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Donor body mass index does not predict graft versus host disease following hematopoietic cell transplantation

Bone Marrow Transplantation volume 53, pages 932–937 (2018)Cite this article

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Graft versus host disease (GVHD) is a serious complication affecting nearly half of hematopoietic cell transplantation (HCT) recipients [1]. It is characterized by lymphocyte activation and proliferation, a surge in pro-inflammatory cytokines and tissue destruction [2]. GVHD risk factors include degree of donor-recipient human leukocyte antigen (HLA) mismatch, stem cell source, donor-recipient sex matching, donor age, and pre-HCT conditioning regimen intensity [3, 4]. More than one-third of HCT donors are obese, and although previous studies have demonstrated either no or minimal effect of recipient body mass index (BMI) on transplant outcomes [5,6,7,8], the impact of donor obesity and donor inflammation on recipient outcomes have not been investigated. Obesity, defined as a BMI ≥ 30 kg/m2, and overweight (BMI 25–29.9 kg/m2), are chronic inflammatory states. Most individuals with obesity have increased numbers of circulating monocytes secreting pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6 [9], similar to the inflammation and cytokine dysregulation that are observed in GVHD [2].We sought to address the hypothesis that stem cell products from obese donors would result in engrafted hematopoietic cells that are more inflammatory, resulting in increased rates of acute (aGVHD) and chronic GVHD (cGVHD) in transplant recipients.

Data were obtained from the Center for International Blood and Marrow Transplantation Research (CIBMTR). The CIBMTR is a collaboration between the Medical College of Wisconsin and the National Marrow Donor Program/Be the Match. Individuals included in the study had a primary diagnosis of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), or myelodysplastic syndrome (MDS), and underwent their first allogeneic HLA-A, B, C and DRB1-matched (8/8 matched) unrelated peripheral blood stem cell (PBSC) transplant between 2000 to 2013. Individuals who received ex vivo T-cell depleted or CD34+ selected grafts, transplants from multiple donors, or who had missing donor data were excluded from the analysis. Primary endpoints included incidence of grade II–IV and grade III–IV aGVHD and cGVHD. aGVHD II-IV was graded according to consensus criteria at day 100 with death without aGVHD as a competing risk. cGVHD was reported as cumulative incidence at 6 months, 1 and 2 years post-HCT with death without cGVHD as a competing risk. Secondary outcomes included relapse, disease free survival (DFS), non-relapse mortality (NRM), and overall survival (OS). Relapse was reported as a cumulative incidence with NRM as a competing risk. DFS was defined as time to treatment failure either death or relapse. NRM was defined as death in continuous remission with relapse as a competing risk. Donor BMI category definitions included: underweight (BMI < 18.5 kg/m2), normal weight (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2), obese (30–39.9 kg/m2) and morbidly obese (≥40 kg/m2). Other patient-related, disease-related, and transplant-related variables considered included recipient and donor age at HCT, recipient and donor race, donor-recipient sex match, donor and recipient cytomegalovirus (CMV) status, recipient Karnofsky score prior to HCT, disease status at HCT, interval from diagnosis to HCT, HCT conditioning intensity, use of total body irradiation (TBI) in conditioning, CD34+ cell dose, GVHD prophylaxis and use of anti-thymocyte globulin (ATG) or alemtuzumab.

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Acknowledgements

This work was funded in part by the Children’s Cancer Research Fund, Minneapolis, MN (LMT) and the National Center for Advancing Translational Sciences (National Institutes of Health (NIH)) through Grant Numbers UL1TR001436 and KL2TR001438 (JMK). The CIBMTR is supported primarily by Public Health Service Grant/Cooperative Agreement 5U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 4U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-17-1-2388 and N0014-17-1-2850 from the Office of Naval Research; and grants from *Actinium Pharmaceuticals, Inc.; *Amgen, Inc.; *Amneal Biosciences; *Angiocrine Bioscience, Inc.; Anonymous donation to the Medical College of Wisconsin; Astellas Pharma US; Atara Biotherapeutics, Inc.; Be the Match Foundation; *bluebird bio, Inc.; *Bristol Myers Squibb Oncology; *Celgene Corporation; Cerus Corporation; *Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Gamida Cell Ltd.; Gilead Sciences, Inc.; HistoGenetics, Inc.; Immucor; *Incyte Corporation; Janssen Scientific Affairs, LLC; *Jazz Pharmaceuticals, Inc.; Juno Therapeutics; Karyopharm Therapeutics, Inc.; Kite Pharma, Inc.; Medac, GmbH; MedImmune; The Medical College of Wisconsin; *Mediware; *Merck & Co, Inc.; *Mesoblast; MesoScale Diagnostics, Inc.; Millennium, the Takeda Oncology Co.; *Miltenyi Biotec, Inc.; National Marrow Donor Program; *Neovii Biotech NA, Inc.; Novartis Pharmaceuticals Corporation; Otsuka Pharmaceutical Co, Ltd.—Japan; PCORI; *Pfizer, Inc; *Pharmacyclics, LLC; PIRCHE AG; *Sanofi Genzyme; *Seattle Genetics; Shire; Spectrum Pharmaceuticals, Inc.; St. Baldrick’s Foundation; *Sunesis Pharmaceuticals, Inc.; Swedish Orphan Biovitrum, Inc.; Takeda Oncology; Telomere Diagnostics, Inc.; and University of Minnesota. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration (HRSA) or any other agency of the U.S. Government. *Corporate Members

Author contributions

All listed authors participated in: (1) the conception and/or design of this study, data acquisition, and/or result interpretation; (2) drafting or revising the manuscript; and (3) approval of the final submitted manuscript. Dr. Turcotte has had full access to the data in the study and takes responsibility for the decision to submit for publication.

