Immunologic recovery in children after alternative donor allogeneic transplantation for hematologic malignancies: comparison of recipients of partially T cell-depleted peripheral blood stem cells and umbilical cord blood.
Impaired immunologic recovery (IR) after hematopoietic stem cell transplantation (HSCT) is associated with increased risk for infections and relapse. Stem cell source and graft manipulation influence the kinetics of IR. Partial T cell depletion of peripheral blood stem cell (PBSC) grafts is a novel alternative method of graft manipulation for children. We compared IR in children undergoing HSCT for hematologic malignancies receiving either T cell-depleted (TCD)-PBSCs (n = 55) or umbilical cord blood (UCB) (n = 21) over a 7-year period at a single institution. PBSC grafts underwent ex vivo negative selection for CD3(+) cells using the CliniMACS system with partial T cell add-back. Recovery of CD4(+) T cells was significantly delayed in TCD-PBSC recipients compared with UCB recipients, owing to impaired CD4(+)/CD45RA(+) (naïve) T cell lymphopoiesis. Recovery of total CD3(+) cells and CD3(+)/CD8(+) cells was similar in the 2 groups. The TCD-PBSC recipients had a marked deficit in CD19(+) and, to a lesser extent, IgA/IgM, owing to the need for B cell depletion of these grafts to attenuate the risk of lymphoproliferative disease after TCD HSCT. There were no significant between-group differences in response to mitogen stimulation, time to independence from intravenous immunoglobulin supplementation, or incidence of viral reactivation. Transplantation outcomes of relapse, transplantation-related mortality, event-free survival, and overall survival were similar in the 2 groups. Efforts to enhance IR after partial TCD-PBSC transplantation, such as selective αβ T cell depletion, hold promise for further improvement of this transplantation approach.
Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. Electronic address: oshrineb@email.chop.edu.
Benjamin R
BR
Oshrine
Yimei
Y
Li
David T
DT
Teachey
Jennifer
J
Heimall
David M
DM
Barrett
Nancy
N
Bunin
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D018572:Disease-Free Survival; D005260:Female; D019337:Hematologic Neoplasms / Q000276:immunology / Q000601:surgery*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D008212:Lymphocyte Depletion / Q000379:methods; D008297:Male; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000276:immunology*; D019172:Transplantation Conditioning / Q000009:adverse effects; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
Hematopoietic stem cell transplantation; Immune reconstitution; Pediatric; T cell depletion