Myelodysplastic syndromes Impact of Biology. Lionel Adès Hopital Saint Louis Groupe Francophone des SMD. Épidémiologie
|
|
- Joseph Melton
- 6 years ago
- Views:
Transcription
1 Myelodysplastic syndromes Impact of Biology Lionel Adès Hopital Saint Louis Groupe Francophone des SMD Épidémiologie Incidence : 3 à 6 / hab. / An Prédomine chez les sujets âgés Augmentation de prévalence avec l âge ans : 3 à 15 / Hab. / an > 80 ans : 80 / Hab. / an Neukirchen, Leuk Res, % des anémies du sujet âge (Guralink, Blood, 2004) 1
2 MDS : Etiologies Age : +++ > 60 ans Expositions toxiques : Radiations ionisantes Chimiothérapies Tabac, Liés à Pathologie sous-jacente : Maladie de Fanconi Aplasie médullaire, Putative Pathogenetic Mechanisms and Their Interaction in the Myelodysplastic Syndromes Tefferi A, Vardiman J. N Engl J Med 2009;361:
3 Clonal evolution in MDS Walter, NEJM 2012 Prognostic factor of MDS 3
4 Scoring system Several scoring system Mostly designed in untreated patients Based on simple clinical parameters IPSS WPSS IPSS-R Among others International Prognostic Scoring System Prognostic Variable (points) Bone marrow blasts (%) < 5% 5-10 % % 21-30% 4 categories Cytopenias : - platelets < ⁹ /L - Hemoglobin < 10 g/dl - ANC < ⁹ /L 0/1 2/3 2 categories Cytogenetic Good: - Normal - -Y - del(5q) - del(20q) Intermediate: - other abnorm Poor: - Complex 3 abnorm - Chr 7 abnorm 3 categories 7 Subgroups Greenberg Blood
5 International Prognostic Scoring System Survival AML Evolution Greenberg Blood 1997 New cytogenetic classification Survival 2,902 patients AML Evolution 5
6 New cytogenetic classification Revised IPSS (IPSS-R) points blasts ( %) 2% - 2-4% % >10% Hemoglobin >10 g/dl 8-10 g/dl <8 g/dl ANC >0.8 G/l <0/8 G/l 4 categories 3 categories 2 categories Platelet > <50 3 categories Cytogenetics Very Good -Y del(11q) Good Normal der(1;7) del(5q) del(20q) del(12p) Double incl del(5q) Intermed -7/7q +8 Iso(17q) other double inclusions Poor: der3q(21) der3q(26) Complex Double inclusion 7q/7 Very Poor Complex >3 5 categories 16 subgroups P. Greenberg et al, Blood
7 IPSS-R Survie Transformation LAM IPSS-R Some low risk MDS patient according to IPSS might be Reclassied has Having Higher Risk MDS According to IPSS-R P. Greenberg et al, Blood
8 Treatment 15 Treatment : Based on IPSS Malcovati et al, Blood
9 Treatment : Based on IPSS Malcovati et al, Blood Room for improvement 18 9
10 Frequency of mutations 51% of MDS patients had at least one identified mutation 52% of cases with normal karyotype had at least one mutation Bejar et al, NEJM 2011 Splicing mutations Yoshida Nature
11 Many more oncogenetic events 111 genes in 838 patients Mutations observed in 80% of the cases Elli Papaemmanuil, Blood 2013 Several Pathways MDS EZH2 DNMT3A EPIGENETIC REGULATION TET2 ASXL1 IDH1 et 2 UTX SETBP
12 Several Pathways MDS EZH2 DNMT3A SF3B1 U2AF1 EPIGENETIC REGULATION ASXL1 TET2 IDH1 et 2 ZRS F2 SPLICING SRSF2 UTX SETBP1 23 Several Pathways JAK2 PTPN11 BRAF TYROSINE KINASE KRAS NRAS CBL MDS EZH2 DNMT3A SF3B1 U2AF1 EPIGENETIC REGULATION ASXL1 TET2 IDH1 et 2 ZRS F2 SPLICING SRSF2 UTX SETBP
13 Several Pathways JAK2 PTPN11 TYROSINE KINASE BRAF KRAS NRAS CBL RUNX1 GATA2 TRANSCRIPTION ETV6 WT1 MDS EZH2 DNMT3A SF3B1 U2AF1 EPIGENETIC REGULATION SPLICING TET2 IDH1 et 2 ASXL1 ZRS F2 SRSF2 UTX SETBP1 25 Several Pathways JAK2 PTPN11 BRAF NPM1 RUNX1 GATA2 TYROSINE KINASE TRANSCRIPTION OTHERS KRAS ETV6 NRAS WT1 CBL TP53 BCOR MDS EZH2 DNMT3A SF3B1 U2AF1 EPIGENETIC REGULATION SPLICING TET2 IDH1 et 2 ASXL1 ZRS F2 SRSF2 UTX SETBP
14 Mutation mutually exclusive Point Mutation Cytogenetic Elli Papaemmanuil, Blood 2013 Co-mutated Mutually exclusive Transcription DNA Methylation Splicing Signalling Chromatin Other Mutually exclusive gene pairs often imply functional redundancy, especially if such genes are in the same biological pathway 27 Co occurrence of mutations Splicing 50% and Epigenetic genes 45% Splicing Epigenetic Mutation TP53 No Mutation Other Mutation 28 14
15 Impact to Stratify MDS? Impact on OS Clinical Correlations Mutations and Survival Bejar et al, NEJM
16 Impact on OS Bejar et al, NEJM 2011 Add new information to IPSS Bejar et al, NEJM
