carlsbad, CA. I also still stayed connected with his “firemen” members (including my father) to go to an planned another blood drive on November buddies and would meet monthly with a MDS specialist not just a general 16, 2019 and invited the Carlsbad Fire group of them for breakfast and talk about hematologist or oncologist. My father had Department. The public is grateful for all the job. Once a fireman always a fireman. been going to a general oncologist who that firefighters do and it drew a lot of Sometime around 2009, I went to visit my basically just gave my father over 80 people to donate for those deserving father in the hospital and overheard he and blood transfusions, which gave him iron people who need it to live. It was icing on my mother speaking about seeking an overload. My brother and I took our dad the cake as some Carlsbad firemen also appointment with an oncologist. The word to the City of Hope and to Moores Cancer came and donated blood in honor of their “oncologist” stuck in my head and I asked Center for second opinions, but by the fellow firefighter, my father (Remo Tersolo), him why he had to see an oncologist. My time we knew of my dad’s disease and my HERO. The Brotherhood...

38 OUR CAREGIVER STORIES

the foundation posted information about A LITTLE DIFFERENT STORY our group on their website and on their LORI NELSON social media platforms and sent us a box Burnsville, Minnesota of great materials to distribute, and I Two years ago, my husband Curt (74 bought cookies. And yes…they came. years old) was told that he had MDS. Our group of 15 meets 4 times a year What was this new chapter in our lives?? at the library community room. We share Did we know anyone in our circle of treatments, favorite medical teams, and friends who we could identify with? Did tips to endure transfusions and treatments. anyone have knowledge or tips for us? One thing we have in common is that we Turning to the internet, I found the MDS know no one, outside of the support group, Foundation and reached out to them. who has MDS. It can be a lonely walk with Wonderful material resources soon arrived MDS so it’s so important to know that you in the mail; however, we came to find out are NOT alone. that there weren’t any MDS Support At this time, my husband’s blood counts If you live in a state without an Groups in our region of Minnesota. The are high enough to not require any treatment. MDS Support Group just buy some MDS Foundation, Patient Liaison, Audrey We are privileged to know this wonderful cookies and find a community Hassan, suggested “YOU could start one.” group of caring and supportive people. space…and they will come!!! ME? Maybe we could! What would we need to facilitate a meeting? Audrey MINNESOTA MDS SUPPORT GROUP: The Minnesota MDS Patient suggested that we first find a meeting place Support Group meets quarterly 3:30 PM at Burnhaven Library Main Meeting and that the MDS Foundation could help Room, 1101 County Road 42 W, Burnsville, MN 55306 (corner of Burnhaven provide startup funds that could be used to and Co. 42). Contact Group Leader, Lori Nelson at 952-892-3659 or email buy refreshments. We placed a few [email protected] for upcoming events. meeting notices in the local newspapers,

NEW MDS SUPPORT GROUP TOOLKIT NOW AVAILABLE ONE OF MDSF’S GOALS IS TO EXPAND THE NUMBER OF SUPPORT GROUPS WORLDWIDE

We are always on the lookout for people who are willing to start a group, offer some support in their area, and widen our support services to include more individuals affected by MDS.

We want to make it as easy as possible for volunteers to create MDS SUPPORT GROUP and run support groups to ensure they can provide continuous LEADER’S TOOLKIT comfort to those utilizing them. A Helpful Guide for Support Group Leaders Support Group Leader Toolkit We have created a that will The provide guidance on how to run the group, suggestions for Toolkit, along with discussion topics, useful tools like sample letters and forms, downloadable sample forms can and various other resources to help the meetings run smoothly. the myelodysplastic syndromes foundation, inc. be viewed www.mds-foundation.org online. If you are interested in starting a support group of your own, please contact Audrey Hassan at 1-800-MDS-0839 Ext. 210 or email [email protected].

39 AML CORNER

AML PATIENT STORIES

YOU AND AML: AN ANIMATED PATIENT’S GUIDE TO ACUTE MYELOID LEUKEMIA This resource is intended for patients with acute myeloid leukemia (AML). You will find expert advice about AML, AML with myelodysplasia-related changes (AML-MRC) and treatment-related AML (tAML) to help you discuss key issues with your healthcare provider and make important decisions related to management and treatment.

"YOU AND AML" CONTAINS 4 LEARNING MODULES: EACH PATIENT HAS THEIR • Understanding AML • Diagnosing AML, AML-MRC and tAML • Understanding AML-MRC and tAML OWN UNIQUE STORY • Treatment of AML MEET AML PATIENT Each module contains easy-to-understand animations with audio narration, video VALERIE FONS explanations by AML experts, patient interviews, and illustrated slide shows.

SURVIVOR Surrounded by the Atlantic Ocean and the Caribbean Sea is the Island of VALERIE FONS Hispaniola and the town of Puerto Plata. Washington Island, Wisconsin When my canoeing partner and I landed God on high, hear my prayer, at this seaport town, we had already In my need, you have always traveled nine thousand miles in our solo been there. canoes from the Arctic Ocean enroute to Cape Horn, Chile. I sought the cool He is young, he’s afraid, let him rest, peace of sanctuary and walked down a heaven blest. street paved in dirt, bordered by open Bring him peace. Bring him joy. sewer ditches to a stone building with the He is young. He is only a boy. sign of a cross. Let him live. On the steps of the St. Philip You can take. You can give. Let him be. Cathedral, women are holding babies. Lame, and diseased, with bleeding sores Bring Him Home, Les Miserables on his leg, a man sat on the steps with his open palm propped on his bent knee.

40 AML PATIENT STORIES

Small children stand with distended disease blooms past acute to severe and bellies, not playing but quiet, watching. HOW MUCH COULD I GIVE? chronic. Dr. Sandeep Jain, the ocular All have eyes of longing. Each hand is GVHD specialist at the University of outstretched in need. I walk between the I HAD ANSWERED THAT Illinois, Chicago, evaluated my Ocular people, through the open wooden doors, QUESTION WHEN WE BEGAN. Surface Disease Index score at 83.3 with onto the marble aisle, making my way to a symptom intensity of 6/10 termed the altar where I kneel and thank God I WAS GOING TO GIVE “Distressing/Miserable.” My tear pro- for our progress to this island. EVERYTHING I HAD. duction is zero, injured beyond repair. I The journey has not been easy. There invited the Wisconsin Department of were landslides on the Mackenzie River, YET, EVERY MOMENT I WAS Human Services, Office of the Blind and Vision Impaired when I was at the mercy Northwest Territories, Canada. My ASKED FOR MORE... partner broke ribs near Ft. Simpson. of state services and contributions of Inebriated locals chased us at Red Dog. THE JOURNEY HAS NOT adaptive equipment so I could know We were frozen to the seats of our what time it is. In a world of pain and canoes in Keweenaw Bay, spooked by BEEN EASY. blur, I learned to close my eyes and listen alligators in Florida, and paddled nonstop more intently. Asking my children to read to me. Drive me to an appointment for fifty hours on an open water crossing in At times, the expedition itself pressed because I am no longer able. Hoping the Caribbean. There were ten thousand like a throng of beggars. During the thirty- doctors do their homework. Panhandling miles of water still ahead. In the cathedral three-month journey, the question was the for persistent, dedicated researchers. at Puerto Plata, I breathed deeply. The same; how much could I give? I had Scrounging for clinical trials. Entreating furrow on my brow that was becoming a answered that question when we began. schedulers to find an appointment for me characteristic facial expression began to I was going to give everything I had. Yet, with the next recommended expert. relax, for I had escaped the noon heat and every moment I was asked for more. felt that at this moment there was no threat. Seeking Angel Flights and the kindness Twenty years after reaching Cape of volunteers, friends, and family to When I stood from the prayer rail to Horn, I was diagnosed with ALL. A bone deliver me to medical centers. Becoming leave the church, a woman came behind marrow transplant gave me six years a vagrant, waiting for the lab tech to go me and touched my arm. When I turned before the treatments I had endured easy with the stick and promise not to toward her, I could see her hand open induced MDS. I became transfusion fish with the needle. “Draw blood the and waiting for help. My spirit was dependent. When MDS morphed into first try,” I tell them. “Use heat compress refreshed by a time of prayer, I reached AML, doctors recommended salvage into my pocket and gave her a coin. chemotherapy. In 2018, with 40% When the money touched her palm, leukemia blasts in my marrow, I traveled she opened her mouth. In the dimly lit to the University of Washington Hospital church, her jaws became like a cavern of for a clinical trial named G-Clam Long anguish that seemed to swallow all Arm, endured a radioactive isotope remaining daylight. She had no teeth clinical trial as the first woman in the trial and her wagging tongue vibrated with following rats, dogs and three men. Full the sudden energy of a rallying cry. The body radiation was followed by an woman called her friends. I had been unrelated donor stem cell transplant. singled out as one who would give. The journey has not been easy. The Immediately, a throng of beggars beggars I encountered in the church pressed against me, all wanting help. I during my paddling journey? I am one of drew back and escaped into the street, them now. I have eyes of longing. I am hurrying away, sure that I was not meant on the take with my palm open, hand to provide for all these people. out, arm raised, and life at stake receiving the sacrifices of bone marrow and stem cell donors. I beg my donor Valerie checking into University of Washington cells to go easy on the attack mode Hospital for salvage chemotherapy with within my system as my graph vs. host GClam LongArm clinical trial.