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Authors and Affiliations

  1. University of Minnesota Blood and Marrow Transplant Program, Minneapolis, MN, USA

    Lucie M. Turcotte

  2. Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA

    Tao Wang, Michael T. Hemmer & Mary M. Horowitz

  3. Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, WI, USA

    Tao Wang

  4. Center for International Blood and Marrow Transplant Research, National Marrow Donor Program/Be The Match, Minneapolis, MN, USA

    Stephen R. Spellman

  5. Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota Medical Center, Minneapolis, MN, USA

    Mukta Arora & Margaret A. MacMillan

  6. Utah Blood and Marrow Transplant Program, Salt Lake City, UT, USA

    Daniel Couriel

  7. Department of Stem Cell Transplantation, Division of Cancer Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    Amin Alousi

  8. Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    Joseph Pidala & Taiga Nishihori

  9. Division of Hematology, Oncology and Blood & Marrow Transplantation, Children’s Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, USA

    Hisham Abdel-Azim

  10. Department of Hematology Oncology and Bone Marrow Transplantation, The Children’s Mercy Hospitals and Clinics, Kansas City, MO, USA

    Ibrahim Ahmed

  11. University of Miami, Miami, FL, USA

    Amer Beitinjaneh

  12. Division of Pediatrics Hematology, Children’s Hospital of Orange County, Orange, CA, USA

    David Buchbinder

  13. Vanderbilt University Medical Center, Nashville, TN, USA

    Michael Byrne

  14. Division of Hematology/Oncology/Bone Marrow Transplantation, Department of Medicine, University of Wisconsin Hospital and Clinics, Madison, WI, USA

    Natalie Callander & Peiman Hematti

  15. Division of Cell Therapy and Hematologica, Department of Medicine, Duke University Medical Center, Durham, NC, USA

    Nelson Chao

  16. The University of Michigan, Ann Arbor, MI, USA

    Sung Wong Choi

  17. Blood and Marrow Transplant Program, Massachusetts General Hospital, Boston, MA, USA

    Zachariah DeFilipp

  18. Division of Cancer Epidemiology & Genetics, NIH-NCI Clinical Genetics Branch, Rockville, MD, USA

    Shahinaz M. Gadalla

  19. Hematology Research Centre, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, United Kingdom

    Robert Peter Gale

  20. Hematolgic Malignancies & Bone Marrow Transplant, Department of Medical Oncology, New York Presbyterian Hospital/Weill Cornell Medical Center, New York, NY, USA

    Usama Gergis

  21. Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA

    Shahrukh Hashmi

  22. Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

    Shahrukh Hashmi

  23. Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Leona Holmberg

  24. Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan

    Yoshihiro Inamoto

  25. Division of Hematology and Oncology, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA

    Rammurti T. Kamble

  26. Dana-Farber Cancer Institute/Boston Children’s Hospital, Boston, MA, USA

    Leslie Lehmann

  27. Wake Forest Baptist Health, Winston-Salem, NC, USA

    Zachariah McIver

  28. Division of Hematology/Oncology, University Florida College of Medicine, Gainesville, FL, USA

    Maxim Norkin

  29. Blood & Marrow Transplant Program, Kids Cancer Centre, Sydney Children’s Hospital, Sydney, Australia

    Tracey O’Brien

  30. Division of Therapeutic Immunology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden

    Richard F. Olsson

  31. Centre for Clinical Research Sormland, Uppsala University, Uppsala, Sweden

    Richard F. Olsson

  32. Blood and Marrow Transplantation Program and Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY, USA

    Ran Reshef

  33. Division of Hematology/Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

    Ayman Saad

  34. Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

    Bipin N. Savani

  35. Department of Hematology, Academische Ziekenhuis, Maastricht, Netherlands

    Harry C. Schouten

  36. Department of Hematology & Oncology, National Cancer Research Center East, Chiba, Japan

    Sachiko Seo

  37. The Blood and Marrow Transplant Group of Georgia, Northside Hospital, Atlanta, GA, USA

    Melhem Solh

  38. Department of Hematology/Oncology, Isala Clinic, Zwolle, The Netherlands

    Leo Verdonck

  39. Division of Hematology and Oncology, Washington University School of Medicine, St. Louis, MO, USA

    Ravi Vij

  40. Division of Bone Marrow Transplant, Seattle Cancer Care Alliance, Seattle, WA, USA

    Baldeep Wirk

  41. Blood & Marrow Transplantation Program, Division of Hematology/Oncology, Department of Medicine, Greenebaum Cancer Center, University of Maryland, Baltimore, MD, USA

    Jean Yared

  42. Department of Psychiatry, Medical College of Wisconsin, Milwaukee, WI, USA

    Jennifer M. Knight

  43. University of Colorado-Denver, Aurora, CO, USA

    Michael R. Verneris

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  1. Lucie M. Turcotte
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  2. Tao Wang
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Corresponding author

Correspondence to Lucie M. Turcotte.

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Turcotte, L., Wang, T., Hemmer, M.T. et al. Donor body mass index does not predict graft versus host disease following hematopoietic cell transplantation. Bone Marrow Transplant 53, 932–937 (2018). https://doi.org/10.1038/s41409-018-0100-1

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