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Improved survival rate in T-cell depleted haploidentical hematopoietic cell transplantation over the last 15 years at a single institution

Abstract

T-cell depletion of an HLA-haploidentical (haplo) graft is often used to reduce the risk of graft-versus-host disease (GVHD), but the lack of donor T cells in the infused product may lead to graft failure, slow T-cell reconstitution, infections, and relapse. More selective T-cell depletion targeting CD45RA can effectively deplete naive T cells but preserve large numbers of memory T cells leading to robust engraftment of diverse T-cell populations and reduction of viremia in the early posttransplant period. Herein, we report the outcome of 143 pediatric and young adult hematologic malignancy patients receiving a first allogeneic hematopoietic cell transplantation (HCT) on six consecutive ex vivo T-cell depleted haploHCT protocols over the past 15 years at a single institution—including the first 50 patients on an active CD45RA-depleted haploHCT study in which patients also received NK-cells and pharmacological GvHD prophylaxis post transplant. Our data demonstrated an increase in the 3-year overall survival and event-free survival in nonchemorefractory recipients receiving CD45RA-depleted grafts (78.9% and 77.7%, respectively) compared with historic T-cell depleted haploHCT cohorts (46.7% and 42.7%, respectively, p = 0.004, and 0.003). This improvement was primarily due to a reduction in transplant related mortality without significant increase in the rates of GVHD.

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Acknowledgements

The authors would like to thank our colleagues for data collection and clinical management. Our thanks also go out to the many patients and families who participated in the transplantation and cellular therapy research program. We would like to recognize additional Principle Investigators of the historic T-cell depleted haploidentical donor therapeutic transplant trials initiated at this institution: Rupert Handgretinger, Eli Benaim, and Greg Hale. This work is supported in part by the National Institutes of Health Cancer Center Support (CORE) grant P30 CA021765, and the American Lebanese Syrian Associated Charities (ALSAC).

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Contribution: BMT and WL designed the therapeutic trial. BMT and SG analyzed and interpreted data, BMT and EM wrote the paper; EM, RM, AQ, ASr, AT, ASh, ASul, GM, WL, SG, and BMT provided patient information and data for analysis, contributed to interpretation of the data; GK and ASun provided statistical analysis; and all authors contributed to the revisions of the draft and approval of the final paper.

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Correspondence to Brandon M. Triplett.

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WL is currently an employee of Miltenyi Biotech, all efforts contributing to this work except for final paper review occurred prior to this employment. BMT received travel support from Miltenyi Biotech to present previously published work at EBMT annual meeting 2018. The other authors have no financial relationships or other conflicts of interest to disclose relevant to this paper. No author received an honorarium, grant, or other form of payment to produce the paper.

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Mamcarz, E., Madden, R., Qudeimat, A. et al. Improved survival rate in T-cell depleted haploidentical hematopoietic cell transplantation over the last 15 years at a single institution. Bone Marrow Transplant 55, 929–938 (2020). https://doi.org/10.1038/s41409-019-0750-7

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