What Is Minimal Residual Disease (MRD)?

Total Page:16

File Type:pdf, Size:1020Kb

What Is Minimal Residual Disease (MRD)? What is Minimal Residual Disease (MRD)? After treatment, there may be a small number of cancer cells that remain in the body. This is referred to minimal residual disease (MRD). The remaining number of cells may be so small that they do not cause any physical signs or symptoms. They usually go undetected through traditional methods, such as viewing cells under a microscope or by checking for abnormal serum proteins in the blood. If a patient receives an MRD positive test result, it means that residual (remaining) cancer cells have been detected. A negative result means that no residual disease is detected. What role does Minimal Residual Disease (MRD) assessment play in-patient care? Any remaining cancer cells can become active and begin to multiply, causing the patient to relapse. MRD assessment helps indicate if the treatment was not completely effective. Minimal residual disease might be present after treatment because not all the cancer cells responded to therapy. Is a negative MRD result a positive sign? A positive test result for MRD, known as “MRD positivity”, indicates that residual cancer cells are present in the body after treatment. When a patient tests negative for minimal residual disease, known as “MRD negativity”, there are no remaining cancer cells. Being “MRD negative” is an encouraging outcome for a patient with blood cancer. MRD negativity means that even with advanced, sensitive tests, no cancer cells were detected. According to studies, MRD negativity is associated with longer remissions and potentially longer rates of survival for certain blood cancers. 1 How does MRD testing affect my treatment? Testing for MRD can help our treatment team distinguish between patients who need additional or different treatment from those who do not. This knowledge can also guide treatment decisions and improve patient outcomes. Minimal residual disease testing helps: ● Show how well cancer has responded to treatment ● Confirm and monitor remissions ● Detect cancer recurrence sooner than other tests ● Identify a higher risk of relapse in patients ● Identify the need to restart treatment ● Identify patients who are candidates for procedures such as stem cell transplantation or combination therapy. When would doctors test for MRD? Testing for MRD in patients is dependent on varying factors specific to the patient’s disease. Patients may be tested: ● After bone marrow transplantation. ● After the last cycle of a planned combination therapy. ● During treatment. ● After one year of maintenance therapy. ● To confirm the depth of remission. ● At regular intervals, once treatment is completed. ● At other specific times. 2 What are the techniques used to detect MRD? MRD testing uses highly sensitive methods such as flow cytometry, polymerase chain reaction (PCR), and next-generation sequencing (NGS). Each of these tests uses bone marrow cell samples taken through aspiration, or peripheral blood cells taken through a vein. 3 MRD Testing in Specific Blood Cancers The type of MRD testing used depends on the type of blood cancer. Acute Lymphoblastic Leukaemia (ALL) For patients with ALL, MRD is detected through flow cytometry, PCR, and NGS. ● When treating paediatric and adult ALL, MRD is part of routine testing. ● MRD can predict the effectiveness of a specific treatment after the induction phase of ALL treatment. ● MRD can identify patients who are at higher risk of relapse. This allows administration of earlier or alternative therapies. MRD can determine patients who may benefit from a bone marrow transplantation. Chronic Lymphocytic Leukaemia (CLL) For patients with CLL, MRD is detected by flow cytometry and PCR. ● MRD negativity in patients after CLL therapy may have better treatment outcomes. ● MRD positivity in patients after treatment are potential candidates for treatment intensification, consolidation and maintenance strategies. Chronic Myeloid Leukaemia (CML) For patients with CML, MRD is detected through PCR. ● PCR can detect the Philadelphia (Ph) chromosome found in 95% of CML patients. ● PCR can detect one Ph+ CML cell in one million healthy cells. ● MRD monitoring helps predict resistance to treatment and guide the course of the patient’s treatment. 4 Lymphoma For patients with lymphoma, MRD is detected through flow cytometry and PCR. ● MRD testing can detect patients who are at risk of relapsing, allowing them to receive additional treatment. ● MRD testing is used in follicular, mantle cell and diffuse large B-cell lymphoma (DLBCL). ● Patients treated for mantle cell lymphoma and achieve MRD negativity have shown to have prolonged remissions. ● Studies have demonstrated that DLBCL patients who achieved remission and MRD negativity after treatment were more likely to remain in remission compared to patients who had achieved remission with MRD positivity. Myeloma For patients with myeloma, MRD testing uses flow cytometry, NGS, and imaging tests. ● PET-CT scans combined with other tests help doctors find disease present outside the bone marrow. ● Patients who achieve MRD negativity after treatment live longer without disease progression, according to several studies. Disclaimer: The information on the Centre For Clinical Haematology website is intended for educational use. It should not be considered or used as a substitute for medical advice, diagnosis or treatment from a qualified health professional. 5 .
