An international consortium proposal of uniform response criteria for myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in adults.

Myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) are hematologically diverse stem cell malignancies sharing phenotypic features of both myelodysplastic syndromes and myeloproliferative neoplasms. There are currently no standard treatment recommendations for most adult patients with MDS/MPN. To optimize efforts to improve the management and disease outcomes, it is essential to identify meaningful clinical and biologic end points and standardized response criteria for clinical trials. The dual dysplastic and proliferative features in these stem cell malignancies define their uniqueness and challenges. We propose response assessment guidelines to harmonize future clinical trials with the principal objective of establishing suitable treatment algorithms. An international panel comprising laboratory and clinical experts in MDS/MPN was established involving 3 independent academic MDS/MPN workshops (March 2013, December 2013, and June 2014). These recommendations are the result of this collaborative project sponsored by the MDS Foundation.

[1]  G. Mufti,et al.  An International MDS/MPN Working Group’s perspective and recommendations on molecular pathogenesis, diagnosis and clinical characterization of myelodysplastic/myeloproliferative neoplasms , 2015, Haematologica.

[2]  M. Loh,et al.  Criteria for evaluating response and outcome in clinical trials for children with juvenile myelomonocytic leukemia , 2015, Haematologica.

[3]  M. Savona Are we altering the natural history of primary myelofibrosis? , 2014, Leukemia research.

[4]  P. Campbell,et al.  Driver somatic mutations identify distinct disease entities within myeloid neoplasms with myelodysplasia. , 2014, Blood.

[5]  F. Stingo,et al.  Atypical chronic myeloid leukemia is clinically distinct from unclassifiable myelodysplastic/myeloproliferative neoplasms. , 2014, Blood.

[6]  A. Kohlmann,et al.  RARS-T Patients Harbor SF3B1 Mutations In 90.2% and Can Be Characterized By Mutations In ASXL1 and Other Spliceosome Genes In Most Of The Remaining Cases , 2013 .

[7]  R. Laborde,et al.  Mayo prognostic model for WHO-defined chronic myelomonocytic leukemia: ASXL1 and spliceosome component mutations and outcomes , 2013, Leukemia.

[8]  T. George,et al.  The new genetics of chronic neutrophilic leukemia and atypical CML: implications for diagnosis and treatment. , 2013, Blood.

[9]  G. Leone,et al.  Management recommendations for chronic myelomonocytic leukemia: consensus statements from the SIE, SIES, GITMO groups , 2013, Haematologica.

[10]  Francisco Cervantes,et al.  Revised response criteria for myelofibrosis: International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus report. , 2013, Blood.

[11]  S. Miyano,et al.  Exome sequencing identifies secondary mutations of SETBP1 and JAK3 in juvenile myelomonocytic leukemia , 2013, Nature Genetics.

[12]  S. Miyano,et al.  Somatic SETBP1 mutations in myeloid malignancies , 2013, Nature Genetics.

[13]  D. Birnbaum,et al.  Prognostic score including gene mutations in chronic myelomonocytic leukemia. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  H. Kantarjian,et al.  Exploratory analysis of the effect of ruxolitinib on bone marrow morphology in patients with myelofibrosis. , 2013 .

[15]  Angela G. Fleischman,et al.  Oncogenic CSF3R mutations in chronic neutrophilic leukemia and atypical CML. , 2013, The New England journal of medicine.

[16]  M. Rozman,et al.  Age, JAK2V617F and SF3B1 mutations are the main predicting factors for survival in refractory anaemia with ring sideroblasts and marked thrombocytosis , 2013, Leukemia.

[17]  L. Arenillas,et al.  Development and validation of a prognostic scoring system for patients with chronic myelomonocytic leukemia. , 2013, Blood.

[18]  A. Shields,et al.  Effect of ruxolitinib therapy on myelofibrosis-related symptoms and other patient-reported outcomes in COMFORT-I: a randomized, double-blind, placebo-controlled trial. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  E. Solary,et al.  Clonal architecture of chronic myelomonocytic leukemias. , 2013, Blood.

[20]  F. Fend,et al.  Development of monocytosis in patients with primary myelofibrosis indicates an accelerated phase of the disease , 2013, Modern Pathology.

[21]  A. Jankowska,et al.  Spliceosomal gene mutations are frequent events in the diverse mutational spectrum of chronic myelomonocytic leukemia but largely absent in juvenile myelomonocytic leukemia , 2013, Haematologica.

[22]  Roberta Spinelli,et al.  Recurrent SETBP1 mutations in atypical chronic myeloid leukemia , 2012, Nature Genetics.

[23]  M. Griesshammer,et al.  Myeloproliferative neoplasm (MPN) symptom assessment form total symptom score: prospective international assessment of an abbreviated symptom burden scoring system among patients with MPNs. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[24]  Y. Saunthararajah,et al.  A Prognostic Scoring System for Unclassifiable MDS and MDS/MPN , 2012 .

[25]  S. Ogawa,et al.  SRSF2 mutations in 275 cases with chronic myelomonocytic leukemia (CMML). , 2012, Blood.

[26]  Z. Estrov,et al.  Therapeutic effects of ruxolitinib in patients with myelofibrosis without clinically significant splenomegaly. , 2012, Blood.

[27]  Luca Malcovati,et al.  Revised international prognostic scoring system for myelodysplastic syndromes. , 2012, Blood.

[28]  A. Jankowska,et al.  A phase 2 trial of combination therapy with thalidomide, arsenic trioxide, dexamethasone, and ascorbic acid (TADA) in patients with overlap myelodysplastic/myeloproliferative neoplasms (MDS/MPN) or primary myelofibrosis (PMF) , 2012, Cancer.

