Early platelet count kinetics has prognostic value in lower-risk myelodysplastic syndromes
Raphael Itzykson, Simon Crouch, Erica Travaglino, Alex Smith, Argiris Symeonidis, Eva Hellström-Lindberg, Guillermo Sanz, Jaroslav Čermák, Reinhard Stauder, Chiara Elena, Ulrich Germing, Moshe Mittelman, Saskia Langemeijer, Krzysztof Mądry, Aurelia Tatic, Mette Skov Holm, Antonio Medina Almeida, Aleksandar Savic, Njetočka Gredelj Šimec, Elisa Luño, Dominic Culligan, Agnes Guerci-Bresler, Luca Malcovati, Corine van Marrewijk, David Bowen, Theo de Witte, Pierre Fenaux, European MDS Registry members, Raphael Itzykson, Simon Crouch, Erica Travaglino, Alex Smith, Argiris Symeonidis, Eva Hellström-Lindberg, Guillermo Sanz, Jaroslav Čermák, Reinhard Stauder, Chiara Elena, Ulrich Germing, Moshe Mittelman, Saskia Langemeijer, Krzysztof Mądry, Aurelia Tatic, Mette Skov Holm, Antonio Medina Almeida, Aleksandar Savic, Njetočka Gredelj Šimec, Elisa Luño, Dominic Culligan, Agnes Guerci-Bresler, Luca Malcovati, Corine van Marrewijk, David Bowen, Theo de Witte, Pierre Fenaux, European MDS Registry members
Abstract
Prognosis of lower-risk (International Prognostic Scoring System [IPSS] low/intermediate-1) myelodysplastic syndrome (MDS) is heterogeneous and relies on steady-state assessment of cytopenias. We analyzed relative drops in neutrophil and platelet counts during the first 6 months of follow-up of lower-risk MDS patients. We performed a landmark analysis of overall survival (OS) of lower-risk MDS patients prospectively included in the European LeukaemiaNet MDS registry having a visit at 6 ± 1 month from inclusion to assess the prognostic relevance of relative drops in neutrophils and platelets, defined as (count at landmark - count at inclusion)/count at inclusion. Of 2102 patients, 807 were eligible for the stringent 6-month landmark analysis. Median age was 73 years. Revised IPSS was very low, low, and intermediate/higher in 26%, 43%, and 31% of patients, respectively. A relative drop in platelets >25% at landmark predicted shorter OS (5-year OS, 21.9% vs 48.6% with platelet drop ≤25%, P < 10-4), regardless of baseline IPSS-revised or absolute platelet counts. Relative neutrophil drop >25% had no significant impact on OS. We built a classifier based on red blood cell transfusion dependence (RBC-TD) and relative platelet drop >25% at landmark. Patients with none (62%), either (27%), or both criteria (11%) had 5-year OS of 53.3%, 32.7%, and 9.0%, respectively (P < 10-4). This classifier was validated in an independent cohort of 335 patients. Combining relative platelet drop >25% and RBC-TD at 6 months from diagnosis provides an inexpensive and noninvasive way to predict outcome in lower-risk MDS. This study was registered at www.clinicaltrials.gov as #NCT00600860.
Conflict of interest statement
Conflict-of-interest disclosure: R.I. has received research funding from Novartis and Janssen, honoraria from Celgene, BMS, and Sanofi, and consulting fees from Novartis, Otsuka, and Karyopharm. P.F. has received research funding from Amgen, Astex, Celgene, Janssen, and Novartis and honoraria from Janssen. A.M.A. has received honoraria from BMS and Alexion and consulting fees from Novartis, Celgene, and Servier. A. Symeonidis has received honoraria and consulting fees from Amgen, Celgene/GenesisPharma, Janssen-Cilag, Gilead, Pfizer, MSD, Novartis, and Genzyme/Sanofi. E.H.-L. has received research funding from Celgene. G.S. has received research funding and honoraria from Celgene, Novartis, Amgen, and consulting fees from Amgen, Boehringer-Ingelheim, Celgene, MSD, and Novartis. M.S.H. has received research funding Celgene. A. Savic has received honoraria and consulting fees from Pfizer, MSD, and Hoffmann-La Roche. U.G. has received research funding and honorarium from Novartis. C.v.M., project manager of the EUMDS Registry, is funded from the EUMDS project budget. T.d.W. has received research funding from Novartis, Celgene, and Amgen, and honorarium from Novartis as project coordinator EUMDS. The remaining authors declare no competing financial interests.
© 2018 by The American Society of Hematology.
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Source: PubMed