Recommended publications
  • Minimal Residual Disease Detection in Childhood Precursor–B-Cell Acute Lymphoblastic Leukemia: Relation to Other Risk Factors
    Leukemia (2003) 17, 1566–1572 & 2003 Nature Publishing Group All rights reserved 0887-6924/03 $25.00 www.nature.com/leu Minimal residual disease detection in childhood precursor–B-cell acute lymphoblastic leukemia: relation to other risk factors. A Children’s Oncology Group study MJ Borowitz1, DJ Pullen2, JJ Shuster3,4, D Viswanatha5, K Montgomery6, CL Willman5 and B Camitta7 1Johns Hopkins Medical Institutions, USA; 2University of Mississippi, USA; 3University of Florida, Gainesville FL, USA; 4Children’s Oncology Group, Arcadia, CA, USA; 5University of New Mexico, USA; 6Genzyme Genetics, Santa Fe, NM; and 7Milwaukee Childrens Hospital, USA Minimal residual disease (MRD) can be detected in the marrows prognostic significance at several time points. MRD levels at the of children undergoing chemotherapy either by flow cytometry end of induction are highly prognostic. Since intensification of or polymerase chain reaction. In this study, we used four-color therapy after successful induction can improve the outcome of flow cytometry to detect MRD in 1016 children undergoing 33 therapy on Children’s Oncology Group therapeutic protocols many patients with adverse prognostic features, it is possible for precursor–B-cell ALL. Compliance was excellent, with that a similar approach might benefit patients with MRD. For follow-up samples received at the end of induction on nearly these reasons, we have chosen to focus our MRD studies on 95% of cases; sensitivity of detection at this time point was at end-of-induction therapy. least 1/10,000 in more than 90% of cases. Overall, 28.6% of Although MRD and other measures of early response to patients had detectable MRD at the end of induction.
    [Show full text]
  • Effect of the Philadelphia Chromosome on Minimal Residual Disease In
    Leukemia (1997) 11, 1497–1500 1997 Stockton Press All rights reserved 0887-6924/97$12.00 Effect of the Philadelphia chromosome on minimal residual disease in acute lymphoblastic leukemia MJ Brisco1, PJ Sykes1, G Dolman1, S-H Neoh1, E Hughes1, L-M Peng2, G Tauro3, H Ekert3, I Toogood4, K Bradstock5 and AA Morley1 1Department of Haematology, Flinders Medical Centre, Bedford Park, South Australia; 2Department of Laboratory Medicine, School of Medicine, West China University of Medical Sciences, Chengdu, People’s Republic of China; 3Department of Haematology, Royal Childrens Hospital, Parkville, Victoria; 4Department of Haematology/Oncology, Womens and Childrens Hospital, North Adelaide, South Australia; and 5Department of Haematology, Westmead Hospital, Westmead, NSW, Australia The Philadelphia translocation is associated with a poor prog- number of leukemic cells remaining at the end of induction nosis in adults and children with acute lymphoblastic leukemia, provides a good approximation of the degree of drug resist- even though the majority of patients achieve remission. To test ance in vivo. the hypothesis that the translocation leads to drug resistance 6–10 in vivo, we studied 61 children and 20 adults with acute lym- Since the initial reports, a number of groups have phoblastic leukemia and used the level of minimal residual dis- developed sensitive methods to quantify minimal residual dis- ease at the end of induction as the measure of drug resistance ease (MRD) by use of the polymerase chain reaction (PCR). in vivo. In children
    [Show full text]
  • REVIEW Clinical Relevance of Minimal Residual Disease Monitoring in Non
    Leukemia (1999) 13, 1691–1695 1999 Stockton Press All rights reserved 0887-6924/99 $15.00 http://www.stockton-press.co.uk/leu REVIEW Clinical relevance of minimal residual disease monitoring in non-Hodgkin’s lymphomas: a critical reappraisal of molecular strategies P Corradini1, M Ladetto2, A Pileri2 and C Tarella2 1Bone Marrow Transplantation Unit, Istituto Scientifico HS Raffaele, Milan; and 2Divisione Universitaria di Ematologia–Azienda Ospedaliera S Giovanni Battista, Turin, Italy Although current treatments can induce clinical complete neoplasms. In the NHL setting, several studies have been pub- remissions in the vast majority of patients with indolent lym- lished on the prognostic significance of minimal residual dis- phoma, most of them actually relapse, because of the persist- ence of residual tumor cells which are undetectable using con- ease (MRD) detection. Most of these studies focus on indolent ventional diagnostic procedures. Polymerase chain reaction lymphomas: small lymphocytic lymphoma/chronic lympho- (PCR)-based methods are increasingly used for minimal cytic leukemia (SLL/CLL),17,18 follicular (FCL)19–21 and mantle residual disease detection (MRD), and