Similar Survival after Bone Marrow Versus Peripheral Blood Stem Cell Transplantation from Matched Unrelated Donors in Children with Hematologic Malignancies.
Authors: Meisel Roland , Laws Hans-Juergen , Balzer Stephan , Bernbeck Benedikt , Kramm Christof , Schoenberger Stephan , Sinha Kumar , Troeger Anja , Wernet Peter , Goebel Ulrich , Enczmann Juergen , Dilloo Dagmar 
Published: October 2019

Peripheral blood stem cells (PBSC) are increasingly used instead of bone marrow (BM) for allogeneic haematopoietic stem cell transplantation (alloHSCT) in children. Prior studies in adults have suggested a comparable outcome with both stem cell sources in matched unrelated donor (MUD) transplantation. However, relative benefits of PBSC versus BM transplantation may substantially differ in children and adults due to a greater propensity to GvHD in older patients and a higher proliferation rate of blasts in childhood leukemia. Here we present the first comparison of the outcome following PBSC vs. BM transplantation from HLA-matched unrelated donors in an entirely pediatric cohort. Between 1992 and 2004, a total of 61 pediatric patients (pts) with haematologic malignancies underwent PBSC (n=38) or BM (n=23) transplantation from ≥ 5/6 HLA antigen-matched unrelated donors following myeloablative conditioning at our institution. PBSC and BM groups were comparable with regard to GvHD prophylaxis, disease category, disease status at transplant and recipient age, while differences were detected in recipients sex (more male pts in PBSC group, p=0.06), conditioning regimen (more busulfan-based conditioning in PBSC group, p=0.01) and median year of transplant (PBSC transplantations were more recent, p=0.001). Engraftment was achieved significantly faster after PBSC compared to BM transplantation (p=0.001). Median time to neutrophil engraftment was 18 (range: 9–28) and 24 (14–43) days for the PBSC and BM cohort, respectively. The rate of acute GvHD grade III/IV (PBSC vs. BM: 28.9% vs. 19.0%, p=0.54) and chronic GvHD (63.0% vs. 56.3%, p=0.75) was comparable between both groups. While there was a statistically non-significant trend towards increased risk of clinically extensive chronic GvHD following PBSC transplantation (48.1% vs. 25.0%, p=0.2), this did not translate into any detectable difference in treatment-related mortality (PBSC vs. BM: 28.9% vs. 26.1 %) or death of disease (21.7% vs. 21.1%) (p=1.0). With a median follow up of 3.4 years (PBSC) and 10.0 years (BM) overall survival (PBSC vs. BM: 47.5 ± 8.6 % vs. 51.8 ± 10.5 %; p = 0.88) and event-free survival (43.3 ± 8.3 % vs. 51.8 ± 10.5 %; p = 0.60) is without detectable difference between both groups. This result was confirmed in a multivariate analysis including stem cell source, recipient age, recipient sex, conditioning regimen, disease status at transplant and year of transplant as covariates, showing that advanced disease status at transplant is the only significant, independent risk factor for overall mortality (RR 2.4, 95%-CI 1.1–5.2, p=0.02). In conclusion, our data provide evidence that in pediatric recipients of MUD transplantation the use of PBSC instead of BM leads to a faster neutrophil engraftment and a trend towards higher incidence of extensive chronic GvHD. As overall survival and event-free survival is comparable when using PBSC and BM, PBSC is a valid alternate stem cell source for pediatric alloHSCT from MUDs. Supported by the Elterninitiative Kinderkrebsklinik e.V., Duesseldorf