17 Probabilité de Survie sans Leucémie 28/01/2016 Impact of the number of mutation Pas de mutation 1 mutation 2 mutations 3 mutations 4-5 mutations 6 ou plus mutations Temps (mois) Elli Papaemmanuil, Blood 2013 Impact in treated patients? 17
18 Cytogentics Impact of Cytogenetics on OS compared to NK in 931 treated pts Cytogenetic n Hazard Ratio (95% CI) Reference Better -1 Worse 1 4 M. Sebert et al., ASH
19 Gene mutations Impact of TET2 mutation in patients treated with AZA all TET2 mutated TET2 WT p* Patients (17%) 86 (83%) Cycles of AZA 7 [1-39] 11 [4-34] 6 [1-39] 0,016 High risk cytogenetics 30 (34%) 1 (7%) 29 (39%) 0,01 Complete Response 24 (23%) 7 (41%) 17 (20%) 0,07 ORR (including HI) 53 (52%) 14 (82%) 39 (45%) 0,007 Higher Response Rate in TET 2 mutated patients Response duration and overall survival were, however, comparable in the MUT and WT groups. R. Itzykson et al. 19
20 Impact of TP53 in AZA treated pts TP53: 35-40% mutations By deep-sequencing Bally Leuk Res 2014; Walter Leukemia 2013 Impact of mutations in pts treated with HMA DFS OS HR IC 95 p HR IC 95 p Mutation status Methylation patway genes - TET2 (wt vs mutated) - DNMT3A (wt vs mutated) - IDH1/IDH2 (wt vs mutated) - TET2/DNMT3A (both wt vs one or both mutated) - TET2/DNMT3A/IDH1/IDH2 (all wt vs 1 mutation) 1,33 1,14 0,82 1,29 1,10 0,73-2,43 0,49-2,64 0,35-1,90 0,76-2,21 0,67-1,82 0,35 0,76 0,64 0,35 0,70 1,10 1,21 0,62 1,17 1,02 0,57-2,13 0,48-3,01 0,25-1,56 0,65-2,08 0,59-1,76 0,76 0,68 0,31 0,61 0,96 Histone-modifying gene ASXL1 (wt vs mutated) 0,68 0,41-1,12 0,13 0,48 0,28-0,82 0,008 Signal transduction genes CBL (wt vs mutated) CBL /RAS (wt vs mutated) 0,26 1,69 0,08-0,85 0,53-5,41 0,03 0,37 0,41 1,81 0,10-1,72 0,44-7,46 Spliceosomal gene SF3B1 (wt vs mutated) 1,95 0,93-4,08 0,08 3,76 1,36-10,42 0,01 0,22 0,41 Traina et al., Leukemia
21 Impact in HR MDS treated patients Role of TP53 in del(5q) patients TP53 mutations with a median clone size of 11% (range, 1% to 54%) were detected in 10 patients (18%) already at an early phase of the disease. Associated with evolution to acute myeloid leukemia. The probability of a complete cytogenetic response to lenalidomide was lower in mutated patients Jadersten M et al., JCO
22 Impact of mutation in Lower risk MDS Park et al. Soumis Genetic-driven treatment? 22
23 Some Drugable mutations? JAK2 PTPN11 BRAF RUNX1 GATA2 NPM1 NRAS CBL KRAS WT1 ETV6 BCOR TP53 MDS EZH2 DNMT3A SF3B1 U2AF1 TET2 IDH1 et 2 ASXL1 ZRS F2 SRSF2 UTX SETBP1 45 Drugable? Study Drug disease n Response Ref JAK2 Phase II Ruxolitinib AML 18 2 CR 1 CRi Case report Case report Ruxolitinib Azacytidine Ruxolitinib 7+3 IDH2 Phase I AG-221 Myeloid malignanc ies TP53 Phase Ib RG7388 MDM2 inhibitor 3 2 responses AML 6 2 CR 2 PR Lundberg, Blood 2014 Mwirigi, BJH 2014 Cluzeau, BJH % de Botton, ASH 2014 AML 88 15% Yee, ASH 2014 BCL2 Phase II ABT199 AML/MDS 32 19% Konopleva, ASH
24 Many oncogenetic events Do we really expect to have One drug for each oncogenetic Event? Elli Papaemmanuil, Blood 2013 Mutations in patients without Hematological Malignacies NEJM 2014; 371:
25 Drug targeting pathways Tipifarnib MAPK inhibitor MAPK Histone Deacetylase Inhibitor Me Me H3 Me MAP PI3K Hypomethylating Agents PI3K Inhibitor Bcl2 P53 inhibitor 49 Other Pathways BFU-E CFU-E Pro E Baso E Poly E Ortho E Retic RBC EPO drives proliferation GDF11 (TGF beta family) and the GDF11-ActRIIB- Smad2/3 pathway in the late stage of Erythropoiesis Mouse model of MDS: Murine ACE-536 (RAP-536) increased hemoglobin levels and decreased bone marrow erythroid hyperplasia (Suragani R et al., Nature Med 2014) Phase 1 study: ACE-536 well tolerated and dose-dependent increase in Hemoglobin (Attie K et al., Am J Hematol 2014) 25
26 TGFB inhibitors Key Role of GDF11 (TGF beta family) and the GDF11-ActRIIB- Smad2/3 pathway in the late stage of Erythropoiesis Luspatercept (Phase II) Mean (SD) Max. Change in Hemoglobin (g/dl) 4,0 3,0 2,0 1,0 0,0 Efficacy +++ in SF3B1 mutated patients 0, (n=1) 1,0 2, (n=1) (n=3) Dose Group (mg/kg) 3, (n=2) 26
27 Conclusions Several mutated genes in different Pathways are involved in MDS Some Serve as prognostic marker Might help for a better definition of the disease and Might Serve in the future as target to new therapeutic drugs Toward a personalized medicine but the road is still long!! 53 27
Myelodysplastic Syndromes. Post-ASH meeting 2014 Marie-Christiane Vekemans
