title: Rapid memory T-cell reconstitution recapitulating CD45RA-depleted haploidentical transplant graft content in patients with hematologic malignancies.
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.
authors: 1] Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN, USA [2] Department of Pediatrics, University of Tennessee Health Science Center, College of Medicine, Memphis, TN, USA.
authors: B M
authors: BM
authors: Triplett
authors: 1] Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN, USA [2] Department of Pediatrics, University of Tennessee Health Science Center, College of Medicine, Memphis, TN, USA.
authors: D R
authors: DR
authors: Shook
authors: Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors: P
authors: 0000000334050893
authors: P
authors: Eldridge
authors: Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors: Y
authors: Y
authors: Li
authors: Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors: G
authors: G
authors: Kang
authors: 1] Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN, USA [2] Department of Pediatrics, University of Tennessee Health Science Center, College of Medicine, Memphis, TN, USA.
authors: M
authors: M
authors: Dallas
authors: 1] Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN, USA [2] Department of Pediatrics, University of Tennessee Health Science Center, College of Medicine, Memphis, TN, USA.
authors: C
authors: C
authors: Hartford
authors: 1] Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN, USA [2] Department of Pediatrics, University of Tennessee Health Science Center, College of Medicine, Memphis, TN, USA.
authors: A
authors: A
authors: Srinivasan
authors: Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors: W K
authors: WK
authors: Chan
authors: Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors: D
authors: D
authors: Suwannasaen
authors: 1] Department of Pediatrics, University of Tennessee Health Science Center, College of Medicine, Memphis, TN, USA [2] Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors: H
authors: H
authors: Inaba
authors: Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors: T E
authors: TE
authors: Merchant
authors: 1] Department of Pediatrics, University of Tennessee Health Science Center, College of Medicine, Memphis, TN, USA [2] Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors: C-H
authors: CH
authors: Pui
authors: 1] Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN, USA [2] Department of Pediatrics, University of Tennessee Health Science Center, College of Medicine, Memphis, TN, USA.
authors: W
authors: W
authors: Leung
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000401:mortality; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008297:Male; D011379:Prognosis; D013601:T-Lymphocytes; D055815:Young Adult
chemical_list: D017493:Leukocyte Common Antigens