Myeloproliferative Neoplasms Myelofibrosis, Polycythemia Vera and Essential Thrombocythemia
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Updates in Mastocytosis
Updates in Mastocytosis Tryptase PD-L1 Tracy I. George, M.D. Professor of Pathology 1 Disclosure: Tracy George, M.D. Research Support / Grants None Stock/Equity (any amount) None Consulting Blueprint Medicines Novartis Employment ARUP Laboratories Speakers Bureau / Honoraria None Other None Outline • Classification • Advanced mastocytosis • A case report • Clinical trials • Other potential therapies Outline • Classification • Advanced mastocytosis • A case report • Clinical trials • Other potential therapies Mastocytosis symposium and consensus meeting on classification and diagnostic criteria for mastocytosis Boston, October 25-28, 2012 2008 WHO Classification Scheme for Myeloid Neoplasms Acute Myeloid Leukemia Chronic Myelomonocytic Leukemia Atypical Chronic Myeloid Leukemia Juvenile Myelomonocytic Leukemia Myelodysplastic Syndromes MDS/MPN, unclassifiable Chronic Myelogenous Leukemia MDS/MPN Polycythemia Vera Essential Thrombocythemia Primary Myelofibrosis Myeloproliferative Neoplasms Chronic Neutrophilic Leukemia Chronic Eosinophilic Leukemia, NOS Hypereosinophilic Syndrome Mast Cell Disease MPNs, unclassifiable Myeloid or lymphoid neoplasms Myeloid neoplasms associated with PDGFRA rearrangement associated with eosinophilia and Myeloid neoplasms associated with PDGFRB abnormalities of PDGFRA, rearrangement PDGFRB, or FGFR1 Myeloid neoplasms associated with FGFR1 rearrangement (EMS) 2017 WHO Classification Scheme for Myeloid Neoplasms Chronic Myelomonocytic Leukemia Acute Myeloid Leukemia Atypical Chronic Myeloid Leukemia Juvenile Myelomonocytic -
Mutation Analysis in Myeloproliferative Neoplasms AHS - M2101
Corporate Medical Policy Mutation Analysis in Myeloproliferative Neoplasms AHS - M2101 File Name: mutation_analysis_in_myeloproliferative_neoplasms Origination: 1/1/2019 Last CAP review: 8/2021 Next CAP review: 8/2022 Last Review: 8/2021 Description of Procedure or Service Myeloproliferative neoplasms (MPN) are a heterogeneous group of clonal disorders characterized by overproduction of one or more differentiated myeloid lineages (Grinfeld, Nangalia, & Green, 2017). These include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The majority of MPN result from somatic mutations in the 3 driver genes, JAK2, CALR, and MPL, which represent major diagnostic criteria in combination with hematologic and morphological abnormalities (Rumi & Cazzola, 2017). Related Policies: BCR-ABL 1 Testing for Chronic Myeloid Leukemia AHS-M2027 ***Note: This Medical Policy is complex and technical. For questions concerning the technical language and/or specific clinical indications for its use, please consult your physician. Policy BCBSNC will provide coverage for mutation analysis in myeloproliferative neoplasms when it is determined to be medically necessary because the medical criteria and guidelines shown below are met. Benefits Application This medical policy relates only to the services or supplies described herein. Please refer to the Member's Benefit Booklet for availability of benefits. Member's benefits may vary according to benefit design; therefore member benefit language should be reviewed before applying the terms of this medical policy. When Mutation Analysis in Myeloproliferative Neoplasms is covered 1. JAK2, CALR or MPL mutation testing is considered medically necessary for the diagnosis of patients presenting with clinical, laboratory, or pathological findings suggesting classic forms of myeloproliferative neoplasms (MPN), that is, polycythemia vera (PV), essential thrombocythemia (ET), or primary myelofibrosis (PMF) when ordered by a hematology and/or oncology specialist in the following situations: A. -
A Comparative Study of Murine Mast Cell Progenitors