Myelodysplastic Syndromes Post-ASH meeting 2014 Marie-Christiane Vekemans Agenda New biological developments Risk assessment and prognostic factors New therapeutic options Agenda New biological developments
More informationMutational Impact on Diagnostic and Prognostic Evaluation of MDS
Mutational Impact on Diagnostic and Prognostic Evaluation of MDS Elsa Bernard, PhD Papaemmanuil Lab, Computational Oncology, MSKCC MDS Foundation ASH 2018 Symposium Disclosure Research funds provided by
More informationMolecular Genetic Testing to Predict Response to Therapy in MDS
Molecular Genetic Testing to Predict Response to Therapy in MDS Rafael Bejar MD, PhD Bone Marrow Failure Disease Scientific Symposium Rockville, MD March 18 th, 2016 Overview Response Criteria Lenalidomide
More informationManagement of Myelodysplastic Syndromes
Management of Myelodysplastic Syndromes Peter L. Greenberg, MD Stanford Cancer Institute Myelodysplastic Syndromes: Clinical & Molecular Advances for Disease Classification and Prognostication MDSs: A
More informationEmerging Treatment Options for Myelodysplastic Syndromes
Emerging Treatment Options for Myelodysplastic Syndromes James K. Mangan, MD, PhD Assistant Professor of Clinical Medicine Abramson Cancer Center, University of Pennsylvania Please note that some of the
More informationTreatment of low risk MDS
Treatment of low risk MDS Matteo G Della Porta Cancer Center IRCCS Humanitas Research Hospital & Humanitas University Rozzano Milano, Italy matteo.della_porta@hunimed.eu International Prognostic Scoring
More informationMyelodysplastic syndromes post ASH Dominik Selleslag AZ Sint-Jan Brugge
Myelodysplastic syndromes post ASH 2016 Dominik Selleslag AZ Sint-Jan Brugge Why did they put MDS at the end of the meeting? Possible explanations Least fascinating disease without progress? Poor speaker?
More informationNext Generation Sequencing in Haematological Malignancy: A European Perspective. Wolfgang Kern, Munich Leukemia Laboratory
Next Generation Sequencing in Haematological Malignancy: A European Perspective Wolfgang Kern, Munich Leukemia Laboratory Diagnostic Methods Cytomorphology Cytogenetics Immunophenotype Histology FISH Molecular
More informationConcomitant WT1 mutations predicted poor prognosis in CEBPA double-mutated acute myeloid leukemia
Concomitant WT1 mutations predicted poor prognosis in CEBPA double-mutated acute myeloid leukemia Feng-Ming Tien, Hsin-An Hou, Jih-Luh Tang, Yuan-Yeh Kuo, Chien-Yuan Chen, Cheng-Hong Tsai, Ming Yao, Chi-Cheng
More informationMyelodysplastic Syndromes: Understanding your diagnosis and current and emerging treatments
Myelodysplastic Syndromes: Understanding your diagnosis and current and emerging treatments Shyamala Navada, M.D., MSCR Assistant Professor Icahn School of Medicine at Mount Sinai Tisch Cancer Institute
More informationEmerging Treatment Options for Myelodysplastic Syndromes
Emerging Treatment Options for Myelodysplastic Syndromes James K. Mangan, MD, PhD Assistant Professor of Clinical Medicine Abramson Cancer Center, University of Pennsylvania Please note that some of the
More informationPathogenesis and management of CMML
Pathogenesis and management of CMML Raphaël Itzykson, Hôpital Saint-Louis, Paris International Conference of the Korean Society of Hematology March 29th 2018 대한혈액학회 Korean Society of Hematology COI disclosure
More informationLow Risk MDS Scoring System. Prognosis in Low Risk MDS. LR-PSS Validation 9/19/2012
Advances in MDS What s on the Horizon Tapan M. Kadia, MD Department of Leukemia MD Anderson Cancer Center Outline Newer Prognostic Systems Hypomethylating agent failures Newer Treatment approaches Role
More informationMyelodysplastic syndrome is a highly heterogeneous hematopoietic
SHORT COMMUNICATION Clinical Characteristics and Prognosis of 48 Patients with Mutations in Myelodysplastic Syndrome Yulu Tian #, Ruijuan Zhang #, Linhua Yang* Yang L. Clinical Characteristics and Prognosis
More informationEmerging Treatment Options for Myelodysplastic Syndromes
Emerging Treatment Options for Myelodysplastic Syndromes James K. Mangan, MD, PhD Assistant Professor of Clinical Medicine Abramson Cancer Center, University of Pennsylvania Please note that some of the
More informationPrecision Medicine and Molecular Testing.
