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Association between the choice of the conditioning regimen and outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis. Haematologica 2023 Jul 01;108(7):1900-1908

Date

02/14/2023

Pubmed ID

36779595

Pubmed Central ID

PMC10316233

DOI

10.3324/haematol.2022.281958

Scopus ID

2-s2.0-85152676494 (requires institutional sign-in at Scopus site)   11 Citations

Abstract

Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative treatment for myelofibrosis. However, the optimal conditioning regimen either with reduced-intensity conditioning (RIC) or myeloablative conditioning (MAC) is not well known. Using the Center for International Blood and Marrow Transplant Research database, we identified adults aged ≥18 years with myelofibrosis undergoing allo-HCT between 2008-2019 and analyzed the outcomes separately in the RIC and MAC cohorts based on the conditioning regimens used. Among 872 eligible patients, 493 underwent allo-HCT using RIC (fludarabine/ busulfan n=166, fludarabine/melphalan n=327) and 379 using MAC (fludarabine/busulfan n=247, busulfan/cyclophosphamide n=132). In multivariable analysis with RIC, fludarabine/melphalan was associated with inferior overall survival (hazard ratio [HR]=1.80; 95% confidenec interval [CI]: 1.15-2.81; P=0.009), higher early non-relapse mortality (HR=1.81; 95% CI: 1.12-2.91; P=0.01) and higher acute graft-versus-host disease (GvHD) (grade 2-4 HR=1.45; 95% CI: 1.03-2.03; P=0.03; grade 3-4 HR=2.21; 95%CI: 1.28-3.83; P=0.004) compared to fludarabine/busulfan. In the MAC setting, busulfan/cyclophosphamide was associated with a higher acute GvHD (grade 2-4 HR=2.33; 95% CI: 1.67-3.25; P<0.001; grade 3-4 HR=2.31; 95% CI: 1.52-3.52; P<0.001) and inferior GvHD-free relapse-free survival (GRFS) (HR=1.94; 95% CI: 1.49-2.53; P<0.001) as compared to fludarabine/busulfan. Hence, our study suggests that fludarabine/busulfan is associated with better outcomes in RIC (better overall survival, lower early non-relapse mortality, lower acute GvHD) and MAC (lower acute GvHD and better GRFS) in myelofibrosis.

Author List

Murthy GSG, Kim S, Estrada-Merly N, Abid MB, Aljurf M, Assal A, Badar T, Badawy SM, Ballen K, Beitinjaneh A, Cerny J, Chhabra S, DeFilipp Z, Dholaria B, Perez MAD, Farhan S, Freytes CO, Gale RP, Ganguly S, Gupta V, Grunwald MR, Hamad N, Hildebrandt GC, Inamoto Y, Jain T, Jamy O, Juckett M, Kalaycio M, Krem MM, Lazarus HM, Litzow M, Munker R, Murthy HS, Nathan S, Nishihori T, Ortí G, Patel SS, Van der Poel M, Rizzieri DA, Savani BN, Seo S, Solh M, Verdonck LF, Wirk B, Yared JA, Nakamura R, Oran B, Scott B, Saber W

Authors

Soyoung Kim PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin
Wael Saber MD, MS Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Busulfan
Cyclophosphamide
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Humans
Melphalan
Primary Myelofibrosis
Retrospective Studies
Transplantation Conditioning
Vidarabine