provide useful prognos- cell lymphomas (MCL).20,22 This is mostly because these tic information. In this review, current approaches for MRD tumors, unlike more aggressive NHL histotypes, are dissemi- detection in indolent lymphomas are summarized. In addition, nated disorders with frequent microscopic or submicroscopic the prognostic aspects of molecular monitoring after transplan- tation procedures are discussed. The experience accumulated bone marrow (BM) and peripheral blood (PB) involvement, over the past decade shows that PCR analysis has a prognostic and thus they represent ideal targets for MRD evaluation with impact in several therapeutic programs including conventional PCR-based assays.23,24 and high-dose regimens.
    [Show full text]
  • How Close Are We to Incorporating Measurable Residual Disease Into
    REVIEW ARTICLE How close are we to incorporating Ferrata Storti Foundation measurable residual disease into clinical practice for acute myeloid leukemia? Nicholas J. Short and Farhad Ravandi Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Haematologica 2019 ABSTRACT Volume 104(8):1532-1541 ssessment of measurable residual disease, also called “minimal resid - ual disease,” in patients with acute myeloid leukemia in morpholog - Aical remission provides powerful prognostic information and comple - ments pretreatment factors such as cytogenetics and genomic alterations. Based on data that low levels of persistent or recurrent residual leukemia are consistently associated with an increased risk of relapse and worse long- term outcomes, its routine assessment has been recommended by some experts and consensus guidelines. In addition to providing important prog - nostic information, the detection of measurable residual disease may also theoretically help to determine the optimal post-remission strategy for an individual patient. However, the full therapeutic implications of measurable residual disease are uncertain and thus controversy exists as to whether it should be routinely incorporated into clinical practice. While some evidence supports the use of allogeneic stem cell transplantation or hypomethylating agents for some subgroups of patients in morphological remission but with detectable residual leukemia, the appropriate use of this information in mak - ing clinical decisions remains largely speculative at present. To resolve this pressing clinical issue, several ongoing studies are evaluating measurable Correspondence: residual disease-directed treatments in acute myeloid leukemia and may FARHAD RAVANDI lead to new, effective strategies for patients in these circumstances. This [email protected] review examines the common technologies used in clinical practice and in the research setting to detect residual leukemia, the major clinical studies Received: February 8, 2019.
    [Show full text]
  • Cancer and the Immune System an Overview of Recent Publications Featuring Illumina® Technology 2 Cancer and the Immune System TABLE of CONTENTS
    Cancer and the Immune System An Overview of Recent Publications Featuring Illumina® Technology 2 Cancer and the Immune System TABLE OF CONTENTS 04 Introduction 05 Dendritic cells 07 T-Cell Repertoire 09 Intratumoral T-Cells 11 Single Cells and TCR Sequencing 14 Cancer antigens 18 Cancer Immunoediting 20 Tumor Microenvironment 22 Cancer Immunotherapy 25 Hematological Malignancies 28 Tracking Malignant Lymphocytes 30 Bibliography Cancer and the Immune System 3 INTRODUCTION Advances in high-throughput sequencing have dramatically improved our knowledge of the cancer genome and the intracellular mechanisms involved in tumor progression and response to treatment. While the primary focus to date has been on the cancer cell, this technology can also be used to understand the interaction of the tumor cells and the cells in the surrounding tumor microenvironment. The tumor microenvironment is defined as the cellular environment in which the tumor exists. This includes surrounding blood vessels, immune cells, fibroblasts, other cells, signaling molecules, and the extracellular matrix. Expression analysis of the RNA levels can be used to determine the activation of pathways in the tumor microenvironment. Since common signaling pathways are involved in manifestation of several hallmarks of cancer, including cancer cell proliferation, survival, invasion, metastasis, and immunosuppression, targeting these shared signaling pathways in combination with immunotherapy may be a promising strategy for cancer treatment1. It is important to note that RNA-seq has the potential to track the activation of individual clones, which could ultimately lead to personalized treatment2,3. The human adaptive immune system provides protection against an enormous variety of pathogens and well as tumors.
