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

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.

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Acknowledgements

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. 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 US Government. The symbol ‘*’ indicates Corporate Members.

Author contributions

YC, CSC, TW, SRS and MA drafted the research plan; YC, CSC, TW, SRS, MA, MTH, DRC, AA, JP, AU, SWC, TN, TT, YI, BW, DIM, HA, LL, LY, MB, MSC, MQ, RS, RPG, RM, SJ, AB, BS, HF, IDL, JS, MA, MAK, MA, OR, RR, RFO, SH, SS, TRS, MLM and AL critically revised research plan; TW and MTH performed statistics; YC, CSC, TW, SRS and MA analyzed and interpreted data; YC, CSC, TW, SRS and MA drafted the paper; YC, CSC, TW, SRS, MA, MTH, DRC, AA, JP, AU, SWC, TN, TT, YI, BW, DIM, HA, LL, LY, MB, MSC, MQ, RS, RPG, RM, SJ, AB, BS, HF, IDL, JS, MA, MAK, MA, OR, RR, RFO, SH, SS, TRS, MLM and AL critically revised the paper.

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Correspondence to Y-B Chen.

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Chen, YB., Wang, T., Hemmer, M. et al. GvHD after umbilical cord blood transplantation for acute leukemia: an analysis of risk factors and effect on outcomes. Bone Marrow Transplant 52, 400–408 (2017). https://doi.org/10.1038/bmt.2016.265

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