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Impact of red blood cell transfusion dose density on progression-free survival in patients with lower-risk myelodysplastic syndromes.

ABSTRACT: Progression-free survival (PFS) of patients with lower-risk myelodysplastic syndromes (MDS) treated with red blood cell transfusions is usually reduced, but it is unclear whether transfusion dose density is an independent prognostic factor. The European MDS Registry collects prospective data at 6-monthly intervals from newly diagnosed lower-risk myelodysplastic syndromes patients in 16 European countries and Israel. Data on the transfusion dose density - the cumulative dose received at the end of each interval divided by the time since the beginning of the interval in which the first transfusion was received - were analyzed using proportional hazards regression with time-varying co-variates, with death and progression to higher-risk MDS/acute myeloid leukemia as events. Of the 1,267 patients included in the analyses, 317 died without progression; in 162 patients the disease had progressed. PFS was significantly associated with age, EQ-5D index, baseline World Health Organization classification, bone marrow blast count, cytogenetic risk category, number of cytopenias, and country. Transfusion dose density was inversely associated with PFS (P<1×10-4): dose density had an increasing effect on hazard until a dose density of 3 units/16 weeks. The transfusion dose density effect continued to increase beyond 8 units/16 weeks after correction for the impact of treatment with erythropoiesis-stimulating agents, lenalidomide and/or iron chelators. In conclusion, the negative effect of transfusion treatment on PFS already occurs at transfusion densities below 3 units/16 weeks. This indicates that transfusion dependency, even at relatively low dose densities, may be considered as an indicator of inferior PFS. This trial was registered at www.clinicaltrials.gov as #NCT00600860.

SUBMITTER: de Swart L

PROVIDER: S-EPMC7049377 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Impact of red blood cell transfusion dose density on progression-free survival in patients with lower-risk myelodysplastic syndromes.

de Swart Louise L Crouch Simon S Hoeks Marlijn M Smith Alex A Langemeijer Saskia S Fenaux Pierre P Symeonidis Argiris A Cermâk Jaroslav J Hellström-Lindberg Eva E Stauder Reinhard R Sanz Guillermo G Mittelman Moshe M Holm Mette Skov MS Malcovati Luca L Mądry Krzysztof K Germing Ulrich U Tatic Aurelia A Savic Aleksandar A Almeida Antonio Medina AM Gredelj-Simec Njetocka N Guerci-Bresler Agnes A Beyne-Rauzy Odile O Culligan Dominic D Kotsianidis Ioannis I Itzykson Raphael R van Marrewijk Corine C Blijlevens Nicole N Bowen David D de Witte Theo T

Haematologica 20190606 3

Progression-free survival (PFS) of patients with lower-risk myelodysplastic syndromes (MDS) treated with red blood cell transfusions is usually reduced, but it is unclear whether transfusion dose density is an independent prognostic factor. The European MDS Registry collects prospective data at 6-monthly intervals from newly diagnosed lower-risk myelodysplastic syndromes patients in 16 European countries and Israel. Data on the transfusion dose density - the cumulative dose received at the end o ...[more]

PMID: 31171638

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Project description:Red blood cell transfusions remain one of the cornerstones in supportive care of lower-risk patients with myelodysplastic syndromes. We hypothesized that patients develop oxidant-mediated tissue injury through the formation of toxic iron species, caused either by red blood cell transfusions or by ineffective erythropoiesis. We analyzed serum samples from 100 lower-risk patients with myelodysplastic syndromes at six-month intervals for transferrin saturation, hepcidin-25, growth differentiation factor 15, soluble transferrin receptor, non-transferrin bound iron and labile plasma iron in order to evaluate temporal changes in iron metabolism and the presence of potentially toxic iron species and their impact on survival. Hepcidin levels were low in 34 patients with ringed sideroblasts compared to 66 patients without. Increases of hepcidin and non-transferrin bound iron levels were visible early in follow-up of all transfusion-dependent patient groups. Hepcidin levels significantly decreased over time in transfusion-independent patients with ringed sideroblasts. Increased soluble transferrin receptor levels in transfusion-independent patients with ringed sideroblasts confirmed the presence of ineffective erythropoiesis and suppression of hepcidin production in these patients. Detectable labile plasma iron levels in combination with high transferrin saturation levels occurred almost exclusively in patients with ringed sideroblasts and all transfusion-dependent patient groups. Detectable labile plasma iron levels in transfusion-dependent patients without ringed sideroblasts were associated with decreased survival. In conclusion, toxic iron species occurred in all transfusion-dependent patients and in transfusion-independent patients with ringed sideroblasts. Labile plasma iron appeared to be a clinically relevant measure for potential iron toxicity and a prognostic factor for survival in transfusion-dependent patients. clinicaltrials.gov Identifier: 00600860.

Dataset Information

Impact of red blood cell transfusion dose density on progression-free survival in patients with lower-risk myelodysplastic syndromes.

Publications

Impact of red blood cell transfusion dose density on progression-free survival in patients with lower-risk myelodysplastic syndromes.

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