Haematologica (Feb 2023)

Association between the choice of the conditioning regimen and outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis

  • Guru Subramanian Guru Murthy,
  • Soyoung Kim,
  • Noel Estrada-Merly,
  • Muhammad Bilal Abid,
  • Mahmoud Aljurf,
  • Amer Assal,
  • Talha Badar,
  • Sherif M. Badawy,
  • Karen Ballen,
  • Amer Beitinjaneh,
  • Jan Cerny,
  • Saurabh Chhabra,
  • Zachariah DeFilipp,
  • Bhagirathbhai Dholaria,
  • Miguel Angel Diaz Perez,
  • Shatha Farhan,
  • Cesar O. Freytes,
  • Robert Peter Gale,
  • Siddhartha Ganguly,
  • Vikas Gupta,
  • Michael R. Grunwald,
  • Nada Hamad,
  • Gerhard C. Hildebrandt,
  • Yoshihiro Inamoto,
  • Tania Jain,
  • Omer Jamy,
  • Mark Juckett,
  • Matt Kalaycio,
  • Maxwell M. Krem,
  • Hillard M. Lazarus,
  • Mark Litzow,
  • Reinhold Munker,
  • Hemant S. Murthy,
  • Sunita Nathan,
  • Taiga Nishihori,
  • Guillermo Ortí,
  • Sagar S. Patel,
  • Marjolein van der Poel,
  • David A. Rizzieri,
  • Bipin N. Savani,
  • Sachiko Seo,
  • Melhem Solh,
  • Leo F. Verdonck,
  • Baldeep Wirk,
  • Jean A. Yared,
  • Ryotaro Nakamura,
  • Betul Oran,
  • Bart Scott,
  • Wael Saber

DOI
https://doi.org/10.3324/haematol.2022.281958
Journal volume & issue
Vol. 108, no. 7

Abstract

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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.