    [Show full text]
  • Minimal Residual Disease Detection in Mantle Cell Lymphoma
    Original Article Minimal residual disease detection in mantle cell lymphoma: methods and significance of four-color flow cytometry compared to consensus IGH-polymerase chain reaction at initial staging and for follow-up examinations Sebastian Böttcher,1 Matthias Ritgen,1 Sebastian Buske,1 Stefan Gesk,2 Wolfram Klapper,3 Eva Hoster,4 Wolfgang Hiddemann,4 Michael Unterhalt,4 Martin Dreyling,4 Reiner Siebert,2 Michael Kneba,1 and Christiane Pott1 on behalf of the EU MCL MRD Group 1University of Schleswig-Holstein, Campus Kiel, 2nd Department of Medicine, Kiel, Germany; 2University of Schleswig-Holstein, Campus Kiel, Institute of Human Genetics, Kiel, Germany; 3Department of Haematopathology and Lymph Node Registry Kiel, University of Schleswig-Holstein, Campus Kiel, Germany and 4Department of Internal Medicine III, University of Munich, Hospital Grosshadern, Munich, Germany Citation: Böttcher S, Ritgen M, Buske S, Gesk S, Klapper W, Hoster E, Hiddemann W, Unterhalt M, Dreyling M, Siebert R, Kneba M and Pott C on behalf of the EU MCL MRD Group. Minimal residual disease detection in mantle cell lymphoma: methods and significance of four-color flow cytometry compared to consensus IGH-polymerase chain reaction at initial staging and for follow-up examinations. Haematologica 2008 Apr; 93(4):XXX-XXX. doi: 10.3324/haematol.11267 Treatment protocols as published by the BIOMED-2 Concerted Action.3 FAM- labeled PCR products were size separated on a high-resolu- Untreated patients with Ann Arbor stage II to IV MCL tion polyacrylamide gel and laser-induced fluorescence ana- were eligible for inclusion in the trials. Computed tomogra- lyzed using an ABI 310 genetic analyzer (Applied phy (CT) examinations of neck, chest, abdomen, and pelvis Biosystems, ABI, Darmstadt, Germany) as described previ- as well as bone marrow biopsies for cytology and histology ously (GeneScanning).4 In case of a polyclonal signal after (in general assessed by local pathologists) were mandatory FR1-IGH PCR, FR2- and FR3-IGH primer sets were used in for initial staging.
    [Show full text]
  • Regulatory Considerations for Use of Minimal Residual Disease in Development of Drug and Biological Products for Treatment Guidance for Industry
    Hematologic Malignancies: Regulatory Considerations for Use of Minimal Residual Disease in Development of Drug and Biological Products for Treatment Guidance for Industry U.S. Department of Health and Human Services Food and Drug Administration Oncology Center of Excellence (OCE) Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER) January 2020 Clinical/Medical Hematologic Malignancies: Regulatory Considerations for Use of Minimal Residual Disease in Development of Drug and Biological Products for Treatment Guidance for Industry Additional copies are available from: Office of Communications, Division of Drug Information Center for Drug Evaluation and Research Food and Drug Administration 10001 New Hampshire Ave., Hillandale Bldg., 4th Floor Silver Spring, MD 20993-0002 Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353; Email: [email protected] https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs and/or Office of Communication, Outreach, and Development Center for Biologics Evaluation and Research Food and Drug Administration 10903 New Hampshire Ave., Bldg. 71, Room 3128 Silver Spring, MD 20993-0002 Phone: 800-835-4709 or 240-402-8010; Email: [email protected] https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics- guidances U.S. Department of Health and Human Services Food and Drug Administration Oncology Center of Excellence (OCE) Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER) January 2020 Clinical/Medical TABLE OF CONTENTS I. INTRODUCTION............................................................................................................. 1 II. BACKGROUND ............................................................................................................... 2 III. DEVELOPMENT OF MRD AS A BIOMARKER FOR REGULATORY USE ........ 3 A. Regulatory Uses of Biomarkers ...................................................................................................
