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
Affiliations
- Guru Subramanian Guru Murthy
- Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee
- Soyoung Kim
- Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, WI; CIBMTR® (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee
- Noel Estrada-Merly
- CIBMTR® (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee
- Muhammad Bilal Abid
- Divisions of Hematology/Oncology, and Infectious Diseases, Department of Medicine, Medical College of Wisconsin, Milwaukee
- Mahmoud Aljurf
- Department of Oncology, King Faisal Specialist Hospital Center and Research, Riyadh
- Amer Assal
- Columbia University Irving Medical Center, Department of Medicine, Bone Marrow Transplant and Cell Therapy Program
- Talha Badar
- Mayo Clinic, Jacksonville, FL
- Sherif M. Badawy
- Division of Hematology, Oncology and Stem Cell Transplantation, Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL; Department of Pediatrics, Northwestern University Feinberg School of Medicine
- Karen Ballen
- Division of Hematology/Oncology, University of Virginia Health System, Charlottesville, VA
- Amer Beitinjaneh
- Division of Transplantation and Cellular Therapy, University of Miami Hospital and Clinics, Slyvester Comprehensive Cancer Center, Miami, FL
- Jan Cerny
- Division of Hematology/Oncology, Department of Medicine, University of Massachusetts Medical Center, Worcester, MA
- Saurabh Chhabra
- CIBMTR® (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee
- Zachariah DeFilipp
- Hematopoietic Cell Transplant and Cellular Therapy Program, Massachusetts General Hospital
- Bhagirathbhai Dholaria
- Vanderbilt University Medical Center, Nashville, TN
- Miguel Angel Diaz Perez
- Department of Hematology/Oncology, Hospital Infantil Universitario Niño Jesus, Madrid
- Shatha Farhan
- Henry Ford Health System Stem Cell Transplant and Cellular Therapy Program, Detroit, MI
- Cesar O. Freytes
- University of Texas Health Science Center at San Antonio, San Antonio, TX
- Robert Peter Gale
- Haematology Research Centre, Department of Immunology and Inflammation, Imperial College London, London
- Siddhartha Ganguly
- Division of Hematological Malignancy and Cellular Therapeutics, University of Kansas Health System, Kansas City, KS
- Vikas Gupta
- MPN Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON
- Michael R. Grunwald
- Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Atrium Health, Charlotte, NC
- Nada Hamad
- St. Vincent Hospital, Darlinghurst, NSW
- Gerhard C. Hildebrandt
- Markey Cancer Center, University of Kentucky, Lexington, KY
- Yoshihiro Inamoto
- Division of Hematopoietic Stem Cell Transplantation, National Cancer Center, Tokyo
- Tania Jain
- John Hopkins University School of Medicine, Baltimore, MD
- Omer Jamy
- University of Alabama at Birmingham, Birmingham, AL
- Mark Juckett
- University of Minnesota Blood and Marrow Transplant Program – Adults
- Matt Kalaycio
- Cleveland Clinic Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH
- Maxwell M. Krem
- Kansas City VA Medical Center, Kansas City, MO
- Hillard M. Lazarus
- University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH
- Mark Litzow
- Division of Hematology and Transplant Center, Mayo Clinic Rochester, Rochester, MN
- Reinhold Munker
- Markey Cancer Center, University of Kentucky, Lexington, KY
- Hemant S. Murthy
- Division of Hematology-Oncology, Blood and Marrow Transplantation Program, Mayo Clinic, Jacksonville, FL
- Sunita Nathan
- Section of Bone Marrow Transplant and Cell Therapy, Rush University Medical Center
- Taiga Nishihori
- Department of Blood and Marrow Transplant and Cellular Immunotherapy (BMT CI), Moffitt Cancer Center, Tampa, FL
- Guillermo Ortí
- Vall d’Hebron University Hospital, Barcelona
- Sagar S. Patel
- Blood and Marrow Transplant Program, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT
- Marjolein van der Poel
- Department of Internal Medicine, Division of Hematology, GROW School for Oncology and Developmental Biology, Masstricht University Medical Center, Maastricht
- David A. Rizzieri
- Division of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, NC
- Bipin N. Savani
- Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
- Sachiko Seo
- Department of Hematology and Oncology, Dokkyo Medical University, Tochigo
- Melhem Solh
- The Blood and Marrow Transplant Group of Georgia, Northside Hospital, Atlanta, GA
- Leo F. Verdonck
- Department of Hematology/Oncology, Isala, Clinic, Zwolle
- Baldeep Wirk
- Bone Marrow Transplant Program, Penn State Cancer Institute, Hershey, Pennsylvania
- Jean A. Yared
- Transplantation and Cellular Therapy Program, Division of Hematology/Oncology, Department of Medicine, Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD
- Ryotaro Nakamura
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA
- Betul Oran
- Department of Stem Cell Transplantation, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
- Bart Scott
- Fred Hutchinson Cancer Research Center, Seattle, WA
- Wael Saber
- CIBMTR® (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee
- DOI
- https://doi.org/10.3324/haematol.2022.281958
- Journal volume & issue
-
Vol. 108,
no. 7
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.
