Clinical Outcomes and the Impact of Anti-Thymocyte Globulin (ATG) and Chronic Graft Versus Host Disease (cGVHD) Following Pediatric Allogeneic Stem Cell Transplantation: A Comparison between Peripheral Blood and Bone Marrow as a Source of Stem Cells.

INTRODUCTION: The use of peripheral blood as a source of stem cells for pediatric allogeneic stem cell transplantation remains controversial. We present a retrospective analysis evaluating the safety and efficacy of allogeneic peripheral blood stem cell transplantation (PBSCT) compared to allogeneic bone marrow transplantation (BMT) for the treatment of acute leukemia at our centre. The impact of ATG added to the treatment regimen was also evaluated in this analysis.

METHODS: A chart review was conducted on all pediatric patients who underwent an allogeneic stem cell transplant for acute leukemia between April 1991 and August 2003 at the Alberta Children’s Hospital. All patients who received stem cells from HLA matched or one-antigen mismatched donors were included in this analysis. Data were analyzed using SPSS.

RESULTS: 85 children (ages 9 months to 17 years) met study criteria. 24 patients underwent a PBSCT while 61 patients, a BMT for the treatment of either ALL (n=54) or AML/MDS (n=31). Median follow up time was 5.9 years. Six of 24 patients in the PBSCT group, and 30 of the 61 patients in the BMT group received ATG (p=.042). There was a trend towards increased overall survival (OS) at 5 years following PBSCT (p=.078). Disease free survival (DFS) at 5 years following PBSCT and BMT was similar (p=.297). Subgroup analysis found no difference in OS or DFS between PBSCT and BMT in patients receiving (p=.221, p=.820) or not receiving ATG as part of the conditioning regimen (p=.448, p=.820). Chronic GVHD was increased following PBSCT (45.8%) compared to BMT (19.7%) (p=.015). The rate of severe cGVHD, however, was not significantly different (25% vs. 11.5% for PBSCT and BMT, p=.119) between the two groups. No patients receiving ATG prior to PBSCT developed cGVHD (p=.009). Addition of ATG to the transplant regimen had no impact on the rate of cGVHD following BMT (p=.221). There was no increase in mortality due to cGVHD following PBSCT (p=.243) or BMT (p=.865). Although, there was a trend to improved DFS in patients who developed cGVHD following PBSCT, this was not statistically significant (p=.057). Despite a statistically significant increase in TRM found in all patients with cGVHD at one year post-transplantation (p=.048), there was no difference in TRM between the PBSCT (4.2%) and BMT (14.8%) groups (p=.173).

CONCLUSION: Allogeneic PBSCT is a safe and effective alternative to allogeneic BMT for the treatment of acute leukemia in the pediatric population. Although there is an increased rate of cGVHD following PBSCT this does not appear to influence OS, DFS or TRM in our analysis. Addition of ATG into the transplant regimen decreases the occurrence of cGVHD after PBSCT. Studies to further assess the role of ATG in PBSCT are warranted.