GvHD after umbilical cord blood transplantation for acute leukemia: an analysis of risk factors and effect on outcomes

• Type of Material: Article
• Authors: Yi-Bin Chen, Massachusetts General Hospital; Tao Wang, Medical College of Wisconsin; Michael T. Hemmer, Medical College of Wisconsin; Colleen Brady, Center for International Blood and Marrow Transplant Research; Daniel R. Couriel, Utah Blood and Marrow Transplant Program; Amin Alousi, University of Texas; Joseph Pidala, H Lee Moffitt Canc Ctr & Res Inst; Alvaro Urbano-Ispizua, University of Barcelona; Sung Won Choi, University of Michigan; Taiga Nishihori, H. Lee Moffitt Cancer Center and Research Institute; Takanori Teshima, Kyushu University Hospital; Yoshishiro Inamoto, National Cancer Center Hospital; Baldeep Wirk, Seattle Cancer Care Alliance; David I Marks, University Hospitals Bristol NHS Trust; Hisham Abdel-Azim, University of Southern California; Leslie Lehmann, Boston Childrens Hospital; Lolie Yu, Louisiana State University; Menachem Bitan, Tel Aviv Sourasky Medical Center; Mitchell S. Cairo, New York Medical College; Muna Qayed, Emory University; Rachel Salit, Fred Hutchinson Cancer Research Center
• Language: English
• Date: 2017-03-01
• Publisher: NATURE PUBLISHING GROUP
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 Macmillan Publishers Limited, part of Springer Nature.
• Final Published Version (URL): http://dx.doi.org/10.1038/bmt.2016.265
• Title of Journal or Parent Work: Bone Marrow Transplantation
• Volume: 52
• Issue: 3
• Start Page: 400
• End Page: 408
• Grant/Funding Information: The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement 5U24-CA076518 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 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-13-1-0039 and N00014-14-1-0028 from the Office of Naval Research; and grants from Alexion; *Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Be the Match Foundation; *Bristol Myers Squibb Oncology; *Celgene Corporation; *Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Gamida Cell Ltd.; Genentech, Inc.; Genzyme Corporation; *Gilead Sciences, Inc.; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; *Jazz Pharmaceuticals, Inc.; Jeff Gordon Children’s Foundation; The Leukemia & Lymphoma Society; The Medical College of Wisconsin; Merck & Co, Inc.; Mesoblast; *Millennium: The Takeda Oncology Co.; *Miltenyi Biotec, Inc.; National Marrow Donor Program; Neovii Biotech NA, Inc.; Novartis Pharmaceuticals Corporation; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Otsuka America Pharmaceutical, Inc.; Otsuka Pharmaceutical Co, Ltd. – Japan; Oxford Immunotec; Perkin Elmer, Inc.; Pharmacyclics; *Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; *Spectrum Pharmaceuticals, Inc.; St. Baldrick’s Foundation; *Sunesis Pharmaceuticals, Inc.; Swedish Orphan Biovitrum, Inc.; Telomere Diagnostics, Inc.; TerumoBCT; Therakos, Inc.; University of Minnesota; and *Wellpoint, Inc.
• Keywords: Oncology; STEM-CELLS; Science & Technology; Immunology; VERSUS-HOST-DISEASE; Hematology; CONDITIONING REGIMENS; MATCHED SIBLING DONORS; IMPACT; HEMATOLOGICAL MALIGNANCIES; WORKING GROUP; Biophysics; CHRONIC GRAFT; HEMATOPOIETIC-CELL TRANSPLANTATION; Transplantation; BONE-MARROW; Life Sciences & Biomedicine
• Research Categories: Health Sciences, General; Health Sciences, Immunology

Abstract

Using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, we analyzed 1404 umbilical cord blood transplantation (UCBT) patients (single (<18 years)=810, double (≥18 years)=594) with acute leukemia to define the incidence of acute GvHD (aGvHD) and chronic GvHD (cGvHD), analyze clinical risk factors and investigate outcomes. After single UCBT, 100-day incidence of grade II-IV aGvHD was 39% (95% confidence interval (CI), 36-43%), grade III-IV aGvHD was 18% (95% CI, 15-20%) and 1-year cGvHD was 27% (95% CI, 24-30%). After double UCBT, 100-day incidence of grade II-IV aGvHD was 45% (95% CI, 41-49%), grade III-IV aGvHD was 22% (95% CI, 19-26%) and 1-year cGvHD was 26% (95% CI, 22-29%). For single UCBT, multivariate analysis showed that absence of antithymocyte globulin (ATG) was associated with aGvHD, whereas prior aGvHD was associated with cGvHD. For double UCBT, absence of ATG and myeloablative conditioning were associated with aGvHD, whereas prior aGvHD predicted for cGvHD. Grade III-IV aGvHD led to worse survival, whereas cGvHD had no significant effect on disease-free or overall survival. GvHD is prevalent after UCBT with severe aGvHD leading to higher mortality. Future research in UCBT should prioritize prevention of GvHD.