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Clinical Trial
. 2018 Aug 28;2(16):2079-2089.
doi: 10.1182/bloodadvances.2018020495.

Early platelet count kinetics has prognostic value in lower-risk myelodysplastic syndromes

Raphael Itzykson  1 , Simon Crouch  2 , Erica Travaglino  3 , Alex Smith  2 , Argiris Symeonidis  4 , Eva Hellström-Lindberg  5 , Guillermo Sanz  6   7 , Jaroslav Čermák  8 , Reinhard Stauder  9 , Chiara Elena  3 , Ulrich Germing  10 , Moshe Mittelman  11 , Saskia Langemeijer  12 , Krzysztof Mądry  13 , Aurelia Tatic  14 , Mette Skov Holm  15 , Antonio Medina Almeida  16 , Aleksandar Savic  17 , Njetočka Gredelj Šimec  18 , Elisa Luño  19 , Dominic Culligan  20 , Agnes Guerci-Bresler  21 , Luca Malcovati  3 , Corine van Marrewijk  12 , David Bowen  22 , Theo de Witte  23 , Pierre Fenaux; European MDS Registry members
Affiliations
Clinical Trial

Early platelet count kinetics has prognostic value in lower-risk myelodysplastic syndromes

Raphael Itzykson et al. Blood Adv. .

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.

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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.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Prognostic impact of relative drop in platelets and neutrophils. Kaplan-Meier plots of OS from landmark (with 95% CIs) according to 6-month relative platelet (A) and neutrophil (B) drop. CIP since landmark according to 6-month platelet (C) and neutrophil (D) drop. Blue, relative platelet or neutrophil drop ≤25%; red, relative platelet or neutrophil drop >25%.
Figure 2.
Figure 2.
Prognostic impact of relative platelet drop in defined subgroups. Forest plot of HRs of relative platelet drop >25% according to baseline IPSS-R risk and absolute platelet count at inclusion and landmark.
Figure 3.
Figure 3.
Design of the 6-month EUMDS classifier. Kaplan-Meier plots of OS (A) and CIP (B) from landmark according to the 6-month EUMDS classifier based on platelet drop >25% and RBC-TD at landmark. (C). Forest plots of HRs of each additional criterion in the 6-month EUMDS classifier according to baseline IPSS-R risk in the landmark cohort. Blue, no criteria; red, either criteria, green, both criteria.
Figure 4.
Figure 4.
Validation of the 6-month EUMDS classifier. Kaplan-Meier plots of OS in the external validation cohort (n = 335) according to platelet drop >25% at the 6-month landmark (blue, relative platelet drop ≤25%; red, relative platelet drop >25%) (A) and the 6-month EUMDS classifier (B). (C) CIP according to the 6-month EUMDS classifier. (B-C) Blue, no criteria; red, either criteria; green: both criteria.
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References

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