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

EUMDS Registry Participants; Alexandra Gwen Smith; Ge Yu

doi:10.3324/haematol.2018.212217

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

EUMDS Registry Participants, Alexandra Gwen Smith, Ge Yu

Health Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

Progression-free survival of lower-risk myelodysplastic syndromes patients 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 of newly diagnosed lower-risk myelodysplastic syndromes patients from 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 myelodysplastic syndromes /acute myeloid leukemia as events. Of the 1267 patients included in the analyses, 317 patients died without progression, in 162 patients the disease had progressed. Progression-free survival was significantly associated with age, EQ-5D index, baseline WHO classification, bone marrow blast count, cytogenetic risk category, number of cytopenias, and country. Transfusion dose density was inversely associated with progression-free survival (p<1x10-4): 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 erythropoietin agents, lenalidomide and/or iron chelators. Conclusion: the negative effect of transfusion treatment on progression-free survival 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 progression-free survival. This trial was registered at www.clinicaltrials.gov as #NCT00600860.

Original language	English
Pages (from-to)	632-639
Number of pages	8
Journal	Haematologica-The hematology journal
Volume	105
Issue number	3
Early online date	6 Jun 2019
DOIs	https://doi.org/10.3324/haematol.2018.212217
Publication status	E-pub ahead of print - 6 Jun 2019

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@article{5acbf777da8e42d2a61ceb83fcc0edba,

title = "Impact of red blood cell transfusion dose density on progression-free survival in lower-risk myelodysplastic syndromes patients",

abstract = "Progression-free survival of lower-risk myelodysplastic syndromes patients 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 of newly diagnosed lower-risk myelodysplastic syndromes patients from 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 myelodysplastic syndromes /acute myeloid leukemia as events. Of the 1267 patients included in the analyses, 317 patients died without progression, in 162 patients the disease had progressed. Progression-free survival was significantly associated with age, EQ-5D index, baseline WHO classification, bone marrow blast count, cytogenetic risk category, number of cytopenias, and country. Transfusion dose density was inversely associated with progression-free survival (p<1x10-4): 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 erythropoietin agents, lenalidomide and/or iron chelators. Conclusion: the negative effect of transfusion treatment on progression-free survival 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 progression-free survival. This trial was registered at www.clinicaltrials.gov as #NCT00600860.",

author = "{EUMDS Registry Participants} and {de Swart}, Louise and Simon Crouch and Marlijn Hoeks and Saskia Langemeijer and Pierre Fenaux and Argiris Symeonidis and Jaroslav {\v C}erm{\'a}k and Eva Hellstr{\"o}m-Lindberg and Reinhard Stauder and Guillermo Sanz and Moshe Mittelman and Holm, {Mette Skov} and Luca Malcovati and Krzysztof M{\c a}dry and Ulrich Germing and Aurelia Tatic and Aleksandar Savic and Almeida, {Antonio Medina} and Njeto{\v c}ka Gredelj-{\v S}imec and Agnes Guerci-Bresler and Odile Beyne-Rauzy and Dominic Culligan and Ioannis Kotsianidis and Raphael Itzykson and {van Marrewijk}, Corine and Nicole Blijlevens and David Bowen and {de Witte}, Theo and Smith, {Alexandra Gwen} and Ge Yu",

note = "Copyright {\textcopyright} 2019, Ferrata Storti Foundation. ",

year = "2019",

month = jun,

day = "6",

doi = "10.3324/haematol.2018.212217",

language = "English",

volume = "105",

pages = "632--639",

journal = "Haematologica-The hematology journal",

issn = "0390-6078",

publisher = "Ferrata Storti Foundation",

number = "3",

}

TY - JOUR

T1 - Impact of red blood cell transfusion dose density on progression-free survival in lower-risk myelodysplastic syndromes patients

AU - EUMDS Registry Participants

AU - de Swart, Louise

AU - Crouch, Simon

AU - Hoeks, Marlijn

AU - Langemeijer, Saskia

AU - Fenaux, Pierre

AU - Symeonidis, Argiris

AU - Čermák, Jaroslav

AU - Hellström-Lindberg, Eva

AU - Stauder, Reinhard

AU - Sanz, Guillermo

AU - Mittelman, Moshe

AU - Holm, Mette Skov

AU - Malcovati, Luca

AU - Mądry, Krzysztof

AU - Germing, Ulrich

AU - Tatic, Aurelia

AU - Savic, Aleksandar

AU - Almeida, Antonio Medina

AU - Gredelj-Šimec, Njetočka

AU - Guerci-Bresler, Agnes

AU - Beyne-Rauzy, Odile

AU - Culligan, Dominic

AU - Kotsianidis, Ioannis

AU - Itzykson, Raphael

AU - van Marrewijk, Corine

AU - Blijlevens, Nicole

AU - Bowen, David

AU - de Witte, Theo

AU - Smith, Alexandra Gwen

AU - Yu, Ge

PY - 2019/6/6

Y1 - 2019/6/6

N2 - Progression-free survival of lower-risk myelodysplastic syndromes patients 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 of newly diagnosed lower-risk myelodysplastic syndromes patients from 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 myelodysplastic syndromes /acute myeloid leukemia as events. Of the 1267 patients included in the analyses, 317 patients died without progression, in 162 patients the disease had progressed. Progression-free survival was significantly associated with age, EQ-5D index, baseline WHO classification, bone marrow blast count, cytogenetic risk category, number of cytopenias, and country. Transfusion dose density was inversely associated with progression-free survival (p<1x10-4): 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 erythropoietin agents, lenalidomide and/or iron chelators. Conclusion: the negative effect of transfusion treatment on progression-free survival 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 progression-free survival. This trial was registered at www.clinicaltrials.gov as #NCT00600860.

AB - Progression-free survival of lower-risk myelodysplastic syndromes patients 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 of newly diagnosed lower-risk myelodysplastic syndromes patients from 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 myelodysplastic syndromes /acute myeloid leukemia as events. Of the 1267 patients included in the analyses, 317 patients died without progression, in 162 patients the disease had progressed. Progression-free survival was significantly associated with age, EQ-5D index, baseline WHO classification, bone marrow blast count, cytogenetic risk category, number of cytopenias, and country. Transfusion dose density was inversely associated with progression-free survival (p<1x10-4): 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 erythropoietin agents, lenalidomide and/or iron chelators. Conclusion: the negative effect of transfusion treatment on progression-free survival 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 progression-free survival. This trial was registered at www.clinicaltrials.gov as #NCT00600860.

U2 - 10.3324/haematol.2018.212217

DO - 10.3324/haematol.2018.212217

M3 - Article

C2 - 31171638

SN - 0390-6078

VL - 105

SP - 632

EP - 639

JO - Haematologica-The hematology journal

JF - Haematologica-The hematology journal

IS - 3

ER -