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. 2023 Jul 1;108(7):1900-1908.
doi: 10.3324/haematol.2022.281958.

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

Guru Subramanian Guru Murthy  1 , Soyoung Kim  2 , Noel Estrada-Merly  3 , Muhammad Bilal Abid  4 , Mahmoud Aljurf  5 , Amer Assal  6 , Talha Badar  7 , Sherif M Badawy  8 , Karen Ballen  9 , Amer Beitinjaneh  10 , Jan Cerny  11 , Saurabh Chhabra  3 , Zachariah DeFilipp  12 , Bhagirathbhai Dholaria  13 , Miguel Angel Diaz Perez  14 , Shatha Farhan  15 , Cesar O Freytes  16 , Robert Peter Gale  17 , Siddhartha Ganguly  18 , Vikas Gupta  19 , Michael R Grunwald  20 , Nada Hamad  21 , Gerhard C Hildebrandt  22 , Yoshihiro Inamoto  23 , Tania Jain  24 , Omer Jamy  25 , Mark Juckett  26 , Matt Kalaycio  27 , Maxwell M Krem  28 , Hillard M Lazarus  29 , Mark Litzow  30 , Reinhold Munker  22 , Hemant S Murthy  31 , Sunita Nathan  32 , Taiga Nishihori  33 , Guillermo Ortí  34 , Sagar S Patel  35 , Marjolein Van der Poel  36 , David A Rizzieri  37 , Bipin N Savani  38 , Sachiko Seo  39 , Melhem Solh  40 , Leo F Verdonck  41 , Baldeep Wirk  42 , Jean A Yared  43 , Ryotaro Nakamura  44 , Betul Oran  45 , Bart Scott  46 , Wael Saber  3
Affiliations

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

Guru Subramanian Guru Murthy et al. Haematologica. .

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.

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Figures

Figure 1.
Figure 1.
Overall survival with reduced-intensity conditioning. RIC: reduced-intensity conditioning; Flu: fludarabine; Bu: busulfan; Mel: melphalan.
Figure 2.
Figure 2.
Overall survival with myeloablative conditioning. MAC: myeloablative conditioning; Flu: fludarabine; Bu: busul-fan; Mel: melphalan.
Figure 3.
Figure 3.
Graf-versus-host-disease-free relapse-free survival with myeloablative conditioning. MAC: myeloablative conditioning; CY: cyclophosphamide; GvHD: graft-versus-host disease; Flu: fludarabine; Bu: busulfan; Mel: melphalan.
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