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  • Original Article
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Immune Recovery

Rapid memory T-cell reconstitution recapitulating CD45RA-depleted haploidentical transplant graft content in patients with hematologic malignancies

A Corrigendum to this article was published on 01 July 2015

This article has been updated

Abstract

T-cell depletion of an HLA-haploidentical graft is often used to prevent GVHD, but the procedure may lead to increased graft failure, relapse and infections due to delayed immune recovery. We hypothesized that selective depletion of the CD45RA+ subset can effectively reduce GVHD through removal of naive T cells, while providing improved donor immune reconstitution through adoptive transfer of CD45RA– memory T cells. Herein, we present results from the first 17 patients with poor-prognosis hematologic malignancy, who received haploidentical donor transplantation with CD45RA-depleted progenitor cell grafts following a novel reduced intensity conditioning regimen without TBI or serotherapy. Extensive depletion of CD45RA+ T cells and B cells, with preservation of abundant memory T cells, was consistently achieved in all 17 products. Neutrophil engraftment (median day +10) and full donor chimerism (median day +11) was rapidly achieved post transplantation. Early T-cell reconstitution directly correlated with the CD45RA-depleted graft content. T-cell function recovered rapidly with broad TCR Vβ spectra. There was no infection-related mortality in this heavily pretreated population, and no patient developed acute GVHD despite infusion of a median of >100 million per kilogram haploidentical T cells.

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  • 01 July 2015

    This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication

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Acknowledgements

We would like to thank our colleagues for data collection and clinical management. We also thank the many patients and families who participated in the transplantation and cellular therapy research program. This work is supported in part by the National Institutes of Health Cancer Center Support (CORE) grant P30 CA021765, the Assisi Foundation of Memphis, the Press On Fund, and the American Lebanese Syrian Associated Charities (ALSAC).

Author contributions

BMT and WL designed the research, analyzed and interpreted data, and wrote the manuscript; BMT, DRS, PE, MD, CH, AS, HI, TEM, CHP and WL provided study material and patient information and contributed to the interpretation of the data; GK provided statistical analysis; PE, YL, WKC and DS collected and performed laboratory analysis; all authors contributed to the revisions of the draft and approval of the final manuscript.

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Correspondence to B M Triplett.

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Supplementary Information accompanies this paper on Bone Marrow Transplantation website

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Triplett, B., Shook, D., Eldridge, P. et al. Rapid memory T-cell reconstitution recapitulating CD45RA-depleted haploidentical transplant graft content in patients with hematologic malignancies. Bone Marrow Transplant 50, 968–977 (2015). https://doi.org/10.1038/bmt.2014.324

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