Open AccessRapid memory T-cell reconstitution recapitulating CD45RA-depleted haploidentical transplant graft content in patients with hematologic malignancies
Author(s) -
Brandon M. Triplett,
Shook Dr,
Paul W. Eldridge,
Li Y,
Guolian Kang,
Mari Dallas,
Christine Hartford,
Ashok Srinivasan,
Chan Wk,
Duangchan Suwannasaen,
Hiroto Inaba,
Merchant Te,
Pui Ch,
Wing Leung
Publication year - 2015
Publication title -
bone marrow transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.609
H-Index - 127
eISSN - 1476-5365
pISSN - 0268-3369
DOI - 10.1038/bmt.2014.324
Subject(s) - medicine , hematologic neoplasms , hematopoietic cell , transplantation , stem cell , hematology , graft versus host disease , immunology , haematopoiesis , biology , genetics
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.