41 AML PATIENT STORIES and tourniquet,” I suggest to the voice and body to be counted rather phlebotomist since I know my body best. than submitting as a data point, guinea When my port, double lumen Hickman, pig, or lab rat. I beg the pharmacist to and PICs are removed, leaving one, tell me the side effects of each new reliable soldier vein, I strive to place my medication even while the doctor orders arm in the best possible position to help the drug, upholds protocol, and cautions the clinical pierce my skin and draw the downside of not swallowing the enough to fill the red, green, purple, elixir. I beg for peace and understanding gold, and/or blue cap tubes with to accept my new normal even as I doctor’s orders. I rattle the cage when a recognize the dynamics of apogee – the test resultant is not forthcoming. I developmental culmination of the moon demand another provider when the orbit in the position farthest from the lumbar puncture goes bad with my body earth – seeking orientation in my position curved in a fetal position, facing the wall as cancer patient in territory I had never on the procedure table as the first imagined or asked for while struggling to assigned provider pokes multiple stabs find baring and purpose for my altered without finding the open space between life farthest from where and what I knew vertebra. I ask the nurse to hold my hand myself to be before cancer. as the doctor begins pressing my pelvis Grace is abundant. Without asking, I to find where to place the needle for a am showered with cards, prayers, bone marrow biopsy and aspiration. I cancer caps, wig, lap robes, smiles, beg my health insurance not to run out. encouragement, demonstration and the When I am in the hospital, I beg to return practice of courage in the world of home. I hope for a twenty-dollar bill to cancer survivors, caregivers, and surface in my wallet, or a credit card that donors. MDS Foundation, Be the Match has not maxed its limit to meet another Foundation, American Cancer, Blood co-pay or call a specialty pharmacy to and Marrow Transplant Info Network, extend credit. I track down social and Leukemia/Lymphoma Societies are workers for food, gas gift cards, cab sources for newsletters, webinars, vouchers to still the tide of my conferences, websites stocked with Halloween at the hospital. Valerie dressed evaporating finances. I rustle grants, with Survivor t-shirt, carrying a bag of her information, free counseling, referrals, heat credits, food stamps, and loans, empty medicine bottles, using a barf bag to grants, and more. Do people bearing tapping the equity of my house and car collect candy gifts, institutional staff and volunteers to pay the bills. I sit across from hospital financial aid officers making appli- cations for reduced or waived payments on my bills. Instead of a princess sticker as reward following procedures, I squirrel away juice, cheese, and snacks to bolster my food security. During infusion procedures, I ask for double the snacks I can eat and stuff my purse for treats to munch on later. I seek bargains on clothes and shoes for me and my children at rummage and garage sales. I bargain with myself to get out of bed, beat the incessant fatigue and flex my steroid melted muscles, stripped bones, frayed joints, and fragile, thin skin Valerie's bone marrow biopsy enroute to lab for testing compromised by treatment. I beg for my

42 AML PATIENT STORIES realize their work and kindness are critical for so many of us? People tell me they do not like asking for help, and prefer independence. I remind myself and other advocates of pulling oneself up by bootstraps that we are conceived dependent in our mother’s wombs. We are born dependent. Surviving cancer is a great equalizer, dependent on the kindness of others even when we hide in bed with covers pulled over our heads, exhorting the world to go away, while grappling with the necessity of support teams and wondering who amongst family and friends are willing to come alongside. Sometimes I notice a new best friend in the patient beside me. We are two bald Honorary Black Belt, presented to Valerie by heads speaking cancer language. Gary Vernon with a certificate of Taekwondo I cry out to God for another day of Rank for loving service to others, lifetime accomplishments and indomitable spirit in being alive. I beseech thee, O Lord, for the face of great adversity. Signed by mercy. Victim is not the word I use or the Grandmaster Joseph L. Connelly, Seventh Self portrait art therapy at University of place I want to be. In the midst of my Degree Black Belt US Moo Sui Kwan and Washington Hospital. Gary Vernon, Second Degree Black Belt. circumstance, gratitude is bedrock and overarching privilege on the journey to healing. Begging that I can take up my well-being. I advocate for wholeness and pallet and walk with the army of survivors moving forward into a new day. Cancer reminds me of my 21,000-mile canoe journey from the Arctic Ocean to Cape Horn. During my decade of cancer and treatments, the question is the same. How much can I give? I am giving everything I have, even as every moment I am asked for more. And, I am receiving more love, learning, and care, while energized with a rallying cry of thanks!

Valerie Fons is a cancer survivor of ALL, MDS, and AML, a bone marrow transplant in 2010, and stem cell transplant in 2018. Diagnosed with MDS in 2016, doctors told Valerie she was dying. In response, she wrote lyrics of affirmation and life set to the melodies of popular show tunes. The American Transplant Games heard Valerie’s songs and accepted her as a participant at the 2020 games in the vocal lyrics category. In July, 2020, she will be singing her good marrow songs in Meadowlands, New Jersey. She lives on Washington Island with six adopted Valerie and her son Joshua at Leukemia/ children, her husband Joe, and a dog named HOPE. Lymphoma Society Light the Night Walk

43 Do you...

ACUTE MYELOID LEUKEMIA also called AML, is a type of cancer that a ects the stem cells in the bone marrow. It is one of the most common types of leukemia in adults, but can develop in children too.

SIGNS& SYMPTOMS AML develops quickly, which is why it is termed “acute”, and is often diagnosed at an advanced stage. It is important @KNOW_AML #KnowAML for everyone to fully understand the signs and symptoms to ensure a diagnosis is made as early as possible. Here are some of the general signs and symptoms of AML to look out for:

Know AML is the fi rst global AML awareness WEIGHT LOSS and education initiative. Our goal is to facilitate TIREDNESS OR FATIGUE and improve AML knowledge worldwide and FEVER develop community-based initiatives to LOSS OF APPETITE overcome current and future challenges. NIGHT SWEATS For more information, visit: BLEEDING/BRUISING MORE EASILY

www.know-aml.com

44 MPN CORNER

MPN PATIENT STORY

MPN EDITION – BUILDING BLOCKS OF HOPE RESOURCE As a continuum of our efforts we have expanded our focus to include education and research into related myelo- proliferative neoplasms (MPN), the so called overlap syndromes, especially given their similarity to MDS in their clinical presentation and the mutations that accompany them. Our new MDS/MPN patient and caregiver resource, Building Blocks of Hope® MPN Editions, was completed to meet the needs of patients who are LIVING with MPNs. THE MPN BBOH OFFERS PATIENTS AND CAREGIVERS INFORMATION ON: • Understanding Myeloproliferative Neoplasms (MPNs) • Polycythemia Vera (PV) • Primary Myelofibrosis (MF), Post PV-MF and Post ET-MF • General Resources for Living with MPNs EACH PATIENT HAS THEIR • Essential Thrombocythemia (ET) OWN UNIQUE STORY MEET MPN PATIENT To view and download the MPN Edition of the Building Blocks of Hope go to: MICHELE RILEY https://www.mds-foundation.org/the-myeloid-continuum-of-diseases/.