    [Show full text]
  • Monitoring Minimal Residual Disease and Predicting Relapse in APL By
    Leukemia (2001) 15, 1060–1065 2001 Nature Publishing Group All rights reserved 0887-6924/01 $15.00 www.nature.com/leu Monitoring minimal residual disease and predicting relapse in APL by quantitating PML-RARα transcripts with a sensitive competitive RT-PCR method K Tobal, H Moore, M Macheta and JA Liu Yin Molecular Oncology Group, University Department of Haematology, Manchester Royal Infirmary, Manchester M13 9WL, UK Qualitative RT-PCR methods used for monitoring minimal for diagnosis and in monitoring minimal residual disease residual disease (MRD) in APL patients fail to predict relapse (MRD).5–12 Serial negative tests for the PML-RARα transcripts in up to 25% of patients in remission. We report here the devel- opment and evaluation of a highly sensitive (10−5 and 10−6 with in post-chemotherapy patients are generally associated with one round and two rounds of PCR, respectively) competitive prolonged remission. However, up to 25% of those patients RT-PCR method to quantitate the PML-RARα fusion transcripts. can relapse within a short period of testing negative.10–13 This PML-RARα transcript’s levels were normalised to 105 copies of is due in part to the low level of sensitivity of these methods, ABL transcript. Serial BM and PB samples from 16 patients with approximately 10−4, which is 2 log lower than corresponding APL and t(15;17) were examined. Presentation samples from methods for other fusion genes such as AML1-MTG8.14 These three patients (three BM, one PB) showed levels in the range of 0.7 × 106–3.5 × 106 and 1.2 × 105 molecules in BM and PB methods lack the necessary sensitivity to detect the presence samples respectively.
    [Show full text]
  • Minimal Residual Disease (MRD) AHS-M2175
    Corporate Medical Policy Minimal Residual Disease (MRD) AHS-M2175 File Name: minimal_residual_disease_mrd Origination: 11/2020 Last CAP Review: 8/2021 Next CAP Review: 8/2022 Last Review: 8/2021 Description of Procedure or Service Minimal residual disease, also called measurable residual disease or MRD, refers to the subclinical levels of residual diseases, such as acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and multiple myeloma (MM) (Horton & Steuber, 2020; Larson, 2020; Rajkumar, 2020; Stock & Estrov, 2020a, 2020b). MRD is a postdiagnosis, prognostic indicator that can be used for risk stratification and to guide therapeutic options when used alongside other clinical and molecular data (Schuurhuis et al., 2018). Many different techniques have been developed to detect residual disease; however, PCR-based techniques, multicolor flow cytometry, and deep sequencing-based MRD generally provide better sensitivity, specificity, reproducibility, and applicability than other techniques, such as fluorescence in situ hybridization (FISH), Southern blotting, or cell culture (Stock & Estrov, 2020b). Related Policies: Flow Cytometry AHS-F2019 Genetic Testing for Acute Myeloid Leukemia AHS-M2062 Genetic Cancer Susceptibility Using Next Generation Sequencing AHS-M2066 ***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 minimal residual disease 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.
    [Show full text]
  • Minimal Residual Disease in Acute Lymphoblastic Leukemia: Current Practice and Future Directions
    cancers Review Minimal Residual Disease in Acute Lymphoblastic Leukemia: Current Practice and Future Directions Gloria Paz Contreras Yametti 1,2 , Talia H. Ostrow 2, Sylwia Jasinski 1,2, Elizabeth A. Raetz 1,2, William L. Carroll 1,2,* and Nikki A. Evensen 2 1 Division of Pediatric Hematology Oncology, NYU Langone Health, New York, NY 10016, USA; [email protected] (G.P.C.Y.); [email protected] (S.J.); [email protected] (E.A.R.) 2 Department of Pediatric and Pathology, Perlmutter Cancer Center, NYU Langone Health, Smillow 1211, 560 First Avenue, New York, NY 10016, USA; [email protected] (T.H.O.); [email protected] (N.A.E.) * Correspondence: [email protected]; Tel.: +1-212-263-9247 Simple Summary: Acute lymphoblastic leukemia minimal residual disease (MRD) refers to the presence of residual leukemia cells following the achievement of complete remission, but below the limit of detection using conventional morphologic assessment. Up to two thirds of children may have MRD detectable after induction therapy depending on the biological subtype and method of detection. Patients with detectable MRD have an increased likelihood of relapse. A rapid reduction of MRD reveals leukemia sensitivity to therapy and under this premise, MRD has emerged as the strongest independent predictor of individual patient outcome and is crucial for risk stratification. However, it is a poor surrogate for treatment effect on long term outcome at the trial level, with impending need of randomized trials to prove efficacy of MRD-adapted interventions. Citation: Contreras Yametti, G.P.; Ostrow, T.H.; Jasinski, S.; Raetz, E.A.; Abstract: Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer and advances Carroll, W.L.; Evensen, N.A.