Precision Medicine and Molecular Testing. David A. Sallman, MD Assistant Member Department of Malignant Hematology Moffitt Cancer Center david.sallman@moffitt.org Disclosures Research funding for Celgene
More informationASBMT MDS/MPN Update Sunil Abhyankar, MD
ASBMT MDS/MPN Update Sunil Abhyankar, MD Professor of Medicine Medical Director, Pheresis and Cell Processing Division of Hematologic Malignancies and Cellular Therapeutics Department of Internal Medicine
More informationASBMT MDS/MPN UPDATE
ASBMT MDS/MPN UPDATE Sunil Abhyankar, MD Professor of Medicine Medical Director, Pheresis and Cell Processing Division of Hematologic Malignancies and Cellular Therapeutics Department of Internal Medicine
More informationMolecular profiling in confirming the diagnosis of early myelodysplastic syndrome
Molecular profiling of early MDS Hematopathology - March 2016 Article Molecular profiling in confirming the diagnosis of early myelodysplastic syndrome Maya Thangavelu 1,*, Ryan Olson 2, Li Li 2, Wanlong
More informationAPPROACH TO MYELODYSPLASTIC SYNDROMES IN THE ERA OF PRECISION MEDICINE
APPROACH TO MYELODYSPLASTIC SYNDROMES IN THE ERA OF PRECISION MEDICINE Rashmi Kanagal-Shamanna, MD Assistant Professor Hematopathology & Molecular Diagnostics Department of Hematopathology The University
More informationKevin Kelly, MD, Phd Acute Myeloid and Lymphoid Leukemias
Kevin Kelly, MD, Phd Acute Myeloid and Lymphoid Leukemias Relevant financial relationships in the past twelve months by presenter or spouse/partner. Speakers bureau: Novartis, Janssen, Gilead, Bayer The
More informationExamining Genetics and Genomics of Acute Myeloid Leukemia in 2017
Examining Genetics and Genomics of Acute Myeloid Leukemia in 2017 Elli Papaemmanuil, PhD Memorial Sloan Kettering Cancer Center New York, New York, United States Today s Talk Cancer genome introduction
More informationDISCLOSURE Luca Malcovati, MD. No financial relationships to disclose
ICUS, CCUS and CHIP Luca Malcovati, MD Department of Molecular Medicine, University of Pavia Medical School, & Department of Hematology Oncology, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy DISCLOSURE
More informationAnemia (2): 4 MS/18/02/2019
Anemia (2): 4 MS/18/02/2019 Case 2 65 yr old male had gradual onset of odd behavior with psychotic symptoms, irritability and parasthesia in hands and feet He was noticed to have imbalanced gait. Examination
More informationMyelodysplastic syndromes
Myelodysplastic syndromes Robert P Hasserjian Massachusetts General Hospital, Boston, MA Disclosure of Relevant Financial Relationships Dr. Hasserjian declares he has no conflict(s) of interest to disclose.
More informationMDS 101. What is bone marrow? Myelodysplastic Syndrome: Let s build a definition. Dysplastic? Syndrome? 5/22/2014. What does bone marrow do?
101 May 17, 2014 Myelodysplastic Syndrome: Let s build a definition Myelo bone marrow Gail J. Roboz, M.D. Director, Leukemia Program Associate Professor of Medicine What is bone marrow? What does bone
More informationAcute Myeloid Leukemia Progress at last
Acute Myeloid Leukemia Progress at last Bruno C. Medeiros, MD September 9, 217 Introduction Mechanisms of leukemogenesis Emerging therapies in AML Previously untreated AML Relapsed and refractory patients
More informationNew and Emerging Strategies in the Treatment of Patients with Higher risk Myelodysplastic Syndromes (MDS)
Welcome to Managing Myelodysplastic Syndromes. My name is David Steensma. I am an Associate Professor of Medicine at Harvard Medical School and a faculty member in the Adult Leukemia Program at Dana Farber
More informationNovità nelle MDS. Matteo G Della Porta. Cancer Center IRCCS Humanitas Research Hospital & Humanitas University Rozzano Milano, Italy
Novità nelle MDS Matteo G Della Porta Cancer Center IRCCS Humanitas Research Hospital & Humanitas University Rozzano Milano, Italy matteo.della_porta@hunimed.eu Outline ARCH Predictive value of somatic
More informationMyelodysplastic syndromes: 2018 update on diagnosis, risk-stratification and management
Received: 2 October 2017 Accepted: 2 October 2017 DOI: 10.1002/ajh.24930 ANNUAL CLINICAL UPDATES IN HEMATOLOGICAL MALIGNANCIES Myelodysplastic syndromes: 2018 update on diagnosis, risk-stratification and
More informationMyelodysplastic Syndromes:
Incidence Rate per 100,000 7/21/2015 Myelodysplastic Syndromes: Current Thinking on the Disease, Diagnosis and Treatment Rafael Bejar MD, PhD Aplastic Anemia & MDS International Foundation Regional Patient
More informationOverview. Myelodysplastic Syndromes: What s on the Horizon? Molecular Mutations in MDS. Refining Risk Models. Incorporating Mutational Data
Myelodysplastic Syndromes: What s on the Horizon? Vu H. Duong, MD, MS Assistant Professor of Medicine University of Maryland July 16, 2016 Overview Refining Risk models Specific Therapeutic Areas of Need
More informationNew treatment strategies in myelodysplastic syndromes and acute myeloid leukemia van der Helm, Lidia Henrieke
University of Groningen New treatment strategies in myelodysplastic syndromes and acute myeloid leukemia van der Helm, Lidia Henrieke IMPORTANT NOTE: You are advised to consult the publisher's version
More informationMyelodysplastic syndromes: revised WHO classification and distinction from non-neoplastic conditions
Myelodysplastic syndromes: revised WHO classification and distinction from non-neoplastic conditions Robert P Hasserjian, MD Associate Professor Massachusetts General Hospital and Harvard Medical School
More informationPublished Ahead of Print on April 14, 2016, as doi: /haematol Copyright 2016 Ferrata Storti Foundation.