sudden but brief chest pain in the middle of slow progressing. The bad news was that ME, GOD AND THE the night, I went to my doctor and said, there was nothing they could do about the CLEMSON TIGERS “Something is wrong”. The EKG was fatigue. It was now my new normal. My normal so my doctor sent off some blood doctor, Dr. C, told me, “Only God knows MICHELE RILEY work. The next morning she called to tell your expiration date. So go out there and Brentwood, Tennessee me that there must have been some error at live your life fully!” He told me there was Simply put, my cancer story is about the lab because the results were “weird”. promising new research happening which having faith and trusting your instincts. Of She wanted me to come back for a redraw. would hopefully mean treatment options in course there are many episodes and a Two days later she called and said, “Your 5–7 years. And stem cell transplant would be wonderful and important supporting cast repeat bloodwork came back even more our back-up plan. He thought I could coast and crew. I am the star in this story, but I abnormal. Your CBC is extremely elevated for 5–10 years. I decided I would look at my am also the director. My doctor is the and that means there is a hematological journey with optimism. My parents gave me director of photography. He has the event happening. We need to get you in to a T-shirt that said “Attitude is EVERYTHING! “vision” of how to orchestrate my treatment see a specialist ASAP”. Her voice faded Pick a good one!”. Instead of a dramatic plan. But all decisions are ultimately mine. and everything around me blurred into the single movie story with a sad ending, I was My best advice to you is: Always be the background. My Cancer Story had begun. going for a sitcom with many seasons. director in your story. In other words, My official diagnosis came in March always have an active roll. 2007 after a slew of tests. I remember the My story begins at the end of 2006. I lab tech making slides with my bone marrow found myself really struggling through the and wanting to grab them up and hide them. holiday season. I was 38 and finding it I knew people were going to look at those really hard to complete holiday tasks, do slides under a microscope and pick them my usual weekly errands, and work full apart and list all the irregularities and that time as a registered nurse. At first, I told made me sad. They determined I had myself, “Well, you are approaching 40. I Myelofibrosis (MF), the most serious of the guess this is to be expected.” But when I Myeloproliferative Neoplasms (MPNs). No still felt really fatigued after the holidays definitive cure or real treatment at the time. were over and I woke up a few times with The good news was that MF is usually very

45 MPN PATIENT STORY

In Season 1, I focused on learning new Eventually John insisted I join in and at least ways to stay as healthy as possible and pick a side if I didn’t have my own team to finding better ways to balance my life. The support. Simply to antagonize John, I said, season included a 2-parter where through “Okay, I choose the Clemson Tigers”. I a crazy turn of events, I found out Dr. C didn’t even know what part of the country and I both belonged to the same Clemson was in! I did a little research about meditation group. It always warmed my Clemson, SC, the University, Coach Dabo heart on the nights when I looked up from Swinney and the players. I started getting my cushion to find Dr. C on the cushion attached to those Tigers. I also studied the beside me. It was a hug from God. I felt rules of football. My intention was to learn confident in my team and treatment plan enough so I could adequately razz John. But and periodically God sent signs to reassure Clemson was doing well that season and I me. By Season 2, I had lost perspective of quickly got drawn in. I told him “We” how fatigued I actually was. I just went on (Clemson) had “Tiger Power” and we would living a crazy but very happy life. win the National Championship. The crazy I made it to Season 6 with very little was like a new beginning. Living a low thing is, WE did!! From then on I was change in my health. Then my hematocrit symptom life was AMAZING!! I was able hooked. I used the phrase “Tiger Power” to became really high and my very thick blood to volunteer as a mission nurse in Honduras proclaim the reason behind victories for caused me to be very fatigued. I began again, and run in 5K races. I did more Clemson or myself personally. #TigerPower going once a month to have 500 ml of traveling too. The great response to Jakafi became part of my identity. blood removed. I’d have to receive a fluid lasted through Season 10. And then the Now back to spring 2017. Things were bolus to replace the volume or I’d pass out. symptoms started drifting back and my changing and not in a good way. Dr. S I continued to feel weak, and the resulting blood started showing new changes. We gave me options. My gut said “No” on low iron from the frequent phlebotomies were at a crossroads. SCT. He had a brand new clinical trial that caused constant irritable leg syndrome. I Before I can tell you about Season 11, I he was especially excited about but he never slept well. Life was difficult. need to do a little recap. In summer 2016, was hesitant about enrolling me. The new Over time, my symptom load gradually when I still was in that low symptom phase, trial involved paring the Jakafi I had been increased and in Fall 2014 it reached a I was at work. My coworkers were taking with an investigational drug. These life altering level. Dr. C had retired and in discussing the upcoming season of college drugs had never been paired before, and a magical episode in Season 8, God football. John was being boastful about his Dr. S said there was a risk it could cause directed me to Dr. S. In 2015, Dr. S started Louisville Cardinals and Jenn was praising harm. A low risk, but still a risk. He did me on the drug Jakafi. It was one of the her beloved Clemson Tigers. I never had have a patient in the trial that had recently discoveries resulting from that research Dr. followed football of any kind, so I was not achieved remission, so it was worth at least C had told me about in 2007. Season 8 participating in their conversation. thinking about. I went home and started

46 MPN PATIENT STORY researching the investigational drug. It was there are messages for all of us to help not yet named so it was known by the guide us on our paths. alphanumeric the FDA had assigned to it. I Complete remission means complete didn’t notice it right away, but in the name cessation of symptoms. My CBC is now was a sign. When I saw it, I knew instantly normal and my precious bone marrow has that I had to enter that trial. The no irregularities for someone to list. I feel investigational drug was TGR-1202. TGR better today than I did in my thirties. I as in Tiger! It had Tiger Power!! God had remain in the clinical trial for now and set in place the series of events that led to recently passed the remission 2 year mark. my becoming a Clemson Tiger fan so I’d We are not sure what the future holds. We see the “Tiger Power” sign and not be will keep riding this wave for now. Season afraid of the clinical trial. It all made sense 12, 13 and now 14 is all about living a full that I had suddenly become a college life without limits. I joined Iron Tribe Fitness football fan at the age of 47! I told Dr. S and do High Intensity Interval Training (HIIT) my Tiger Story and that 2 was my favorite under the careful watch of my coaches. I number. “I will be Patient #2 in remission! run, jump up on boxes, lift weights and do “You just watch”, I told him. He chuckled real pushups! I also trained for and ran a and said, “Okay, let’s go for it!” I started half marathon. I celebrated my 50th the clinical trial in July 2017 and wore my Birthday in Ireland with friends. An MDS along with MPNs because they have Clemson Tigers T-shirts and sometimes tiger recently discovered that these diseases ears to my weekly clinic appointments. Dr. important Bucket List achievement. I overlap. They are like cousin diseases. So S calls me Smiley Riley, and soon the staff became a Clemson donor in 2018. College I started a private Facebook page called all knew about Smiley Riley in the tiger Football is now one of my passions. Me, ears who insisted she would achieve Jenn and John have started the tradition of Nashville MPN/MDS Support Group for remission. Everyone was so supportive! I going to the Clemson vs. Louisville game patients in Tennessee, Southern Kentucky, have photos of some of them in Tigers ears together with our families each season. Life Northern Mississippi, Northern Alabama too! By November, to everyone’s delight, I is good and full of new opportunities! and Northern Georgia. Right now we offer had, in fact, reached complete remission!! My doctor and I decided that we support via the group page only but we I’ve enjoyed telling my Tiger Story over the needed a patient support group in our part hope to hold meetings several times a year years. If you keep an open mind, I believe of the country. He wanted me to include once we have enough interest in formal meetings. I also plan to try Facebook live sessions in 2020 as an additional way to connect patients. I sit on the MPN Research Foundation Impact Council to help the MPNRF identify patient needs and provide feedback regarding projects and outreach activities. I recently attended an MDS Foundation Patient and Family Forum in Nashville to educate myself about MDS. I am hoping to find a few MDS patients in my area to help me with the group and to be administrators on the Facebook page. I have received so much support from so many wonderful people over the years. I would like to pay it forward and help as many patients as I can. One of the mottos at Iron Tribe Fitness is “Stronger Together”. I think that applies for Cancer patients too.

