Umbilical Cord Blood or HLA-Haploidentical Transplantation: Real-World Outcomes versus Randomized Trial Outcomes

Paul V. O'Donnell, Claudio G. Brunstein, Ephraim J. Fuchs, Mei Jie Zhang, Mariam Allbee-Johnson, Joseph H. Antin, Eric S. Leifer, Hany Elmariah, Michael R. Grunwald, Hamza Hashmi, Mary M. Horowitz, John M. Magenau, Navneet Majhail, Filippo Milano, Lawrence E. Morris, Andrew R. Rezvani, Joseph P. McGuirk, Richard J. Jones, Mary Eapen

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12 Scopus citations


Randomized clinical trials offer the highest-quality data for modifying clinical practice. Results of a phase III randomized trial of nonmyeloablative transplantation for adults with high-risk hematologic malignancies with 2 umbilical cord blood (UCB) units (n = 183) or HLA-haploidentical relative bone marrow (Haplo-BM; n = 154) revealed a 2-year progression-free survival (PFS) of 41% after Haplo-BM transplantation and 35% after 2-unit UCB transplantation (P = .41), with overall survival (OS) of 57% and 46%, respectively (P = .04). We sought to examine the generalizability of BMT CTN 1101 to a contemporaneous cohort beyond the trial's prespecified 2-year outcomes. All transplantations were performed between June 2012 and June 2018 in the United States. We hypothesized that the results of a rigorous phase III randomized trial would be generalizable. Changes in graft selection for HLA-haploidentical relative transplantation during the trial period allowed comparison of outcomes after transplantation with Haplo-BM with those after haploidentical peripheral blood (Haplo-PB). The trial's broad eligibility criteria were applied to the data source of the Center for International Blood and Marrow Transplant Research to select nontrial subjects. Extended follow-up of trial subjects was obtained from this data source. Three separate analyses were performed: (1) trial subjects beyond the trial's 2-year endpoint; (2) comparison of trial subjects with a contemporaneous cohort of nontrial subjects (195 2-unit UCB, 358 Haplo-BM, and 403 Haplo-PB); and (3) comparison of nontrial subjects by donor and graft type. Multivariate analyses were performed using Cox proportional hazards models for comparison of outcomes by treatment groups. With longer follow-up of the trial cohorts, 5-year PFS (37% versus 29%; P = .08) and OS (42% versus 36%; P = .06) were not significantly different between the treatment groups. We then compared the trial results with outcomes of comparable real-world transplantations. Five-year OS did not differ between trial and nontrial 2-unit UCB transplantations (36% versus 41%; P = .48) or between trial and nontrial Haplo-BM transplantations (42% versus 47%; P = .80), confirming generalizability. The randomized trial did not accrue as planned and therefore lacked the statistical power to detect a 15% difference in PFS. With substantially larger numbers of nontrial Haplo-BM transplantations, 5-year survival was higher after nontrial Haplo-BM compared with trial 2-unit UCB (47% versus 36%; P = .012). Nontrial patients who underwent Haplo-PB transplantation had higher 5-year survival (54%) compared with trial Haplo-BM (hazard ratio [HR], 0.76; P = .044) and nontrial Haplo-BM (HR, 0.78; P = .026). Similarly, survival was better after Haplo-PB compared with trial UCB (HR, 0.57; P < .0001) and nontrial UCB (HR, 0.63; P = .0002). When considering alternative donor low-intensity conditioning regimen transplantation, a haploidentical relative is preferred, and PB is the preferred graft source.

Original languageEnglish (US)
Pages (from-to)109.e1-109.e8
JournalTransplantation and Cellular Therapy
Issue number2
StatePublished - Feb 2022

Bibliographical note

Funding Information:
Financial disclosure: Support for this study was provided by Grants U10HL069294 and U24HL138660 to the Blood and Marrow Transplant Clinical Trials Network from the National Heart, Lung and Blood Institute and National Cancer Institute. The Center for International Blood and Marrow Transplant Research is supported by Grant U24-CA076518 from the National Cancer Institute, the National Heart, Lung and Blood Institute, and the National Institute of Allergy and Infectious Diseases and Contract HHSH234200637015C from the Health Resources and Services Administration, Department of Health and Human Services (HRSA/DHHS). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, HRSA/DHHS, or any other agency of the US government.

Publisher Copyright:
© 2021 The American Society for Transplantation and Cellular Therapy


  • Cord blood
  • HLA-haploidentical
  • Leukemia
  • Lymphoma
  • Nonmyeloablative regimen
  • Survival


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