Myelodysplastic syndrome

Decision analysis of allogeneic hematopoietic stem cell transplantation for patients with myelodysplastic syndrome stratified according to the revised International Prognostic Scoring System

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Allogeneic hematopoietic stem cell transplantation (allo-SCT) represents the only curative treatment for patients with myelodysplastic syndrome (MDS), but involves non-negligible morbidity and mortality. Crucial questions in clinical decision-making include the definition of optimal timing of the procedure and the benefit of cytoreduction before transplant in high-risk patients. We carried out a decision analysis on 1728 MDS who received supportive care, transplantation or hypomethylating agents (HMAs). Risk assessment was based on the revised International Prognostic Scoring System (IPSS-R). We used a continuous-time multistate Markov model to describe the natural history of disease and evaluate the effect of different treatment policies on survival. Life expectancy increased when transplantation was delayed from the initial stages to intermediate IPSS-R risk (gain-of-life expectancy 5.3, 4.7 and 2.8 years for patients aged 55, 60 and 65 years, respectively), and then decreased for higher risks. Modeling decision analysis on IPSS-R versus original IPSS changed transplantation policy in 29% of patients, resulting in a 2-year gain in life expectancy. In advanced stages, HMAs given before transplant is associated with a 2-year gain-of-life expectancy, especially in older patients. These results provide a preliminary evidence to maximize the effectiveness of allo-SCT in MDS.

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The study was supported by AIRC (Associazione Italiana Per la Ricerca sul Cancro, IG_17554), Milan; Fondazione Veronesi, Milan, Fondazione Cariplo and Regione Lombardia, Milan (Grant ID 42916996); Beat Leukemia Foundation, Milan, Fondazione Banca del Monte di Lombardia, Pavia, Italy; Worldwide Cancer Research (Grant 15-1226), St Andrews – UK to MGDP; by UK Medical Research Council (Grant code U105260566) to CHJ; and by AIRC, Milan, Italy (Special Program Molecular Clinical Oncology 5x1000, project 1005) to MC.

Author contributions

MGDP, CHJ, MC and AR designed, performed and coordinated the research, collected, contributed, analyzed and interpreted the data, and wrote the manuscript; CHJ and CP performed the statistical analyses, produced the figures and edited the manuscript; EPA, MR, AB, MTvL, MB, BA, AB, SG, VS, LM, MU, CM, ET, MTV, PM, FO, API, RC, GG, AM, PP, LB, EA, EO, SS, VF, AS and FB collected and contributed data and critically reviewed the manuscript.

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Correspondence to M G Della Porta.

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The authors declare no conflict of interest.

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