Gamma delta T cell reconstitution is associated with fewer infections and improved event-free survival after hematopoietic stem cell transplantation for pediatric leukemia

Biol Blood Marrow Transplant. 2015 Jan;21(1):130-6. doi: 10.1016/j.bbmt.2014.09.027. Epub 2014 Oct 16.

Abstract

After hematopoietic stem cell transplantation (HSCT), successful engraftment and immune recovery is necessary to protect the patient from relapse and infection. Many studies highlight the importance of conventional αβ T cell recovery after HSCT, but the impact of γδ T cell recovery has not been well described. Here, we investigate the recovery of γδ T cells in 102 pediatric patients with acute leukemia in first clinical remission who underwent allogeneic HSCT at St. Jude Children's Research Hospital from 1996 to 2011. Mean patient age was 10.5 ± 5.9 years (range, .6 to 25.2), and mean survivor follow-up was 2.7 ± 1.8 years (range, .12 to 6.0). Diagnoses included 59% patients with acute lymphoblastic leukemia and 41% patients with acute myelogenous leukemia. Multivariate analysis demonstrated significant impact of the maximum number of CD3(+), CD4(+), and CD8(+) T cells and donor source on the γδ T cell recovery (P < .0001, P < .0001, P < .0001, and P < .004, respectively). Univariate and multivariate models found the number of γδ T cells after HSCT to be associated with infections (P = .026 and P = .02, respectively). We found the probability of infections for patients with an elevated number of γδ T cells was significantly lower compared with patients with low or normal γδ T cells after HSCT (18% versus 54%; P = .025). Bacterial infections were not observed in patients with elevated γδ T cells. Finally, event-free survival was significantly higher in patients with enhanced γδ T cell reconstitution compared with patients with low/normal γδ T cell reconstitution after HSCT (91% versus 55%; P = .04). Thus, γδ T cells may play an important role in immune reconstitution after HSCT.

Keywords: Immune reconstitution; Infections; Leukemia; Pediatrics; γδ T cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Agents / therapeutic use
  • Child
  • Child, Preschool
  • Female
  • Graft Survival*
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / mortality
  • Graft vs Host Disease / pathology
  • Graft vs Host Disease / prevention & control
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Infant
  • Leukemia, Myeloid, Acute / immunology
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / pathology
  • Leukemia, Myeloid, Acute / therapy*
  • Male
  • Opportunistic Infections / immunology
  • Opportunistic Infections / mortality
  • Opportunistic Infections / pathology
  • Opportunistic Infections / prevention & control*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Prospective Studies
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • Survival Analysis
  • T-Lymphocytes / immunology*
  • Transplantation Conditioning*
  • Transplantation, Homologous
  • Treatment Outcome
  • Unrelated Donors

Substances

  • Antineoplastic Agents
  • Immunosuppressive Agents
  • Receptors, Antigen, T-Cell, gamma-delta