Published Ahead of Print on April 14, 2016, as doi:10.3324/haematol.2016.143214. Copyright 2016 Ferrata Storti Foundation. Immunohistochemical pattern of p53 is a measure of TP53 mutation burden and adverse
More informationBlast transformation in chronic myelomonocytic leukemia: Risk factors, genetic features, survival, and treatment outcome
RESEARCH ARTICLE Blast transformation in chronic myelomonocytic leukemia: Risk factors, genetic features, survival, and treatment outcome AJH Mrinal M. Patnaik, 1 Emnet A. Wassie, 1 Terra L. Lasho, 2 Curtis
More informationWhat you need to know about MDS. The Myelodysplastic Syndromes. Stuart Goldberg MD
What you need to know about MDS The Myelodysplastic Syndromes Stuart Goldberg MD The Myelodysplastic Syndromes are a group of bone marrow failure diseases The bone marrow is the factory that makes blood
More informationMyelodysplastic syndromes and the new WHO 2016 classification
Myelodysplastic syndromes and the new WHO 2016 classification 32nd General Annual Meeting of the Belgian Hematology Society 10-11 February 2017 Gregor Verhoef, Departement of Hematology, University Hospital
More informationSUPPLEMENTARY INFORMATION
Supplementary Information S1 Frequency of DNMT3A mutations in hematologic disorders and their associated clinical phenotypes. Disease Patient population Frequency (%) Associated Clinical Characteristics
More informationNew drugs in Acute Leukemia. Cristina Papayannidis, MD, PhD University of Bologna
New drugs in Acute Leukemia Cristina Papayannidis, MD, PhD University of Bologna Challenges to targeted therapy in AML Multiple subtypes based upon mutations/cytogenetic aberrations No known uniform genomic
More informationPiper Jaffray Healthcare Conference
Piper Jaffray Healthcare Conference John Scarlett, M.D. President and CEO, Geron Corporation November 2018 Forward-Looking Statements Except for statements of historical fact, the statements contained
More informationPrognostic Scoring Systems for Therapeutic Decision Making in MDS. Peter Greenberg, MD Stanford University Cancer Center Stanford, CA
Prognostic Scoring Systems for Therapeutic Decision Making in MDS Peter Greenberg, MD Stanford University Cancer Center Stanford, CA DISCLOSURE I have no relevant financial relationships to disclose. MDSs:
More informationNext generation sequencing analysis - A UK perspective. Nicholas Lea
Next generation sequencing analysis - A UK perspective Nicholas Lea King s HMDC LMH is part of an integrated pathology service at King s Haematological Malignancy Diagnostic Centre (HMDC) HMDC serves population
More informationEtiology. Definition MYELODYSPLASTIC SYNDROMES. De novo. Secondary MDS (10 years earlier than primary) transformation
MYELODYSPLASTIC SYNDROMES Rashmi Kanagal-Shamanna, MD Assistant Professor Hematopathology & Molecular Diagnostics The University of Texas M.D. Anderson Cancer Center Houston, Texas No relevant COIs to
More informationTET2 mutations were predictive of inferior prognosis in the presence of ASXL1 mutations in patients with chronic myelomonocytic leukemia
Short Report TET2 mutations were predictive of inferior prognosis in the presence of ASXL1 mutations in patients with chronic myelomonocytic leukemia Yajuan Cui 1,2 *, Hongyan Tong 3 *, Xin Du 4 *, Bing
More informationJuan Ma 1, Jennifer Dunlap 2, Lisong Shen 1, Guang Fan 2 1
Juan Ma 1, Jennifer Dunlap 2, Lisong Shen 1, Guang Fan 2 1 Xin Hua Hospital, Shanghai, China 2 Oregon Health & Science University, Portland, OR, United States AML is a hematopoietic neoplasms characterized
More informationSupplemental Material. The new provisional WHO entity RUNX1 mutated AML shows specific genetics without prognostic influence of dysplasia
Supplemental Material The new provisional WHO entity RUNX1 mutated AML shows specific genetics without prognostic influence of dysplasia Torsten Haferlach, 1 Anna Stengel, 1 Sandra Eckstein, 1 Karolína
More informationChronic Myelomonocytic Leukemia with molecular abnormalities SH
Chronic Myelomonocytic Leukemia with molecular abnormalities SH2017-0351 Madhu P. Menon MD,PhD, Juan Gomez MD, Kedar V. Inamdar MD,PhD and Kristin Karner MD Madhu P Menon, MD, PhD Henry Ford Hospital Patient
More informationIntro alla patologia. Giovanni Barosi. Fondazione IRCCS Policlinico San Matteo Pavia
Settima Giornata Fiorentina dedicata ai pazienti con malattie mieloproliferative croniche Sabato 13 Maggio 2017 CRIMM Centro di Ricerca e Innovazione per le Malattie Mieloproliferative AOU Careggi Intro
More informationUnderstanding & Treating Myelodysplastic Syndrome (MDS)
Understanding & Treating Myelodysplastic Syndrome (MDS) Casey O Connell, MD Associate Professor of Clinical Medicine Jane Anne Nohl Division of Hematology Keck School of Medicine of USC Let s Look at Our
More informationACCME/Disclosures. History. Hematopathology Specialty Conference Case #4 4/13/2016
Hematopathology Specialty Conference Case #4 Sherrie L. Perkins MD, PhD University of Utah ACCME/Disclosures The USCAP requires that anyone in a position to influence or control the content of CME disclose
More information7/12/2016 TESTING. Objectives. New Directions in Aplastic Anemia: What's on the Horizon? Better way to evaluate clonal evolution?