[29]  M. Cazzola,et al.  Long-term outcomes of 107 patients with myelofibrosis receiving JAK1/JAK2 inhibitor ruxolitinib: survival advantage in comparison to matched historical controls. , 2012, Blood.

[30]  A. Jankowska,et al.  SF3B1, a splicing factor is frequently mutated in refractory anemia with ring sideroblasts , 2012, Leukemia.

[31]  Jason Gotlib,et al.  A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. , 2012, The New England journal of medicine.

[32]  Francisco Cervantes,et al.  JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. , 2012, The New England journal of medicine.

[33]  K. Döhner,et al.  Inactivation of polycomb repressive complex 2 components in myeloproliferative and myelodysplastic/myeloproliferative neoplasms. , 2012, Blood.

[34]  A. Jankowska,et al.  Mutational spectrum analysis of chronic myelomonocytic leukemia includes genes associated with epigenetic regulation: UTX, EZH2, and DNMT3A. , 2011, Blood.

[35]  A. Vekhoff,et al.  Molecular predictors of response to decitabine in advanced chronic myelomonocytic leukemia: a phase 2 trial. , 2011, Blood.

[36]  M. McDevitt,et al.  Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies. , 2011, Blood.

[37]  A. Tefferi,et al.  Circulating interleukin (IL)-8, IL-2R, IL-12, and IL-15 levels are independently prognostic in primary myelofibrosis: a comprehensive cytokine profiling study. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[38]  A. Jankowska,et al.  Novel homo- and hemizygous mutations in EZH2 in myeloid malignancies , 2010, Leukemia.

[39]  Ayalew Tefferi,et al.  Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. , 2010, The New England journal of medicine.

[40]  H. Drexler,et al.  Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders , 2010, Nature Genetics.

[41]  A. Jankowska,et al.  Spectrum of mutations in RARS-T patients includes TET2 and ASXL1 mutations. , 2010, Leukemia research.

[42]  A. Jankowska,et al.  Spectrum of molecular defects in juvenile myelomonocytic leukaemia includes ASXL1 mutations , 2010, British journal of haematology.

[43]  Ricardo Pasquini,et al.  Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. , 2010, The New England journal of medicine.

[44]  A. Jankowska,et al.  Mutations of an E3 ubiquitin ligase c-Cbl but not TET2 mutations are pathogenic in juvenile myelomonocytic leukemia. , 2010, Blood.

[45]  M. Gordon Dasatinib versus Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia , 2010 .

[46]  M. Gordon Nilotinib versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia , 2010 .

[47]  M. Loh,et al.  Mutations in CBL occur frequently in juvenile myelomonocytic leukemia. , 2009, Blood.

[48]  K. Foucar Myelodysplastic/myeloproliferative neoplasms. , 2009, American journal of clinical pathology.

[49]  C. Bloomfield,et al.  The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. , 2009, Blood.

[50]  Jungwon Huh,et al.  Loss of heterozygosity 4q24 and TET2 mutations associated with myelodysplastic/myeloproliferative neoplasms. , 2009, Blood.

[51]  Valeria Santini,et al.  Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. , 2009, The Lancet. Oncology.

[52]  J. Issa,et al.  Proposal for a new risk model in myelodysplastic syndrome that accounts for events not considered in the original International Prognostic Scoring System , 2008, Cancer.

[53]  U. Germing,et al.  The myelodysplastic/myeloproliferative neoplasms: myeloproliferative diseases with dysplastic features , 2008, Leukemia.

[54]  J. Sloan,et al.  Common troublesome symptoms and their impact on quality of life in patients with myelodysplastic syndromes (MDS): results of a large internet-based survey. , 2008, Leukemia research.

[55]  C. Niemeyer,et al.  Paediatric myelodysplastic syndromes and juvenile myelomonocytic leukaemia: molecular classification and treatment options , 2008, British journal of haematology.

[56]  D. Dingli,et al.  Monocytosis is an adverse prognostic factor for survival in younger patients with primary myelofibrosis. , 2007, Leukemia research.

[57]  J. Maciejewski,et al.  Refractory anemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T), another myeloproliferative condition characterized by JAK2 V617F mutation. , 2006, Blood.

[58]  H. Deeg,et al.  International Working Group (IWG) consensus criteria for treatment response in myelofibrosis with myeloid metaplasia, for the IWG for Myelofibrosis Research and Treatment (IWG-MRT). , 2006, Blood.

[59]  B. Cheson,et al.  Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. , 2006, Blood.

[60]  M. Loh,et al.  Inherited predispositions and hyperactive Ras in myeloid leukemogenesis , 2006, Pediatric blood & cancer.

[61]  J. D. van der Walt,et al.  European consensus on grading bone marrow fibrosis and assessment of cellularity. , 2005, Haematologica.

[62]  U. Germing,et al.  Risk Assessment in Chronic Myelomonocytic Leukemia (CMML) , 2004, Leukemia & lymphoma.

[63]  J. Bueno,et al.  Two groups of chronic myelomonocytic leukaemia: myelodysplastic and myeloproliferative. Prognostic implications in a series of a single center. , 2002, Leukemia research.

[64]  Terry L. Smith,et al.  Prognostic factors and scoring systems in chronic myelomonocytic leukemia: a retrospective analysis of 213 patients. , 2002, Blood.

[65]  Michael A. Patton,et al.  Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome , 2001, Nature Genetics.

[66]  C. Sawyers,et al.  Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. , 2001, The New England journal of medicine.

[67]  U. Germing,et al.  Problems in the classification of CMML--dysplastic versus proliferative type. , 1998, Leukemia research.

[68]  T Hamblin,et al.  International scoring system for evaluating prognosis in myelodysplastic syndromes. , 1997, Blood.

[69]  V. Rich Personal communication , 1989, Nature.