Virginia Commonwealth University VCU Scholars Compass Theses and Dissertations Graduate School 2001 A Comparative Study of Murine Mast Cell Progenitors Shirley K. DeSimone Follow this and additional works at: https://scholarscompass.vcu.edu/etd Part of the Other Medicine and Health Sciences Commons © The Author Downloaded from https://scholarscompass.vcu.edu/etd/4529 This Dissertation is brought to you for free and open access by the Graduate School at VCU Scholars Compass. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of VCU Scholars Compass. For more information, please contact [email protected]. Virginia Commonwealth University School of Medicine This is to certifythat the dissertation prepared by Shirley K. DeSimone entitled "A Comparative Study of Murine Mast Cell Progenitors" has been approved by her committee as satisfactory completion of the disse1tation requirement for the degree of Doctor of Philosophy. Francine M. Marciano-Cabral, Ph.D., School of Medicine Jack L. Haar, Ph.D., Dean, School of Graduate Studies A Comparative Study of Murine Mast Cell Progenitors A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University By Shirley K. DeSimone Director: Thomas F. Huff, Ph.D. Professor, Microbiology and Immunology Virginia Commonwealth University Richmond, Virginia May, 2001 11 Acknowledgments I wish to thank my advisor, Dr. Thomas F. Hufffor his insight, guidance, and patience. also which to acknowledge the invaluable, unwavering, and loving support of my husband, friend and companion, Dr. John A. DeSimone. Thanks are also due to the consistently helpful graduate students of Dr. -
An Overview of the Role of Hdacs in Cancer Immunotherapy
International Journal of Molecular Sciences Review Immunoepigenetics Combination Therapies: An Overview of the Role of HDACs in Cancer Immunotherapy Debarati Banik, Sara Moufarrij and Alejandro Villagra * Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, 800 22nd St NW, Suite 8880, Washington, DC 20052, USA; [email protected] (D.B.); [email protected] (S.M.) * Correspondence: [email protected]; Tel.: +(202)-994-9547 Received: 22 March 2019; Accepted: 28 April 2019; Published: 7 May 2019 Abstract: Long-standing efforts to identify the multifaceted roles of histone deacetylase inhibitors (HDACis) have positioned these agents as promising drug candidates in combatting cancer, autoimmune, neurodegenerative, and infectious diseases. The same has also encouraged the evaluation of multiple HDACi candidates in preclinical studies in cancer and other diseases as well as the FDA-approval towards clinical use for specific agents. In this review, we have discussed how the efficacy of immunotherapy can be leveraged by combining it with HDACis. We have also included a brief overview of the classification of HDACis as well as their various roles in physiological and pathophysiological scenarios to target key cellular processes promoting the initiation, establishment, and progression of cancer. Given the critical role of the tumor microenvironment (TME) towards the outcome of anticancer therapies, we have also discussed the effect of HDACis on different components of the TME. We then have gradually progressed into examples of specific pan-HDACis, class I HDACi, and selective HDACis that either have been incorporated into clinical trials or show promising preclinical effects for future consideration. -
Treatment Approaches to Polycythemia Vera and Myelofibrosis
REVIEW ARTICLE Rev Hematol Mex. 2016 Apr;17(2):129-138. Treatment approaches to polycythemia vera and myelofibrosis. Palmer J, Mesa R Abstract Myeloproliferative neoplasms consist of a diverse group of disorders. Over the last 10 years, with better understanding of pathophysiology of these disorders, there are many more treatment options available to patients with these diseases. Further, improved understanding of the underlying genetic landscape has led to improved prognostication which helps identify appropriate therapeutic options. For polycythe- mia vera, initial therapy generally includes aspirin and phlebotomy. However, in patients who do not achieve an appropriate response to phlebotomy, hydroxyurea or ruxolitinib can be considered. In patients who have myelofibrosis, therapy is determined by symptom burden. In patients who have significant constitutional symptoms, a JAK inhibitor, such as ruxolitinib is an appropriate choice. There are many novel therapies under investigation for patients with myelofibrosis, including anti-fibrotic agents, novel JAK inhibitors, telomerase inhibitors and allogeneic stem cell transplant. KEYWORDS: polycythemia vera; myelofibrosis; treatment Rev Hematol Mex. 2016 abr;17(2):129-138. Enfoques terapéuticos de policitemia vera y mielofibrosis Palmer J, Mesa R Resumen Las neoplasias mieloproliferativas consisten en un diverso grupo de enfermedades. En los últimos 10 años, con mejor comprensión de estas enfermedades, hay mas opciones de tratamiento disponibles para los pacientes que las padecen. Además, el mejor entendimiento del pano- rama genético detrás de estas enfermedades ha contribuido a mejorar el pronóstico, lo que ayuda a identificar las opciones terapéuticas Mayo Clinic, Phoenix AZ, USA. adecuadas. El tratamiento inicial de la policitemia vera generalmente incluye aspirina y flebotomía. -