47 MPNFAMILY PATIENT STORIES STORIES

MDS/MPN-UNCLASSIFED only one Phase 1 trial in the country using them. The trial was at MD Anderson in AND THE SCIENTIST Houston. She contacted Dr. Naval Daver, JOHN SOPER, PhD lead investigator in the trial, and submitted Yukon, Oklahoma all of the data she had on my case. While I’ve been generally healthy for MD Anderson contacted me in just a most of my life, I’ve had several instances of couple of days. We drove to Houston, elective or emergency hospitalizations. The repeated all of my original testing and first of these involved a bleeding ulcer in confirmed all original tests. I returned to which my hemoglobin dropped to around Houston in two weeks and was now 6-7 g/dl. I was treated in a hospital in officially admitted to the study. I had an California, at the very beginning of the official diagnosis of MDS/MPN-unclassified. AID’s crisis. Although there were no tests for I have now had three months of Jakafi AIDs, I was going into shock and received alone, followed by another bone marrow my first transfusion. biopsy. After completing that regimen I had Christine and John Soper Several years later, I had another ulcer, three months of combined Jakafi/Vidaza and received my second transfusion. After with the anemia, seemed to be consistently therapy, followed by another bone marrow this I began being much more con- in the “Normal--Low Normal” range. biopsy. That biopsy showed no increase in scientious about routine physicals, and When we returned to Oklahoma City, blasts, and no evidence of a clonal became a 4 gallon Red Cross blood and Dr. Bova repeated all of her earlier lab neoplasm. In another month I will have a platelet donor. I was also continuing to tests, including a new bone marrow third “staging bone marrow biopsy”. battle lifelong weight, cholesterol and high biopsy. This time the results showed that I While my white counts are behaving blood pressure issues. had 4 mutations, as well as altered nicely, I am becoming transfusion depen- In January of 2014, I discovered that I chromosomal results. My LDH levels were dent. We have mutually agreed that a had atrial fibrillation. After running many substantially elevated, my neutrophil count hemoglobin level of less than 8.0 mg/dL tests, my cardiologist performed a continued to rise, and we were now warrants a transfusion. I have had about cardioversion to correct the issue. While detecting blasts in my peripheral blood. 8–10 transfusions at this time. My ferritin this seemed to be successful, a few weeks Dr. Bova wanted to prescribe “Jakafi” concentration is approximately 1,500 later I began experiencing some angina (Ruxolitinib), as well as “Vidaza” ng/ml. We are aware that Vidaza is like symptoms. After performing an (Azacitidine). She found that there was causing myelosuppression at this time, but angiogram, we realized that I needed a we are also confident that it will eventually quintuple coronary bypass. allow my hemoglobin levels to rise. A few months after surgery, my During my last visit with Dr. Daver, I was cardiologist told my primary care doctor, asking him a question about some of my that I had macrocytic anemia. My primary genetic results. He simply said, “You’re a care doctor realized that I needed to see a scientist, you’re aware of the statistical hematologist. variability in any laboratory measurements.” Dr. Abby Bova had already taken care It is very important to me that both of my of my wife’s breast cancer, and we knew Doctors value my input, and that I am that she we was the perfect fit for us. She involved in making decisions that all of us quickly ordered every conceivable test for are comfortable with. me, including a bone marrow biopsy. I’ve had the opportunity to be actively When my wife and I finally saw Dr. Bova involved with research at places like Johns she was literally beaming with joy! She told Hopkins, Mt. Sinai, University of Arkansas us that all of the tests were negative. for Medical Sciences, and the University of Unfortunately, I still had macrocytic Maryland. I can’t conceive of a better anemia. I would see her every three months, team, or overall medical care that I am and all test results, except for those concerned John with his youngest daughter, Dannie now getting.

48 MPNFAMILY PATIENT STORIES STORIES

Let me share some final quick comments long he had been treated, he told me that with you. I REALIZE THAT NONE he’d been receiving treatments for five (1). As I stated earlier, there are some years. I was really stunned to find that there particular things that I intend to do. I have a OF US KNOW HOW OUR was a fellow right next to me that had the very complicated initial diagnosis. As far as MEDICAL CONDITIONS very condition that I had thought was Dr. Bova is aware, I am the only person in supposed to be “the end of the road” for the entire 4 state Mercy medical system to MAY PROGRESS, MDS patients. He seemed to be doing very be receiving both Vidaza and Jakafi. I’m well to me! also the only crossover patient (MDS/ MPN) BUT WE CAN CHOOSE to be getting these medications. My clinical CLOSING THOUGHTS TO NOT LET THAT FACT trial lasts for five years, and hopefully I may When I think of the comments of my produce some interesting results by then. CONTROL OUR LIVES. “MDS buddies” I realize that none of us (2) There are also things that each of know how our medical conditions may you can do. First and foremost, your progress, but we can choose to not let that In many of your comments, and in “primary caregiver”, wife, husband, other fact control our lives. questions we’re asked during our treatments, family members, etc. are among your most For my part, I am preparing to retire, and we’re reminded that spiritual support is vital important assets. Always try to give them try to carry out some of the things above that to our well-being. Most of the places where as much consideration as they give you. I’ve already said that I can do. Frankly, the I’ve worked, or been a patient, offer not only Aggressively maintain the other valuable single most important thing that each of us superior medical care, but have direct contacts that each of you already have. I’m can do now is rejoice in each new day that Christian or Jewish institutional support. convinced that the level of achievement we’re given and “Make Memories”. that I was able to access in my early career My very close friend, and Laboratory Thanks for reading “my story”; I hope came from the fact that I’ve been able to Manager, Dr. Phil Kemp, leads a Bible you enjoyed reading it as much as I’ve maintain those contacts for many years. Study at the Federal Aviation Admin- istration. This is one of the most incredible enjoyed writing it! groups that I’ve ever been involved with. The Naval Academy Chapel was also a strong reminder of the importance of a “Spiritual Anchor” to our lives. Every day that I was a Hopkins fellow I would pass through the old main lobby, and see a 9-foot statue of “Christ the Healer”. While Hopkins represents excellence in medicine, this was a constant reminder that there is a power beyond even what the world’s best physicians can do. (3) Another very important support that you have comes from your fellow patients. My original “MDS buddy” (the same one my father treated many years before), told me when we first met “I have this tattooed on my forehead, the drugs work until they don’t”. Several weeks ago, two of us were getting Vidaza treatments. I asked the Sculpture of Captain Love, an elite navigator fellow next to me if he had MDS. He didn’t for the Army Air Corps in World War II. When we see him we know to turn to the right to go know what that was. I asked him why he to the hospital. I am posing in my Eagle Scout was receiving injections, and he told me “Navy” flight jacket. that he had AML. When I asked him how Christ the Healer at Hopkins