New Directions in Aplastic Anemia: What's on the Horizon? Amy E. DeZern, MD; MHS Assistant Professor Hematologic Malignancies Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, MD Objectives
More informationLa lenalidomide: meccanismo d azione e risultati terapeutici. F. Ferrara
La lenalidomide: meccanismo d azione e risultati terapeutici F. Ferrara MDS: new treatment goals Emerging treatment options expected to facilitate shift from supportive care to active therapy in MDS New
More informationTable 1: biological tests in SMD
Table 1: biological tests in SMD Tests Mandatory Recommended Under validation Morphology Marrow aspirate Marrow biopsy 1 Iron staining Quantification of dysplasia WHO 2008 Classification Cytogenetics Conventional
More informationCorporate Presentation. January 2019
Corporate Presentation January 2019 Forward-Looking Statements Except for statements of historical fact, the statements contained in this presentation are forward-looking statements made pursuant to the
More informationDisclosures for Ayalew Tefferi
Disclosures for Ayalew Tefferi Principal investigator role Employee Consultant Major Stockholder Speakers Bureau Scientific Advisory Board Janssen, Geron, Celgene, Sanofi-Aventis, Gilead Sciences, Incyte
More informationOut-Patient Billing CPT Codes
Out-Patient Billing CPT Codes Updated Date: August 3, 08 Client Billed Molecular Tests HPV DNA Tissue Testing 8764 No Medicare Billed - Molecular Tests NeoARRAY NeoARRAY SNP/Cytogenetic No 89 NeoLAB NeoLAB
More informationAcute Leukemia Diagnosis
Acute Leukemia Diagnosis Elizabeth A. Griffiths, MD Leukemia Service, Department of Medicine Roswell Park Cancer Institute SUNY-UB School of Medicine 3 841,390 843,820 Blood cancers are normal blood cells
More informationChi sono i candidati agli inibitori di JAK2
Chi sono i candidati agli inibitori di JAK2 Francesco Passamon, Hematology, University Hospital Varese, Italy Ruxoli8nib (US approved in MF; EAP study and compassionate use in Italy) SAR302503 (phase 3
More informationLet s Look at Our Blood
Let s Look at Our Blood Casey O Connell, MD Associate Professor of Clinical Medicine Jane Anne Nohl Division of Hematology Keck School of Medicine of USC 10,000,000,000 WBCs/day Bone Marrow: The Blood
More informationMyelodysplastic syndrome. Jeanne Palmer, MD Mayo Clinic, Arizona
Myelodysplastic syndrome Jeanne Palmer, MD Mayo Clinic, Arizona What is Myelodysplastic syndrome? A disease where the bone marrow doesn t work appropriately What does that mean?? Red blood cells Carry
More informationTreating Higher-Risk MDS. Case presentation. Defining higher risk MDS. IPSS WHO IPSS: WPSS MD Anderson PSS
Treating Higher-Risk MDS Eyal Attar, M.D. Massachusetts General Hospital Cancer Center eattar@partners.org 617-724-1124 Case presentation 72 year old man, prior acoustic neuroma WBC (X10 3 /ul) 11/08 12/08
More informationClonal Cytopenia and Myeloid Neoplasms
Clonal Cytopenia and Myeloid Neoplasms Luca Malcovati, MD Department of Molecular Medicine, University of Pavia Medical School, & Department of Hematology Oncology, IRCCS Policlinico S. Matteo Foundation,
More informationLaboratory Service Report
Specimen Type Peripheral blood CR PDF Report available at: https://test.mmlaccess.com/reports/c7028846-ih2xuglwpq.ashx Indication for Test DS CR Pathogenic utations Detected CR 1. JAK2: c.1849g>t;p.val617phe
More informationLeukemia and subsequent solid tumors among patients with myeloproliferative neoplasms
Leukemia and subsequent solid tumors among patients with myeloproliferative neoplasms Tiziano Barbui (tbarbui@asst-pg23.it Hematology and Research Foundation,Ospedale Papa Giovanni XXIII, Bergamo Italy
More informationBlastic Plasmacytoid Dendritic Cell Neoplasm with DNMT3A and TET2 mutations (SH )
Blastic Plasmacytoid Dendritic Cell Neoplasm with DNMT3A and TET2 mutations (SH2017-0314) Habibe Kurt, Joseph D. Khoury, Carlos E. Bueso-Ramos, Jeffrey L. Jorgensen, Guilin Tang, L. Jeffrey Medeiros, and
More informationOutline. Case Study 5/17/2010. Treating Lower-Risk Myelodysplastic Syndrome (MDS) Tapan M. Kadia, MD Department of Leukemia MD Anderson Cancer Center
Treating Lower-Risk Myelodysplastic Syndrome (MDS) Tapan M. Kadia, MD Department of Leukemia MD Anderson Cancer Center Outline Case Study What is lower-risk MDS? Classification systems Prognosis Treatment
More informationUpdate on Myelodysplastic Syndromes and Myeloproliferative Neoplasms. Kaaren Reichard Mayo Clinic Rochester
Update on Myelodysplastic Syndromes and Myeloproliferative Neoplasms Kaaren Reichard Mayo Clinic Rochester Reichard.kaaren@mayo.edu Nothing to disclose Conflict of Interest Learning Objectives Present
More informationShould Mutational Status in Primary Myelofibrosis (PMF) Guide Therapy..YES!!!