Vorinostat—An Overview Aditya Kumar Bubna
E-IJD RESIDENTS' PAGE Vorinostat—An Overview Aditya Kumar Bubna Abstract From the Consultant Vorinostat is a new drug used in the management of cutaneous T cell lymphoma when the Dermatologist, Kedar Hospital, disease persists, gets worse or comes back during or after treatment with other medicines. It is Chennai, Tamil Nadu, India an efficacious and well tolerated drug and has been considered a novel drug in the treatment of this condition. Currently apart from cutaneous T cell lymphoma the role of Vorinostat for Address for correspondence: other types of cancers is being investigated both as mono-therapy and combination therapy. Dr. Aditya Kumar Bubna, Kedar Hospital, Mugalivakkam Key Words: Cutaneous T cell lymphoma, histone deacytelase inhibitor, Vorinostat Main Road, Porur, Chennai - 600 125, Tamil Nadu, India. E-mail: [email protected] What was known? • Vorinostat is a histone deacetylase inhibitor. • It is an FDA approved drug for the treatment of cutaneous T cell lymphoma. Introduction of Vorinostat is approximately 9. Vorinostat is slightly Vorinostat is a histone deacetylase (HDAC) inhibitor, soluble in water, alcohol, isopropanol and acetone and is structurally belonging to the hydroxymate group. Other completely soluble in dimethyl sulfoxide. drugs in this group include Givinostat, Abexinostat, Mechanism of action Panobinostat, Belinostat and Trichostatin A. These Vorinostat is a broad inhibitor of HDAC activity and inhibits are an emergency class of drugs with potential anti- class I and class II HDAC enzymes.[2,3] However, Vorinostat neoplastic activity. These drugs were developed with the does not inhibit HDACs belonging to class III. Based on realization that apart from genetic mutation, alteration crystallographic studies, it has been seen that Vorinostat of HDAC enzymes affected the phenotypic and genotypic binds to the zinc atom of the catalytic site of the HDAC expression in cells, which in turn lead to disturbed enzyme with the phenyl ring of Vorinostat projecting out of homeostasis and neoplastic growth. -
Acute Myeloid Leukemia Evolving from JAK 2-Positive Primary Myelofibrosis and Concomitant CD5-Negative Mantle Cell
Hindawi Publishing Corporation Case Reports in Hematology Volume 2012, Article ID 875039, 6 pages doi:10.1155/2012/875039 Case Report Acute Myeloid Leukemia Evolving from JAK 2-Positive Primary Myelofibrosis and Concomitant CD5-Negative Mantle Cell Lymphoma: A Case Report and Review of the Literature Diana O. Treaba,1 Salwa Khedr,1 Shamlal Mangray,1 Cynthia Jackson,1 Jorge J. Castillo,2 and Eric S. Winer2 1 Department of Pathology and Laboratory Medicine, Rhode Island Hospital, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA 2 Division of Hematology/Oncology, The Miriam Hospital, The Warren Alpert Medical School, Brown University, Providence, RI 02904, USA Correspondence should be addressed to Diana O. Treaba, [email protected] Received 2 April 2012; Accepted 21 June 2012 Academic Editors: E. Arellano-Rodrigo, G. Damaj, and M. Gentile Copyright © 2012 Diana O. Treaba et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Primary myelofibrosis (formerly known as chronic idiopathic myelofibrosis), has the lowest incidence amongst the chronic myeloproliferative neoplasms and is characterized by a rather short median survival and a risk of progression to acute myeloid leukemia (AML) noted in a small subset of the cases, usually as a terminal event. As observed with other chronic myeloproliferative neoplasms, the bone marrow biopsy may harbor small lymphoid aggregates, often assumed reactive in nature. In our paper, we present a 70-year-old Caucasian male who was diagnosed with primary myelofibrosis, and after 8 years of followup and therapy developed an AML. -
3Rd Year BLOOD and IMMUNOLOGY II Study Guide