49 CONTRIBUTIONS TO THE MDS FOUNDATION

The MDS Foundation relies on gifts to further its work. We would like to acknowledge the generosity of the following individuals and organizations THANKYOU that have recently provided gifts to the Foundation: Roger and Diana Abbott Diana Blair John and Alice Carlstrom Fred and Carol Coyne Barbara Ackley Bernard Blessinger Rosalie M. Carothers Mike and Pat Crilly John Adams Katherine Bliss Allison M. Carroll Matthew Cristadoro Amelia Adams David Blivaiss John M. Castner Jeffery Kahn & Genie Croft John Adams Duane Bogenschneider Tony Cervone Ed and Pat Crowe Joni Adams Marian Bond Belinda Chadwell Maureen Crowley Marcelle M. Adams Don Borth Daniel Chambers Neil and Ruth Cuadra Mark and Deb Adkins Diane Boyer Jennifer Chambers Sylvia Curtis Rich Ahearn Zay and Cinnamon Bradley Kevin Chambers David Cushman Phyllis Allen Demos Brands Meghan Chambers Mark Cushman Edward J. Allgeier David Bremm Victor Chang Rita & Bruno Dacanay Rob Allred Elizabeth Brennan Antonia Charles Raymond P. Daniels Brian Scott Anderson Mary Bressette Mary & Leo Chimienti Mariana Daniels Judith Anderson Diane Brizer Randolph & Elizabeth Chinyee Peter Danielsen Barbara and Charlie Anderson Logan Brown Mary Choplosky Douglas & Kristen Davenport Rodney Anderson Sally Brown Rebecca Christianson Jennifer Davidson Doug and Carolyn Andrews Nancy Bruch Michael and Joann Cinque Vickie Davidson Angel’s Security Corporation Dennis and Barbara Bruns Sarah Cissna Peggy D. Davies Jennifer Angove Ian Buchanan Citizens Deposit Bank John Davis Glen D. Aspinall Janice Buckner Curtis Clark Trevor Davis Merry Atwood Theodore and Linda Bucon Virginia Clark William Bell Davis Kenneth N. Baker Charles Buess Victoria Clifton Vernicia Dawson Grace Baker Lori Bungarz Thomas Coccagna Linda Day Stacey Baker, PhD Donna, Dave and Davy Bunton Alexis Cocco Andrew Dayney Charlie Balstad Melanie Burch Lowell Cohen Kevin De Sa Anthony W. Barker Ruth Burgess Amy Cole Deborah Dean Claude and Maryann Barone Richard and Ann Burgy Cheryl Coleman Sandra, James and Sara Dino and Gloria Barone Carol Burns Robert H. Collins, Jr. DeCarle Barbara Bartlett Michael Busalaki Conklin Ella Mobley Deese Lawrence Bechler Robert and Ellen Busch Seraphin Joseph Conley Mary Deming Jack Becker Jennifer Buxtin Connie Connely Lauren Dennis George Beeman Doris Faye Byer Kathleen Connoy Kyle and Kristin Denton Tony Bell Michael Byers Adam Considine David and Mary Deucher Marie Belpulsi Kasha Cacy Rose and Ron Conti Sheila and Marci Deyo Raymond Michael Bennert Amanda Cadle Doyle C. Cook Melanie Diamond Dr. John M. Bennett Giovanna, Brendan & Bruno Caffrey Marilyn Copeland James & Josephine Diedrich P. Bruce Benzler Anne Cahn Norma L. Corbin Dennis D. Dillon Stephen John Berger, Sr. Louis Camhi Marissa Cortese James and Ann DiMattia Marvin Berlin Patrick Cammarano Joseph and Marion Cotton James and Meg DiMattia Robert Bernhard Maria Campano Ashley Coulter Joan Dion And Family Joan Bersofsky Vicki Capp Ann Brody Cove Shereen Docktor Beth Birnbaum Justine and Joe Cardone Jeff and Cheryl Cowan Jennifer Doggett Naomi Bisk Dorothy Carlisle Marianne Cowing Mark Doherty

50 CONTRIBUTIONS TO THE MDS FOUNDATION

Nancy and Larry Dolph Dave Fisher Catherine Goff Jim Heiland Gayle Donaldson Linda Fisher Dr. Stuart L. Goldberg Paul and Julie Hellenbrand Paul Donovan Philip and Myra Fishman David Goldberg Freyja Helmer-Sindemark Ted Dorf Kathy Flaherty Lewis and Sylvia Gollub Heidi Helmich Stan and Suzanne Dorf Nancy Fleming Hayden Gomes Raymond M. Hencken Advised Fund of the Jewish Dorothy J. Flett Marsha Gonda Christine Miller Hendrix Community Foundation Emil Fleyshman Matthew Gonzales Arnold J. Henig Elizabeth Doriot Lewis Flock Goodman Real Estate John Hennessy Lea Dottke Ekaterini Fokas Services Group David Hensel Kristin Dowling Bob and Gerry Forster Judy Goodyear Kay Herrmann Nancy Downes Fort Sanders Regional Medical Rick and Sue Gordon John Heveran Melissa Drahzal Center Case Management Dept. Susan Gorenflo John Hindes William C. Drotleff Nicolas Fosdick Ilsa Gottlieb Diane Hinojosa Karen Dumas Thomas Frank Laura Lee Gramstad Brent Hladky Sheryl Dunsmore Patricia Freudenburg Granby Memorial High School Katherine Hobbs Theresa Duran Elizabeth Frey Field Hockey Program Fae L. Hoffman Regina LaRosa Durante John and Beth Frey Stancey Granger Stacy Hoge David Dyson Robert and Sara Frey Jerry and Renee Green Thomas and Betty Holder Victoria Connor Eagen Melinda Friedeberg Dr. Peter L. Greenberg Michael Hollander Barbara Earl Susan and Allen Frisch Trina Greene Carol Holman Henry Earl Joseph and Patricia Fritz Eugene Gregory Sara Holmes Douglas Edmunds Anita Froistad Teresa Gregory Anna Holness Meriam Eklund Nancy Gabriel Patricia and Brenda Grell Adrienne and Ira Holtzman John Elley Nancy Galba Elizabeth Gretton Ellen Hooley Jean Ellis David Galli Dwight Griesman Bill Hopkins Nancy Ellis William and Norma Gangloff Victor Groner Melinda Hopper Doris Emmons Michael Ganley Theresa Gross Cora Horton Richard Epler Jerrie Gann Vesna Grujin William and Barbara Howard Mary Epstein Bonny Gantz Amy Gustafson Robert and Kathleen Howell Ernsteen Family Foundation Kathleen Gauthier Robert Hackworth Antoinette Huber Randi Falow Margaret Gavin William Haeger Cecelia Hudzik Susan Fast Joan R. Callaway and Stacy Hagemann Paula Hultman Ellen Faulds Julie C. Geddis Louise Hahn Sharon Hunt Mike and Louise Fedora John Bovair and Dave Gentry Larry E. Haigh Richard and Sally Hyatt Janice R. Feely Tammy Gerber Robert Halleck Sandra Hynes Jane Felder Ulrich Germing Heather Hargrave William R. Iber Laurel Feldman Peter Gettner Harleysville YMCA Sharon Ingraham Mike and Susan Feldstein Steven and Beth Gilford Early Childhood Center Chris Ivanonko David and Shirley Fenner Gary Gillen Judy Harrelson Keith Jackson Carmen Fernández Ron and MaryBeth Gilligan Paul Gish Harvey Barry Jacobs Robert Ferone Richard Ginsburg Mitra Hashtroudi Claudette Jacobs Fertig Freedom Foundation Thana Giridhar Jonathan and Mandy Hasty Lauren Jacobs Andrew O. Feuerstein Paul Glickman Theron and Brooke Hatch Herb and Beverly Jacobson Susan Feulner Jeffrey Glover Sue Hauck Judith Jager Alicia Finnegan James and Judith Gmiter Robert and Judith Haynes Rachna Jain