Should Mutational Status in Primary Myelofibrosis (PMF) Guide Therapy..YES!!! Lindsay Anne Magura Rein, MD Division of Hematologic Malignancies and Cellular Therapy/BMT A Little Bit of History.. 1665 Advanced
More informationThe preclinical efficacy of a novel telomerase inhibitor, imetelstat, in AML: A randomized trial in patient-derived xenografts
The preclinical efficacy of a novel telomerase inhibitor, imetelstat, in AML: A randomized trial in patient-derived xenografts Claudia Bruedigam, Ph.D Gordon and Jessie Gilmour Leukaemia Research Laboratory
More informationIllumina Trusight Myeloid Panel validation A R FHAN R A FIQ
Illumina Trusight Myeloid Panel validation A R FHAN R A FIQ G E NETIC T E CHNOLOGIST MEDICAL G E NETICS, CARDIFF To Cover Background to the project Choice of panel Validation process Genes on panel, Protocol
More informationSESSION 1 Reactive cytopenia and dysplasia
SESSION 1 Reactive cytopenia and dysplasia Falko Fend, Tübingen & Alexandar Tzankov, Basel 1 Disclosure of speaker s interests (Potential) conflict of interest none Potentially relevant company relationships
More informationAbnormal blood test Y E A R S. Diagnosis of MDS
Abnormal blood test 3 Y E A R S Diagnosis of MDS Demographics of Germany [90 2050] and Europe Italy Germany Spain Austria Greece eu5 Countrybyrankorder in203 Finland Portugal Belgium France UK Netherlands
More informationORIGINAL ARTICLE CLINICAL ONCOLOGY. J Cancer Res Clin Oncol (2017) 143: DOI /s
J Cancer Res Clin Oncol (2017) 143:873 882 DOI 10.1007/s00432-016-2331-0 ORIGINAL ARTICLE CLINICAL ONCOLOGY Decitabine priming prior to low-dose chemotherapy improves patient outcomes in myelodysplastic
More informationPublished Ahead of Print on June 22, 2017, as doi: /haematol Copyright 2017 Ferrata Storti Foundation.
Published Ahead of Print on June 22, 2017, as doi:10.3324/haematol.2017.166173. Copyright 2017 Ferrata Storti Foundation. Molecular analysis of myelodysplastic syndrome with isolated del(5q) reveals a
More informationMANAGEMENT OF ADULT PATIENTS WITH MYELODYSPLASTIC SYNDROMES
MANAGEMENT OF ADULT PATIENTS WITH MYELODYSPLASTIC SYNDROMES *Nicolas Bonadies Department of Haematology and Central Haematology Laboratory, Inselspital Bern, University Hospital, University of Bern, Bern,
More informationNeedham Healthcare Conference. John Scarlett, M.D. President & CEO, Geron Corporation March 27, 2018
Needham Healthcare Conference John Scarlett, M.D. President & CEO, Geron Corporation March 27, 2018 Forward-Looking Statements Except for the historical information contained herein, this presentation
More informationRandomized phase 2 study of low-dose decitabine vs low-dose azacitidine in lower-risk MDS and MDS/MPN
Regular Article CLINICAL TRIALS AND OBSERVATIONS Randomized phase 2 study of low-dose decitabine vs low-dose azacitidine in lower-risk MDS and MDS/MPN Elias Jabbour, 1 Nicholas J. Short, 1 Guillermo Montalban-Bravo,
More informationRefining Prognosis. Overview. Low Blood Counts. Low Blood Counts. High Risk MDS and Novel Therapy: What s on the Horizon? 3/2/2016
High Risk MDS and Novel Therapy: What s on the Horizon? Rafael Bejar MD, PhD Aplastic Anemia & MDS International Foundation Regional Patient and Family Conference March 19 th, 216 Overview Refining Prognosis
More informationThe Center for PERSONALIZED DIAGNOSTICS
The Center for PERSONALIZED DIAGNOSTICS Precision Diagnostics for Personalized Medicine A joint initiative between The Department of Pathology and Laboratory Medicine & The Abramson Cancer Center The (CPD)
More informationDepartment of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, Texas; 2 Sunesis Pharmaceuticals, Inc, South San Francisco
Phase I/II Study of Vosaroxin and Decitabine in Newly Diagnosed Older Patients with Acute Myeloid Leukemia (AML) and High Risk Myelodysplastic Syndrome (MDS) Naval Daver 1, Hagop Kantarjian 1, Guillermo
More informationSession 4: Summary and Conclusions
Session 4: Summary and Conclusions Total cases in Session 4 Myeloproliferative neoplasms 16 cases Oral #300 (CEL, NOS) Mastocytosis 2 cases Oral #156 (SM-AHN) Myeloid/lymphoid neoplasms with eosinophilia
More informationLaboratory Service Report
Client C7028846-DLP Rochester Rochester, N 55901 Specimen Type Peripheral blood CR PDF Report available at: https://test.mmlaccess.com/reports/c7028846-zwselwql7p.ashx Indication for Test DS CR Pathogenic
More informationMYELODYSPLASTIC SYNDROMES: A diagnosis often missed
MYELODYSPLASTIC SYNDROMES: A diagnosis often missed D R. EMMA W YPKEMA C O N S U LTA N T H A E M AT O L O G I S T L A N C E T L A B O R AT O R I E S THE MYELODYSPLASTIC SYNDROMES DEFINITION The Myelodysplastic