BLOOD AND IMMUNOLOGY II MODULE STUDY GUIDE 3RD YEAR MBBS Contents Vision and Mission of KGMC ................................................................................................................................................................................................ Khyber Medical University: Vision ....................................................................................................................................................................................... Khyber Girls Medical College: Vision ................................................................................................................................................................................... Khyber Girls Medical College: Mission ............................................................................................................................................................................... Curriculum Committee KGMC .............................................................................................................................................................................................. Module committee ............................................................................................................................................................................................................... Outcomes of the curriculum: .............................................................................................................................................................................................. -
Mutations and Prognosis in Primary Myelofibrosis
Leukemia (2013) 27, 1861–1869 & 2013 Macmillan Publishers Limited All rights reserved 0887-6924/13 www.nature.com/leu ORIGINAL ARTICLE Mutations and prognosis in primary myelofibrosis AM Vannucchi1, TL Lasho2, P Guglielmelli1, F Biamonte1, A Pardanani2, A Pereira3, C Finke2, J Score4, N Gangat2, C Mannarelli1, RP Ketterling5, G Rotunno1, RA Knudson5, MC Susini1, RR Laborde5, A Spolverini1, A Pancrazzi1, L Pieri1, R Manfredini6, E Tagliafico7, R Zini6, A Jones4, K Zoi8, A Reiter9, A Duncombe10, D Pietra11, E Rumi11, F Cervantes12, G Barosi13, M Cazzola11, NCP Cross4 and A Tefferi2 Patient outcome in primary myelofibrosis (PMF) is significantly influenced by karyotype. We studied 879 PMF patients to determine the individual and combinatorial prognostic relevance of somatic mutations. Analysis was performed in 483 European patients and the seminal observations were validated in 396 Mayo Clinic patients. Samples from the European cohort, collected at time of diagnosis, were analyzed for mutations in ASXL1, SRSF2, EZH2, TET2, DNMT3A, CBL, IDH1, IDH2, MPL and JAK2. Of these, ASXL1, SRSF2 and EZH2 mutations inter-independently predicted shortened survival. However, only ASXL1 mutations (HR: 2.02; Po0.001) remained significant in the context of the International Prognostic Scoring System (IPSS). These observations were validated in the Mayo Clinic cohort where mutation and survival analyses were performed from time of referral. ASXL1, SRSF2 and EZH2 mutations were independently associated with poor survival, but only ASXL1 mutations held their prognostic relevance (HR: 1.4; P ¼ 0.04) independent of the Dynamic IPSS (DIPSS)-plus model, which incorporates cytogenetic risk. In the European cohort, leukemia-free survival was negatively affected by IDH1/2, SRSF2 and ASXL1 mutations and in the Mayo cohort by IDH1 and SRSF2 mutations. -
Polycythemia Vera Cancer Cluster Investigation in Northeast PA
Polycythemia Vera Cancer Cluster Investigation in Northeast PA Environmental toxic substances found historically in the PV cluster area and their potential for inducing DNA damage Investigating PV What is PV? PV is one of the diseases known as MPNs (myeloproliferative neoplasms). MPNs are a group of blood cancers where the bone marrow makes too many blood cells. Other illnesses included in this group of diseases are essential thrombocytosis (ET) and primary myelofibrosis (PMF). How does the body make blood cells? The body’s bone marrow contains billions of cells, but only a very tiny group plays a key role in forming blood cells (hematopoiesis). This group is composed of hematopoietic stem cells, which provide the body with a constant supply of all types of blood cells throughout life. What causes PV? The cause of PV is unknown. Scientists do know that a gene mutation (called the JAK2V617F mutation or “JAK2”) occurs in about 97% of PV cases. A gene mutation is a permanent change in the DNA sequence that makes up a gene inside the cells of a person’s body. The causes of the JAK2 mutation are also unknown. What is the history of the ATSDR PV investigation? • In 2005, local physicians and community members in Carbon, Luzerne, and Schuylkill counties raised concerns about the diagnosis of four cases of PV on the same rural road in the area where the three counties come together. • Residents also raised concerns about possible historical and current exposures to hazardous chemicals from various locations in the tri-county area. • The Pennsylvania Department of Health asked ATSDR for help investigating the cases and pattern of PV in this area of northeast Pennsylvania. -