    [Show full text]
  • Molecular Detection of Minimal Residual Disease Is a Strong Predictive Factor of Relapse in Childhood B-Lineage Acute Lymphoblastic Leukemia with Medium Risk Features
    Leukemia (2000) 14, 1939–1943 2000 Macmillan Publishers Ltd All rights reserved 0887-6924/00 $15.00 www.nature.com/leu Molecular detection of minimal residual disease is a strong predictive factor of relapse in childhood B-lineage acute lymphoblastic leukemia with medium risk features. A case control study of the International BFM study group A Biondi1, MG Valsecchi2, T Seriu3, E D’Aniello1, MJ Willemse4, K Fasching5, A Pannunzio1, H Gadner5, M Schrappe3, WA Kamps6, CR Bartram3, JJM van Dongen4 and ER Panzer-Gru¨mayer5 1Clinica Pediatrica Universita` di Milano-Bicocca, Ospedale S Gerardo, Monza, Italy; 2Department of Medicine and Public Health, Universita` di Verona, Italy; 4Department of Immunology, Erasmus University Rotterdam, Rotterdam, The Netherlands; 3Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany; 5Children’s Cancer Research Institute, St Anna Kinderspital, Vienna, Austria; and 6Dutch Childhood Leukemia Study Group (DCLSG), The Hague, The Netherlands The medium-risk B cell precursor acute lymphoblastic leuke- abnormalities) features at diagnosis3,4 and the evaluation of mia (ALL) accounts for 50–60% of total childhood ALL and early response to pre-phase treatment.5,6 comprises the largest number of relapses still unpredictable with diagnostic criteria. To evaluate the prognostic impact of The medium-risk group (MRG) represents a rather hetero- 1,7 minimal residual disease (MRD) in this specific group, a case genous cohort of patients. In the recently closed national control study was performed in patients classified and treated studies of the Austrian and German Berlin–Frankfurt–Mu¨nster as medium (or intermediate)-risk according to the criteria of (BFM) group (ALL-BFM 90),8 the Associazione Italiana di national studies (ALL-BFM 90, DCLSG protocol ALL-8, Ematologia e Oncologia Pediatrica (AIEOP-ALL 91)9 or the AIEOP-ALL 91), which includes a good day 7 treatment response.
    [Show full text]
  • Genomics, Transcriptomics, and Minimal Residual Disease Detection
    VIEWS IN THE SPOTLIGHT Genomics, Transcriptomics, and Minimal Residual Disease Detection: The Winning Team to Guide Treatment of Acute Lymphoblastic Leukemia Heidi Segers1,2 and Jan Cools3,4 Summary: Cytogenetics supported by additional molecular analyses and minimal residual disease detection have been successfully combined to improve the outcome of childhood acute lymphoblastic leukemia (ALL). Results from the St. Jude Total Therapy Study 16 demonstrate that some of the recently identified ALL subtypes can further guide risk stratification. See related article by Jeha et al. (8). Childhood acute lymphoblastic leukemia (ALL) is the that outcomes of patients with ALL with intermediate or high most common pediatric cancer and is now associated with levels of MRD at end of induction and consolidation could good treatment response and long-term survival for most be improved with therapy intensification (3). These findings patients. Over the past 50 years, the 5-year overall survival were also confirmed in the UKALL 2003 study, which showed has increased from less than 50% to more than 90% (1). This that therapy reduction could be done safely in patients with major improvement has been achieved by optimizing chemo- ALL with favorable MRD at end of induction, while children therapy regimens, improved supportive care, and better risk with persistent MRD at the end of induction had benefit stratification based on genetics, clinical characteristics at from intensified postremission therapy (4). Importantly, the diagnosis, and early treatment response measured by mini- UKALL 2003 study demonstrated that the relapse risk associ- mal residual disease (MRD). However, despite this success, ated with a specific MRD level varied according to the genetic there are still subtypes of ALL with less favorable outcome.
    [Show full text]