51 CONTRIBUTIONS TO THE MDS FOUNDATION

Keith and Joan Jansen Meryl and Mark Klein James Lovell Patricia Meling Jay Jeffcoat Richard Klein Trisha Ludlum Danise Mena Thomas and Patsy Jenkins Bob and Laura Koestner Cheri Lundblad Raul R. Mena Tony Jensen Adam Kohrman Bill and Kathy Lyons Ana Merchant Louis and Kathy Jerge Mary Pat Kollitz Dorothy MacCormack Wayne Metsch Jewish Community Foundation Marjorie Kosic Janet Magnemi Gerry Meyer of the Milwaukee Jewish Karen Kramp Louis Mahaffey James Meyers Federation, Inc. Sandra K. Kratz Cathryn Majchrzak Russell Miah Leonard A. Jewler Donna Krauss Edward and Carol Major Beth Micenko Pam Johnson Ramesh Kumar Giuseppe Mallimo John Michalec Rita Perisin Johnston Michael Kurman Allan Malvicino Marcelle Michalski Cecile Jolin Rick and Lori Kurosaka Julie Manas Charlotte Milan Gregg Joly Robert Laccone David Mandell Helena Miley Diana Pappas Jordan Lake James Breakfast Group Phyllis Mandell Tessa Millard Diana Jose Leonard and Dolores Landi Ambuja Manoharan Bruce Miller Charlotte Joynt David Landis Mary Jane Marculaitis John Miller Wade Judge Judith Lane Marlene Marcus Lois Miller Linda Kaase Joanne Lasley David & Mitchell Friendburg, Lynn and Steve Miller Amy Kahn George Latsko and Alan & Alissa Margulies Malcolm and Marilyn Miller Jeffrey Kaminski Susan Laufer Linda Marie Milt Miller Victor and Barbara Kaminski Joyce Law Peter Mariniello Ned Miller Jeffrey Kane Kevin Lawlor Richard Marks Betty Jane Mincemoyer Phyllis Kaplan Thomas Leclerc Jerry and Anne Marquardt Lynn Minnis Diane Kaufman Connie Lee Susan Marr Scott Mitek Sharon Kaye Ji Young (Claire) Lee Sheila L. Martin Mary Miyawaki Michael Keefer Nina Lee Susan Martin Yasushi Miyazaki Attila and Jana Kekesi Patricia LeHoullier Pat Marzetta Kenneth Mock Vasken Kelerchian Leon Lejda Deanna Masgay Jo Linda Moore Elizabeth Kennedy Marjorie Lejda Harriet Mass Kevin Moore John J. Kennedy Lisa A. Lenhart Thomas Matkins Susan Morales John Arthur Keough Frederic and Kathleen Leverenz Paul Maynard Jim Morelock Robert and Andrea Kerlan Resa Levy Anthony & Brenda Mazzocchi Beverly Morhange Phyllis Kerr James Lewin Jane McAuliffe Deborah Moroney John and Mary Khym Robert Lewis Larry McBride Timothy P. Morris Sally Killick Suzanne Lewis Bob McCabe Judy Morvay Phil Kimball Joey Lindstrom Ann McCarthy Edith Ann Mrazik Alexis Kimber Andrew Lindvall James R. McCloud Pamela Mroczkowski Steve Kincaid Irwin List Daniel McCormick Matthew Mucci Kimberlin Kincaid Mark R. Litzow Debra McDermid Harriet Muir Steve Kincaid Rebecca Long Mary L. McGrath Jane A. Mullen Michelle King Salli and Al Long Julia McGuire Bonnie Murphy Walt Kirchner John Loper Jennifer McInnes Joan Murray Ronni Kirsch Rocco LoPiccolo Marie McJilton Joseph B. Murray Janet Klagholz David Lorah Nina McSherry Bobby Myers Adrienne Klein Michelle Lord Roger Meessen Susan Natali

52 CONTRIBUTIONS TO THE MDS FOUNDATION

Dennis S. Neier William Pesek Bob and Marcia Rider J. Thomas Williams, Jr. Marisha Krupkin & Peter Kim – Erin Riggle and Nancy R. Schauer Dennis Neier Eastern Corporation David & Mary Ann Roberge Maria Schawiak Curt Nelson Bart and Laura Peterson Esther Rogak Loriann Schenking Mary Schmidt Dr. Stephen D. Nimer Edward and Angela Petranto Teresa and Scouty Rogers Helen Schoen Suzanne Nixon Lauren Peyton David Romano Joan Schoolcraft Edmund Oasa Murray Peyton Joan Romano Robert and Sally Peyton Julia Schuette Scott and Annemarie Oats Mary Romano and Family Jennifer Phillips Peter Schulkin Carolyn O’Brien Soo Romanoff Merle Phillips Mike and Toni Schwab Mary O’Connell Sara Ronten Debbie Pianin George and JoAnn Scimanico Susan O’Connell Janine Rooney James J. O’Donnell, III Karen Pierson John Scola Harvey Root Kevin and Jean Scroggin Office of Animal Welfare Gina Marie Pitti Barbara Roper Alan Seaman James O’Gorman Michael and Donna Pizzulli Charles Rosen Lynn Seidler Jesse E. Oldham, Sr. Mary E. Plante Harold M. Rosenthal , MD Craig Seifferth Eleanor O’Leary Julie Platanias Marian Rosinsky Terry and Carole Seiter Bernard Olsen Jane E. Pope Mark and Sheila Rosler Ruth Sencio Ken and Sherry Olson Brian Potter Debra Ross Heidi Senick Amy Oseland Marcia Powell Milton Ross Senn 61 Reunion Committee George Ossman Eddie Preijers PJ Ross Suzanne Sepety Ernest and Dolores Ott Hendrik and Diane Preijers Ginger Y. Rosser Elaine Serina Mark Owen Thomas J. Preston Charles Roussel Eugene Serina Shelly Purcell-Owens Mike Price Kim, Todd, Alexis & Tyler Rudolph Mike Seyler Marilyn Painter Judith M. Price Frank and Mary Ann Rusignuolo Patricia Seyller Frank and Eileen Palmieri Joyce Printz Patti Ruth Stephanie Shaffer Steven and Vickie Paluska Geoffrey Propheter Toni Ruth Kathy Share Paoli Hematology Oncology Jeff Quaintance Ann Sharon Associates, PC Lauren Rutigliano John Kaase Racing John Shea Elizabeth Papetti Sean Ryan Alaric Radosh James and Barbara Sheehan Jill Parker Michael Sabloff Katherine Radosh Ron Sheets James Patrick Connie and Roger Sakash Kathleen Ramassini Karin Sheridan Elizabeth Patterson Dan and Risa Saltzman Kim Ramer Jack and Grace Sherman Marija Pauly Janet Sammarco Clement and Joan Rancourt Jane Sherman Brian Pearce Jim and Judith Sandler Teri Rankin Julie Shervey Isaac Contreras Sandoval Steve and Rosemary Pearson Marlene Hoffman and Stacey Shoaf Michele Sangataldo Richard Pegg Brett & Jayme Rapp Lori Sholota Srinivasa Reddy Sanikommu Deborah J. Peirce David Rascher Karen Shover Monique Della Santina Barbara Peixoto Maureen Ratliff Tim and Lynne Shuey Lorenzo and Joan Sharon Pelosi Jeanne C. Rechenmacher Darlene Sarne Jean Shumard James and Susan Peluso Rick and Sandra Reed Marlene Sauer Terry Siegfried Dolores McDonald Pendell Loretta A. Reiner Abigail Savage Steven Siehr Russell Pennelly Louis Resnik Dr. Michael R. Savona Morgan Simon Pennsylvania State Police Sandra Rexroat Charles Scaief Suzana Simonishvili Nick Perisin, II Mary J. Rhoads Ron Schachtel Earl Simons Brett Peroni Thomas Richardson Jesse and Elaine Scharf Kevin Sindelar

