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A phase II study of reduced intensity double umbilical cord blood transplantation using fludarabine, melphalan, and low dose total body irradiation

Bone Marrow Transplantation volume 55, pages 804–810 (2020)Cite this article

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Abstract

In this multicenter Phase 2 single arm study, we substituted low dose total body irradiation (TBI) for antithymocyte globulin (ATG) in a reduced intensity conditioning regimen with the intent to lower the risk for viral infections after double umbilical cord blood (UCB) transplantation. The conditioning regimen consisted of fludarabine (30 mg/m2/day, Day −7 to −2), melphalan (100 mg/m2/day, Day −1), and TBI (200cGy, Day 0). Graft-versus-host disease prophylaxis was sirolimus and tacrolimus. Thirty-one patients were treated on the protocol. The median time of follow-up for survivors was 24 months (range, 3.3–55.1). Nineteen patients experienced a total of 24 clinically significant viral reactivations or infections, with 1-year cumulative incidence rate of first significant viral event as 64% (95% CI, 43–79%), compared with our historical control of 53%. Within the context of these 24 clinically significant viral reactivations, there were a total of 10 infections with organ involvement. Nonrelapse mortality was 28% (95% CI 13–45%) at 2 years. The 2-year overall and progression-free survivals were 53% (95% CI 33–69%) and 47% (95% CI 28–64%), respectively. In conclusion, the substitution of low dose TBI for ATG did not decrease the incidence of significant viral events after UCB transplantation.

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Funding

Amgen Inc. provided clinical trial funding.

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Author notes

  1. These authors contributed equally: Karen K. Ballen, Corey S. Cutler

Authors and Affiliations

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

    Zachariah DeFilipp, Jami Brown, Steven McAfee, Bimalangshu R. Dey, Areej El-Jawahri, Thomas R. Spitzer & Yi-Bin Chen

  2. Department of Biostatistics and Computational Biology, Dana–Farber Cancer Institute, Boston, MA, USA

    Shuli Li

  3. Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA

    David Avigan, Vassiliki Boussiotis & Jacalyn Rosenblatt

  4. Division of Hematologic Malignancies, Dana–Farber Cancer Institute, Boston, MA, USA

    Philippe Armand, Vincent T. Ho, John Koreth, Sarah Nikiforow, Edwin P. Alyea, Jerome Ritz, Robert J. Soiffer, Joseph H. Antin & Corey S. Cutler

  5. Division of Hematology/Oncology, University of Virginia School of Medicine, Charlottesville, VA, USA

    Karen K. Ballen

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  1. Zachariah DeFilipp
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  20. Karen K. Ballen
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Correspondence to Corey S. Cutler.

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DeFilipp, Z., Li, S., Avigan, D. et al. A phase II study of reduced intensity double umbilical cord blood transplantation using fludarabine, melphalan, and low dose total body irradiation. Bone Marrow Transplant 55, 804–810 (2020). https://doi.org/10.1038/s41409-019-0715-x

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