Association between thymic function and allogeneic hematopoietic stem cell transplantation outcome: results of a pediatric study

Biol Blood Marrow Transplant. 2015 Jun;21(6):1099-105. doi: 10.1016/j.bbmt.2015.02.010. Epub 2015 Feb 20.

Abstract

Robust T cell function recovery has been shown to be crucial in determining allogeneic hematopoietic stem cell transplantation (HSCT) outcome, and there is growing evidence that the thymus plays a central role in regulating this process. We performed a long-term analysis of the role of thymic activity recovery in a population of pediatric patients undergoing allogeneic HSCT by signal joint T cell receptor excision circle (sjTREC) quantification. In this study, characterized by a long-term follow-up (median, 72 months), we found patients with higher levels of sjTRECs before transplantation had a statistically significant reduced risk of death compared with patients with lower values (relative risk, .31; 95% confidence interval, .30 to .32; P = .02), showing this different outcome was mainly related to a reduction of relapse incidence (14% versus 43%, P = .02). Unlike previous reports, we observed no correlation between sjTREC levels and lymphocyte recovery. Moreover, we confirmed that only graft-versus-host disease influenced thymic activity after transplantation. In conclusion, our results suggest an association between pretransplantation thymic activity and the long-term outcome of pediatric patients undergoing HSCT, mainly through a reduction of relapse opportunities.

Keywords: Allogeneic hematopoietic stem cell transplantation; Pediatric; sjTREC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Chronic Disease
  • Female
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / mortality
  • Graft vs Host Disease / pathology*
  • Graft vs Host Disease / prevention & control
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / mortality
  • Hematologic Neoplasms / pathology
  • Hematologic Neoplasms / therapy*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Infant
  • Infant, Newborn
  • Male
  • Myeloablative Agonists / therapeutic use
  • Prognosis
  • Prospective Studies
  • Receptors, Antigen, T-Cell, alpha-beta / analysis
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • Recurrence
  • Siblings
  • Survival Analysis
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology
  • Thymus Gland / immunology
  • Thymus Gland / pathology*
  • Transplantation Conditioning*
  • Transplantation, Homologous
  • Unrelated Donors
  • Young Adult

Substances

  • Immunosuppressive Agents
  • Myeloablative Agonists
  • Receptors, Antigen, T-Cell, alpha-beta