53 CONTRIBUTIONS TO THE MDS FOUNDATION

Barry S. Skikne Advised Fund of the Jewish James and Evelyn Robert Williams Ed and Bette Skok Community Foundation Marcie Vinson Tiffany Williamson Claire-Elizabeth Sloan George and Rosemary Swantek John F. Voit Ralph Wills Kim Slota Aggie Sweeney Muriel Vosko Boyd Winck Billy Smith Kimberly Sweeney Donlon Wade Page L. Wingfield Nichol Swenson Fred and Rosalee Smith William and Alice Walfoort Kenneth & Patricia Kim Tardy Winkelvoss Linda Smith Jake Walters Ann C. Taylor Edward Winn Lois Smith Fay Wanetick Deborah Taylor Maureen Wirth Renate Smith Suzanne Ware Richard P Taylor William Wisneski Diane Sobel Elizabeth A. Wargel Gods & Heros Tenace Hubert and Sophia Brian Sode Peter Warner Mike Tersolo Wisniewski Theresa Soderberg Carolyn J. Warren Jerry and Judy Tetley Mary and Mike Wolf Cynda Solberg Matthew and Sherry Warshauer Heidi Thacker Bob and Barbara Wolfe Ronald Solberg Warthogs Motorcycle Club The Garden Club of Mansfield Mt. Clemens Chapter Charitable Fund of the Ronda Solberg Princeton Area Community The Henry and Marilyn Taub Virginia Watson Suzanne Soltysiak Foundation Foundation Karen Webber Women of the Moose Maxine Sortino The Lester and Grace Maslow Stephen Francis South Greenville Pam Sparkman Foundation Jim and Patti Wegge Chapter 1552 Louise Spedaliere The Philip and Myn Rootberg Diane Weidenbaum Randall Wong Don and Janet Speer Foundation Debra Weiner Mary Linda Wood The Tom and Nancy Bruch Fund Frank Spink of InFaith Community Foundation Claire Weiss Catherine Woods James and Jane Springer The Wolterstorff Family Leon Weiss Eileen A. Woods Mary Spruil Kathleen Thesing Joan and Gene Welch Susan Woodward Eleanor Spuhler Carol and John Thiel Doris Welsh Joan Woolson William Stanbach Jerry Thompson Stacy and Pamela Wenzel Marie C. Wright Stanrose Foundation Barry and Mary Thompson JoEllen White Marek Wulw Lawrence Staudt Pat Thompson Veramae Whitlow Ross Wyman Carla Steger Dale and Judith Thorne Pam Whitmore Qing Xu Kathy Stegh Angeline K. Thorner Martina Wiedmayer Kiku Yamada Constance Stephens Kristen Thornton Jack and Kimberly Wildes Linda and Bob Yonke Joan Stimmell Christopher Thurin Carol Wiley Leonard Yool Elizabeth Stohner Carol Sue Tittman Helen Willenbacher Garr Youngren Mary Stolfa Toiyabe Men’s Golf Club Beverly Williams Robin Zegas Nancy Storck Mitchell Tolep Bradley Williams Alfred Zelinka Nancy Stryker Judy Traister David and Beverly Williams Tony Zertuche Pat Stuart Colleen Trujillo Michael and Jean Williams Deborah Zodkowic Therese McNeely Stuckmann David Turner Ronald J. Stupak Urban ROBERT JAY WEINBERG MEMORIAL Ruth N. Sturkey David Usher DONATIONS HAVE Zita Sulzberger Keke Uzokwe BEEN MADE BY: Nancy Sundstrom Rosaria Valenzano Larry and Rita Susnow Sandi Price & Leslie Van Derhoef Rochelle Ostroff-Weinberg Wynnewood, PA Maxym Sutton Roni VanderBroek William and Norma Lynn Suvak Helen Vanskiver Suzanne and Stan Dorf Donor Nicholas Vassiliou

54 MEMORIAL FUNDS THE MDS FOUNDATION’S WORK HELPS KEEP MEMORIES ALIVE

MEMORIAL DONATIONS HAVE BEEN RECEIVED IN THE NAME OF:

Bill Adams • Angel Andreev • Jean Avola • Charles “Ron” Avret • Vern Lee Baker • Charles Balstad, Sr. • James Raymond Barber • James Barker • Lois Barnett • Zdenek “Sid” Bartos • Ann S. Benedek • Eric Charles Bergman • Ronnie Bernhard • Mia Blumenstock • Frieda Kupferman Brill • Sol Brizer • Eva Brown • Michael Brown • Thomas “Tom” Bruch • Gloria Jean Fournier Bucklin • Daniel J. Burke • David Hammond Burke • Alene Jean Burt • David Thomas Burtc • Jewell Calhoun • Alvaro Cámara • Leonard Camhi • John P. Carroll • Nancy Caruso • Patricia “Patty” Hurley Cherico • Byers Clayton Clark • James Leslie Combs • Edward J. Connolly • Patricia Angela Chiccone Connor• Jeannette Cook • Grady Earl Courtney • Jerry Cowan • Stephen L. Crippen • Thomas E. Criscitelli • Richard L. Cristadoro • Clyde Weber Crooks, Jr.• Barbara Jean Curran • Donald E. Curtin • Sally Anne Cushman • Arthur Cutler • Joseph Davis • Walter Lee Davis, Jr.• Maria DeBonis • Barbara L. Demers • Marion Dotson • Patricia H. Drotleff • Donald A. Dwenger • Joyce Collier Earl • Brenda Effron • Harley T. Emmons, Jr.• Arthur H. “Bushy” Epstein • Joseph E. Ernsteen • Douglas H. Fahrney • William Felder • Roger Joseph Feulner • Bill Fisher • Suzanne Fleischman • Paul Arthur Fleming • Gerald “Jerry” L. Flick • Andreas Fokas • Nancy C. Fox • Ronald J. Foxx • Susan Mary Frank • Herbert G. Frey • Lynn Froistad • Herbert S. Gann • Gerald “Jerry” Francis Genaw • Giri Giridhar • Andrew Paul Glasgow • Tereze Gluck • Robert Goldberg • Kenneth Edward Graham • Laurie Greenbaum • Marc Gross • Vernon Gross • Thelma L. Hale • Lester Handler • Richard Hanson • Harry John Hauck, Jr. • Julianne Heggoy • Martin B. Heiland, Jr. • Martin Heiss • James P. Hellenbrand • John Eric Helmer • Andrew E. Helmich, Sr. • George Michael Herrmann • Brad Hoffman • Kenneth E. Hoffman• Mary Alice Hudzik • Kenneth Edward Hunt• Clifford Ingraham • Patricia Jackson • Karen Jacobs • Robert W. Jarrett , Sr. • Patrick D. Jeffries • Esther Jewler • Mary Catherine Johnson • Gail E. Jolin • Don Kane • Marsha Keefer • Joseph Keough • Christopher Masaaki Kimber • Joe Kirsch • Cindy Klein • Roy T. Kobashigawa • Linda J. Kochevar • Joseph Kotelnicki, Sr. • Robert A. Kramp • Anthony “Tony” Eugene Krauss • Kenneth J. Kunz • Claudette Marie Latsko • Jerry Laufer • Lucille E. Lenzo • Ellis Levy • Joel Levy • Jacqueline List • Thomas Eugene Lovell • John Edwin “Ted” MacNintch • Sharon D. Mahaffey • Bessie Mamolou • Gerald Mandell • Viviano “Larry” Martinez • Kate Maure • Michael J. McCormick • Leah McDermid • Linda L. McGuire • David L. McManis • Marian Grady McNeely • Susan E. Mealy • Wayne R. Meling • Martin S. Meyerson • Michael Micenko • Robert “Bob” Michalec • Louis “Mickey” John Michalski Jr.• Andy Michniewicz • Lee Miller • Michael Mitek • Clifford Ken Miura • R. Howard Mobley, Sr. • Kay L. Moore • Lillian Morris • David H. Morton • David Mucci • Andrew Joseph Mullen • Judith “Judy” Klein Murray • Rosina A. Navagh • Donna Ness • Patricia Mary Davies Newcombe • Isabel O'Connell • Gary O'Connor • Arlene O'Donnell • William Francis O'Donnell, III• Robert Wayne Oglesby • Daniel C. Olmizzi • Judith Olsen • Gloria Ostrowski • John F. Papetti, Sr. • George Joseph Paterni • Susan M. Patrick • Franklin Herbert Pennell, Jr. • Paul E. Pennie • Nick J. Perisin • Joseph A. Perkins, Jr. • Tony Perla, Jr. • Charles I. Peterson • Dorothea Phillips • Ralph Phillips • Kieran Pillion • Livio Pizzinat • Christien Preijers • Armando Pulvera • George Wayne Renniger • Phillip L. Renzetti • Marcia E. Resnik • Steven K. Rhoads • Ajjel Lita Ritchy • Thomas W. Robertson• Abraham (Abe) Rosenthal • Maureen Anne Rouleau • James Michael Ryan • Peter R. Sammarco • Arthur Howard Satten • Allida Emma Sauer • Cathy Schmidt • Stanley Scholsohn • Walter H. Schoolcraft • Mildred Marie Schuette • Brian Schwartz • Merle Schwartz • Stephen Scola • William John Seelie • Irving Seidman • Kathleen Seifferth • Sol Iris Sepulveda • Dr. Eliseo B. Serina • Donald M. Shachat • Marlene Shervey • William Shoaf • Thomas H. Shuey• Roy Shumard • Joyce Simoes • Ruthanne Simons • Donald R. Smith • Jean Marie Sode • Ronald Solberg • Leon A. Soltysiak, Jr. • Michael Sortino • Jerry E. Spann • Eddie Neil Speer • Raymond P. Stohner • Patricia Davey Struck • David Sundstrom • Lillian “Lilly” M. Campo Susienka • H. Franklin Taylor, III • Remo Joseph Tersolo • Joyce “Jo” Thompson • Jeannette Toth • Dennis Alvin Totty • Jack G. Turner • Dawn A. Van Tuyl • Carol A. Usher • Paul Valenzano• Ron Vanskiver• Calvin A. Vobroucek• Rita B. Voit• John Roy Wagnes• Ives J. Wahrman• Esther Keleman Walsh • Jim L. Warren • Rebecca “Becky” D. Wentworth • Gertrude “Trudy” Wetterling • Gwendolyn Whitehead • Marc L. Wiener • Dillon Claude Williams • Robert “Bob” Arthur Williams, II • Neal Wingfield • Richard Winterhalter • Aaron Wishnevsky • Bernard Wohlstetter • Sheila Carol Wolfson • Janis Wyman • Andrew Zaloga • Jennifer Zighelboim

