Allogeneic Peripheral Blood Versus Bone Marrow Transplantation: Children Are Small Adults and More

Abstract

This issue of the Journal of Clinical Oncology reports the controversial findings of the International Bone Marrow Transplant Registry retrospective review comparing allogeneic stem-cell sources— bone marrow (BM) versus granulocyte colony-stimulating factor (G-CSF) –mobilized peripheral-blood stem cells (PBSC)—in children and adolescents. In their review of 143 PBSC and 630 BM human leukocyte antigen–identical sibling donor transplants in children with leukemia aged 8 to 20 years, Eapen et al found a higher rate of chronic graft-versus-host disease (GVHD) and treatment-related mortality (with similar relapse risk) in children receiving PBSC compared with BM. Overall, there was poorer survival when PBSC were used as the donor source, even after adjusting for relative risks. This is an unsettling finding, given that in 2003, close to 30% of pediatric matched sibling transplants reported to the International Bone Marrow Transplant Registry used PBSC as the donor source. The shift in clinical practice from using BM to G-CSF– mobilized PBSC as the hematopoietic progenitor cell source has arguably been among the most rapid and sweeping changes in clinical hematopoietic allogeneic transplantation this decade, second only to changes in the management of chronic myelogenous leukemia after the introduction of imatinib. Since it is common practice in pediatrics to extrapolate from adult therapy, the transition has occurred in both pediatrics and adult transplantation. In general, this is a reasonable approach, especially if there are no clear developmental or physiologic reasons to expect differences in efficacy or toxicity between children and adults. The biologic differences between the two stem-cell products include differences in both intermediate hematopoietic progenitors and T cells. In multiple animal and human trials, there has consistently been a strong correlation between the number of T cells in the transplanted graft and development of GVHD. The 10-fold increase in T cells in a PBSC graft initially made allogeneic transplant physicians hesitant to use PBSC as a stem-cell product, but experience has shown that PBSC can be safely used as an allogeneic stem-cell source. In the process of mobilization, the T cells have been exposed to G-CSF, which is known to modify T-cell responses in the direction of the T-helper-2 response, potentially explaining the tolerable GVHD observed. Early, predominately adult, experience with PBSC, frequently in patients with advanced malignancies, demonstrated more rapid count recovery and less early transplantrelated mortality (TRM), which translated into improved survival. As reviewed in the article by Eapen et al, subsequent results of randomized trials have been mixed. The overall conclusion is that PBSC transplantation outcomes are at least equivalent to, if not better than, BM as an allogeneic stem-cell source. Hence, there has been a rapid transition in clinical practice to the use of G-CSF–mobilized PBSC as the allogeneic donor source, with the rationale that more rapid postcollection recovery of the donor and more rapid post-transplantation recovery of hematopoiesis (with resultant shortening of hospital stay and decreased early transplant-related mortality in patients, especially those with advanced disease or poor performance status at the time of transplantation) were all important outcome goals, even if survivals was equivalent. The transition of clinical practice to use of G-CSF– mobilized PBSC has been slower in pediatrics, partially due to concerns of donor safety since donors are often minors. With increased experience in young child apheresis, there has been a growing acceptance that even young children can safely receive G-CSF and undergo apheresis, as recently reviewed by the Pediatric Blood and Marrow Transplant Consortium. JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 22 NUMBER 24 DECEMBER 15 2004