More informationMayo alliance prognostic system for mastocytosis: clinical and hybrid clinical-molecular models
REGULAR ARTICLE Mayo alliance prognostic system for mastocytosis: clinical and hybrid clinical-molecular models Animesh Pardanani, 1 Sahrish Shah, 1 Francesco Mannelli, 2 Yoseph C. Elala, 1 Paola Guglielmelli,
More informationPedro A. Martinez, PhD December 7 th, 2015
RAP-536 (Murine ACE-536/Luspatercept) Inhibits Smad2/3 Signaling and Promotes Erythroid Differentiation By Restoring GATA-1 Function in Murine β-thalassemia Pedro A. Martinez, PhD December 7 th, 2015 Outline
More informationEditorial Process: Submission:11/21/2017 Acceptance:06/19/2018
DOI:10.22034/APJCP.2018.19.7.1825 RESEARCH ARTICLE Editorial Process: Submission:11/21/2017 Acceptance:06/19/2018 The Frequency of SF3B1 Mutations in Thai Patients with Myelodysplastic Syndrome Punchita
More informationLENALIDOMIDA EN EL SMD 5Q-
LENALIDOMIDA EN EL SMD 5Q- EXPERIENCIA ESPAÑOLA 37 Diada Internacional 7 de Junio de 2013 M. Díez Campelo Hematología HOSPITAL UNIVERSITARIO 15-30% MDS Introduction Sole anomaly or in addition to 1 cytogenetics
More informationThe Evolving Role of Transplantation for MPN
The Evolving Role of Transplantation for MPN (PMF, PV, ET) H.Joachim Deeg MD Fred Hutchinson Cancer Research Center, University of Washington, Seattle WA, SCCA jdeeg@fhcrc.org 10 th J. Niblack Conference
More informationAgonistes du récepteur de la thrombopoïétine dans les SMD et AA
Agonistes du récepteur de la thrombopoïétine dans les SMD et AA Pr. Aristoteles Giagounidis Klinik für Onkologie, Hämatologie und Palliativmedizin Marien Hospital Düsseldorf Rochusstr. 2, D 40479 Düsseldorf
More informationShould Mutation Status in PMF Guide Therapy? No! Brady L. Stein, MD MHS Assistant Professor of Medicine Division of Hematology/Oncology
Should Mutation Status in PMF Guide Therapy? No! Brady L. Stein, MD MHS Assistant Professor of Medicine Division of Hematology/Oncology Case presentation A 67 yo woman presents to transition care, as her
More informationIntroduction of an NGS gene panel into the Haemato-Oncology MPN service
Introduction of an NGS gene panel into the Haemato-Oncology MPN service Dr. Anna Skowronska, Dr Jane Bryon, Dr Samuel Clokie, Dr Yvonne Wallis and Professor Mike Griffiths West Midlands Regional Genetics
More informationSupplementary Appendix
Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Patel JP, Gönen M, Figueroa ME, et al. Prognostic relevance
More informationWHO Update to Myeloproliferative Neoplasms
WHO Update to Myeloproliferative Neoplasms Archana M Agarwal, MD, Associate Professor of Pathology University of Utah Department of Pathology/ARUP Laboratories Myeloproliferative Neoplasms The categories
More informationCorporate Presentation January John Scarlett, M.D., President & CEO Olivia Bloom, EVP Finance & CFO Anna Krassowska, Ph.D., Investor Relations
Corporate Presentation January 2018 John Scarlett, M.D., President & CEO Olivia Bloom, EVP Finance & CFO Anna Krassowska, Ph.D., Investor Relations Forward-Looking Statements Except for the historical
More informationGuidelines for the diagnosis and treatment of Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia. Nordic MDS Group
Guidelines for the diagnosis and treatment of Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia Nordic MDS Group 8th update, May 2017 1 WRITING COMMITTEE... 4 CONTACT INFORMATION... 4 EVIDENCE
More informationIPSS Modified 7/27/2011. WHO-Based Prognostic Scoring System (WPSS)
Advances in MDS Treatment: What s on the Horizon? New Prognostic Models and Therapies Jason Gotlib, MD, MS Assistant Professor of Medicine (Hematology) Stanford Cancer Center AA&MDSIF July 3, 011 WHO-Based
More information2/7/2017. Updates in MDS: Overview
Updates in Myelodysplastic Syndromes Mikkael A. Sekeres, MD, MS Professor of Medicine Vice-chair for Clinical Research Director, Leukemia Program @MikkaelSekeres Updates in MDS: Overview GENOMICS: Mutational
More informationMDS-004 Study: REVLIMID (lenalidomide) versus Placebo in Myelodysplastic Syndromes with Deletion (5q) Abnormality
MDS-4 Study: REVLIMID (lenalidomide) versus Placebo in Myelodysplastic Syndromes with Deletion (5q) Abnormality TABLE OF CONTENTS Section 1. Executive Summary Section 2. Background Section
More informationPrognostic models in myelodysplastic syndromes
MYELODYSPLASTIC SYNDROMES:WHAT MAKES THERAPY EFFECTIVE? Prognostic models in myelodysplastic syndromes Rafael Bejar 1 1 Moores Cancer Center, Division of Hematology and Oncology, University of California,
More information