Honor or memorialize your loved one at: www.mds.foundation.org/donate or contact us at 800-MDS-0839 (within US), 609-298-1035 (Outside US).

55 LIVING ENDOWMENTS

LIVING ENDOWMENT DONATIONS HAVE BEEN MADE IN HONOR OF: Wyn Aubrey-Child Ashley Cámara Bill Williamson Submitted by: Donald Child Submitted by: Submitted by: Marilyn Williamson Herman B. Lustigman Bryan Davis Cherie Willerscheidt Charitable Foundation Submitted by: Submitted by: Jeanne Mandel Joann Davis, Trevor Davis James Gisonde Julia McGuire Submitted by: Kathryn Gisonde Barbara Unwin Submitted by: Marguerite McKenna Submitted by: Jill Whitney William H. Sargent Wayne and Lorraine Zerfas Submitted by: Jan Brown Submitted by: Katharine Sargent Anandiben Shah Jody Senna Syd Schneider Submitted by: Janet Kelske Submitted by: Sher Pollard Submitted by: Joan Karlin Carolyn Wing Tanya and Albert Lampert Submitted by: Beverly Taylor Submitted by: Suzanne Brown Mona Kelly George P. Ratte Judith Knapp Submitted by: Submitted by: Frederick Jaffke Submitted by: James Snyder Ultimate Software Group, Inc. Brian Scott Anderson Dorothy Acalin Frieda "Fritzi" Submitted by: Submitted by: Andrea Alexander Submitted by: Ray and Wendy Tarantola Stan and Suzanne Dorf Arthur Jacobson Richard Clark Submitted by: Amy Clark Opal Belisle Theresa Tintor Submitted by: Submitted by: Rhonda Chapman Joe Senna, Jr. Randall and Susan Peterson Toni Spena, Ryan Goldstein Submitted by: DeRon Senna Jason Curtis Rob Allred William Painter Submitted by: Submitted by: Submitted by: Charlotte and George Lucas Matthew and Alison French Laura Wilson, Carole Flores

DThe Myelodysplasticid Yo Syndromesu K (MDS)no Foundation,w? Inc. was established by an international group of physicians and researchers to provide an ongoing exchange of information relating to MDS. Until the Foundation was set up, no formal working group had been devoted to MDS. Since its inception, we have conducted 15 international symposia in Austria, England, the United States (Chicago, Washington, DC), Spain (Barcelona, Valencia), Czech Republic, Sweden, France, Japan, Italy, Greece, Scotland, Germany, and Denmark. The 16th International Symposium will be held in Toronto, Canada on May 5-8, 2021. A major MDS Foundation effort is our international information network. This network provides patients with referrals to Centers of Excellence, contact names for available clinical trials, sharing of new research and treatment options between physicians, and extension of educational support to physicians, nurses, pharmacists and patients. In response to the needs expressed by patients, families, and healthcare professionals, we have established patient advocacy groups, research funding, and professional educational initiatives. The MDS Foundation is a publicly supported organization, exempt from federal income tax under section 501(C)(3) of the IRS code. Learn more about The Myelodysplastic Syndromes Foundation, Inc. and find additional resources here: the myelodysplastic syndromes foundation, inc. www.mds-foundation.org

56 A esingl source for access support

At Celgene Patient Support®, we care about making sure you get the help you need to start your prescribed Celgene medicine. Our Specialists are ready to help you and your family with: • Understanding your insurance plan • Learning about nancial assistance • Obtaining information about organizations that may assist you with travel costs to and from your doctor’s of ce

Enrollment in Celgene Patient Support® is simple—choose the option that is best for you.

Enroll online at www.celgenepatientsupport.com

Call us at 1-800-931-8691, Monday – Thursday, 8 AM – 7 PM ET, and Friday, 8 AM – 6 PM ET (translation services available)

E-mail us at [email protected]

Celgene Patient Support® is a registered trademark of Celgene Corporation. Leah © 2018 Celgene Corporation 08/18 US-CELG170308 Celgene Patient Support® Specialist

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ARE BLOOD TRANSFUSIONS HOLDING YOU BACK? If you’ve been diagnosed with myelodysplastic syndromes (MDS) with anemia, the phase 3 COMMANDS Trial is a clinical research study investigating a potential treatment option that may help reduce the number of blood cell transfusions you need. To learn more, talk to your doctor and visit ClinicalTrialCOMMANDS.com.

ACE-536-MDS-002_COMMANDS_V1_26FEB2019_US_ENG

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NOW ENROLLING PANTHER TRIAL PEVONEDISTAT-3001(NCT 03268954): Designed to evaluate the safety and efficacy of pevonedistat plus azacitidine versus single-agent azacitidine as a first-line treatment for patients with higher-risk myelodysplastic syndromes (HR MDS), chronic myelomonocytic leukemia (CMML), or low-blast acute myelogenous leukemia (AML)

pevonedistat + STRATIFICATION azacitidine • IPSS-R risk category Global phase 3 for HR MDS/CMML: clinical study Randomized 1:1 – Intermediate (N=450) – High – Very high azacitidine • Low-blast AML

Primary endpoint: Event-free survival (EFS) Key secondary endpoint: Overall survival (OS) Not a complete list of endpoints.

Enrolling countries Australia, Belgium, Brazil, Canada, Czech Republic, France, Germany, Greece, Israel, Italy, Japan, Mexico, Poland, Russian Federation, South Korea, Spain, Turkey, UK, USA For more information, including all inclusion and exclusion criteria 1-844-ONC-TKDA (1-844-662-8532) (US callers) +1-510-740-1273 (ex-US callers) www.clinicaltrials.gov or www.takedaoncology.com

For information on enrolling a patient, please contact [email protected].

Pevonedistat is an investigational drug. Efficacy and safety have not been established.

All trademarks are the property of their respective owners. ©2019 Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. All rights reserved. 2/19 MAT-USO-NON-19-00043

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