Immune Recovery in Pediatric Transplantation: Can T Cell–Depleted Peripheral Blood Stem Cell Transplantation Beat Cord Blood Transplantation?

Abstract

The beginning of the 21st century has been a time of change in stem cell transplantation (SCT) practice, particularly in terms of donor selection for pediatric patients. We have witnessed a decline in peripheral blood SCT (PBSCT) in favor of bone marrow (BM) as a donor source, leading to less graft-versus-host disease (GVHD) [1]. With the acquisition of a critical pool of more than 12 million unrelated donors worldwide, this adult stem cell source has achieved some stability in terms of donor availability [2]. However, umbilical cord blood transplantation (CBT) has seen growing acceptance as a ready stem cell source with a low risk for GVHD even with donorerecipient mismatch. The perfection of CBT selection criteria alongwith concurrent improvements in the quality of cord blood products has produced continuing improvements in transplantation outcomes [3]. Successful new transplantation approaches with related haploidentical SCT promise to again reset the criteria for donor source selection [4]. The article by Oshrine et al [5] in this issue of The Journal opens up a further strategy, using partially T celledepleted (TCD) PBSCT as an alternative to CBT, especially in mismatched SCT. The study objectives of Oshrine et al’s Children’s Hospital of Philadelphia group derive from 2 competing problems facing mismatched allogeneic SCT: immune recovery and GVHD. Compared with CBT, PBSCT can transfer immunity to viruses (especially cytomegalovirus) from a seropositive donor, whereas CBT, with only virus-naive T cells, confers a greater risk of uncontrolled viral reactivation and disease [3]. However, compared with CBT, unmanipulated PBSCT carries an unacceptably high risk of GVHD [1]. These observations set the stage for exploring the option of TCD PBSCT. There is good reason to presume that TCD PBSCT can reduce the risk of GVHD to even below that of unmanipulated BM transplantation, but the ability of TCD PBSCT to establish immune function requires further investigation [6]. In fact, Oshrine et al’s study, which compared 55 TCD PBSCTs and 21 CBTs, showed distinct differences in the