Impact of Red Blood Cell Transfusion Intensity on Progression-Free Survival in Lower-Risk MDS Patients Included in the European Leukemianet MDS Registry

Abstract

Abstract Background Progression-free survival (PFS) of lower-risk (LR) MDS patients treated with red blood cell transfusions (RBCT) is usually reduced, but whether the RBCT intensity is important for prognosis is unknown. The EUMDS Registry contains data on 2,192 newly diagnosed LR-MDS patients from 16 European countries and Israel, collected at diagnosis and at 6 months intervals.The aim of this analysis is to assess the effect of RBCT intensity on PFS of patients with LR-MDS in a prospective, observational setting. MethodsData on the number of RBCT units received during each visit-interval were analyzed using proportional hazards regression with time-varying co-variates. The cumulative dose received at the end of each interval was divided by the time since the beginning of the interval in which the first RBCT was received rather than for each visit-interval, to give an overall dose density. Dose density rises over time when RBCT intensity increases over time, but declines when patient becomes RBCT independent after treatment. In Cox regression with time-varying covariates, PFS was adjusted by relevant confounders, including age, gender, patient condition (proxied by EQ-5D index), and number of cytopenias at diagnosis. We analyzed a cohort of 1,509 patients with at least 3 visit reports available. Within this group 476 patients have died and 118 patients have progressed to higher-risk MDS or AML, which were defined as events. ResultsPatients with ring sideroblastic MDS (RS-MDS) received more frequently RBCT after diagnosis compared to non-RS-MDS (60% vs 54%). Very low-risk patients according to IPSS-R received RBCT less often compared to intermediate risk patients (35% vs 69%). Age, gender, presence of co-morbidities, and countries influenced RBCT dependency and RBCT rate. The transfused patients were subdivided in 3 groups according to the maximum RBCT rate over time: low rate ( 2 units/month) in order to analyse the impact of the RBCT rate in more detail (figure A). Unadjusted overall PFS stratified this way, is shown in figure B. Univariate analysis of the 404 patients transfused at a high rate showed a strong association of age (p ConclusionThe negative effect of RBCT treatment on PFS already occurs at low RBCT densities below 2 units/month and before 25 units of RBCT have been transfused. This indicates that the RBCT dependency, even at relatively low intensities, may be considered as an indicator of poor prognosis for survival. Download : Download high-res image (93KB) Download : Download full-size image Figure . Disclosures Fenaux: Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Astex: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Astex: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Sanz: Gamida Cell: Research Funding. Germing: Janssen: Honoraria; Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Almeida: Servier: Consultancy; Alexion: Honoraria; Novartis: Consultancy; Celgene: Consultancy; Bristol Meyer Squibb: Honoraria. Itzykson: Janssen: Research Funding; Novartis: Research Funding. Park: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Hospira/Pfizer: Research Funding; Celgene: Research Funding. de Witte: Novartis: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Janssen Cilag: Research Funding.