Myelofibrosis (MF)
Myelofibrosis (MF) A Guide for Patients Introduction Being diagnosed with myelofibrosis (MF) can be a shock, particularly when you may have never heard of it. If you have questions about MF – what causes it, who it affects, how it affects your body, what symptoms to expect and likely treatments – this booklet covers the basics for you. You will also find useful advice Haematologist at University about how to get the best from Hospital of Wales, Cardiff. We your haematologist, plus practical are also grateful to Chris Rogers, advice on how to help important patient reviewer, for his valuable people in your life understand contribution. The rewrite was put such a rare condition. For together by Lisa Lovelidge and more information talk to your peer reviewed by Professor Claire haematologist or clinical nurse Harrison. This booklet has since specialist. been updated by our Patient Information Writer Isabelle Leach This booklet originally written and peer reviewed by Dr Sebastian by Professor Claire Harrison, Francis. We also appreciate Consultant Haematologist Norman Childs and Amy Cross for at Guy’s and St Thomas’ their input as patient reviewers NHS Foundation Trust, and as well as Samantha Robertson subsequently revised by Dr whose husband had MF. Steve Knapper, Consultant If you would like any information on the sources used for this booklet, please email [email protected] for a list of references. Version 4 Printed: 10/2020 2 www.leukaemiacare.org.uk Review date: 10/2022 In this booklet Introduction 2 In this booklet 3 About Leukaemia Care 4 What is myelofibrosis? 6 What are the signs and symptoms of MF? 9 How is MF diagnosed? 10 What is the treatment for MF? 12 Living with MF 26 Talking about MF 28 Glossary 31 Useful contacts and further support 39 Helpline freephone 08088 010 444 3 About Leukaemia Care Leukaemia Care is a national charity dedicated to ensuring that people affected by blood cancer have access to the right information, advice and support. -
Essential Thrombocythemia Polycythemia Vera
n ESSENTIAL THROMBOCYTHEMIA n POLYCYTHEMIA VERA n MYELOFIBROSIS ADVOCACY & EDUCATION mpnadvocacy.com INTERNATIONAL mpnadvocacy.com MPN Advocacy & Education International MPN Advocacy and Education International provides educational programs, materials, Ann Brazeau, CEO and resources for patients, caregivers, physicians, and entire healthcare teams to improve their understanding of myelofibrosis, polycythemia vera, and essential thrombocythemia. They are dedicated to making a difference in the lives of those affected by MPNs and strive to grow awareness and advocate on behalf of the MPN community. Kathleen Michael Vice President Advocacy Our advocacy efforts extend beyond responding to the unmet needs of the MPN Community. We identify concerns in a meaningful and productive way and create initiatives that impact quality care, treatment access, new drug development and represent MPN patients and organizations who are unable to address the issues surrounding a blood cancer diagnosis. Women and MPN and Pediatric and Young Adult initiatives have expanded Dr. Ruben Mesa, MD, Scientific Advisor the interest and exploration into the unmet needs of these UT Health San Antonio patient groups. Cancer Center Education MPN Education programs are held across the country and internationally each year. Our speakers are MPN specialists who share updated information on research, clinical trials, treatment options, and comprehensive quality of life direction. Dr. Ruben Mesa, MD, is our scientific advisor and frequent speaker at our educational programs. VIEW EVENTS Please visit our website at www.mpnadvocacy.com for more information on events, advocacy initiatives, patient support groups in your area and numerous resources. PAGE ONE What are Myeloproliferative Neoplasms (MPN)? Myelo – prefix referring to bone marrow Proliferative – increasing the numbers of cells Neoplasm – any new and abnormal growth, where cell multiplication is uncontrolled and progressive.