Transplantation of Peripheral Blood Stem Cells from Unrelated Donors Is Not Associated with Inferior Survival Compared to Bone Marrow Transplantation in Children with Hematologic Malignancies - A Registry Analysis from the German/Austrian Pediatric Registry for Stem Cell Transplantation (PRST).
Authors: Meisel Roland , Spohr Caroline , Klingebiel Thomas , Dilloo Dagmar 
Published: October 2019

Abstract
The optimum stem cell source for allogeneic hematopoietic stem cell transplantation (HSCT) remains highly controversial. A recent study in older children and adolescents receiving HSCT from HLA-identical sibling donors has revealed higher mortality after peripheral blood stem cell (PBSC) compared to bone marrow (BM) transplantation (Eapen et al, JCO, 2004). However, despite the increasing use of PBSC in pediatric HSCT from matched unrelated donors (MUD), comparative studies on the relative risks and benefits of both stem cell sources are lacking. We therefore analysed the outcome of unrelated PBSC (n=118) and BM (n=102) transplants reported to the German/Austrian Pediatric Registry for Stem Cell Transplantation (PRST) between 1998 and 2003. Patients with hematologic malignancies (ALL, AML, CML, or MDS), who had received unmanipulated HSCT from ≥ 5/6 HLA antigen-matched unrelated donors following myeloablative conditioning were included into the analysis. PBSC and BM groups were comparable with regard to sex, age, CMV serostatus, GvHD prophylaxis, disease status at transplant, prophylactic growth factor use and degree of HLA-matching, while differences were detected in disease category (more MDS patients in PBSC group, p=0.02), transplanted cell dose (higher CD34-cell graft content in PBSC group, p=0.001) and median year of transplant (PBSC transplantations were more recent, p=0.01). Engraftment was achieved significantly faster after PBSC compared to BM transplantation: 15 vs. 19 days for neutrophil engraftment (p=0.001) and 21 vs. 25 days for platelet engraftment (p<0.01). The rate of acute GvHD grade II–IV (PBSC vs. BM: 44% vs. 39%, p=0.48) and severe acute GvHD Grade III/IV (29% vs. 21%, p=0.17) did not significantly differ between both groups. Moreover, the incidence of chronic GvHD (PBSC vs BM: 35% vs 33%, p=0.9) and extensive chronic GvHD (18% vs 18%, p=0.85) was identical at 3 years post transplant. In the PBSC group there was a statistically non-significant trend towards a higher risk for treatment-related mortality (PBSC vs BM: 34% vs 25%, p=0.14) and a lower risk for death of disease (PBSC vs. BM: 14% vs. 23%, p=0.16). However, this did no translate into a survival difference. With a median follow up of 2.9 years (PBSC) and 3.1 years (BM) overall survival (PBSC vs. BM: 50±5% vs. 46±6%; p=0.63) and event-free survival (45±5% vs. 44±6%; p=0.59) is comparable between both groups. This clinically most relevant result was confirmed in a multivariate analysis showing that advanced disease status at transplant (RR 2.4, 95%-CI 1.5–3.8, p=0.001) is a significant, independent risk factor for treatment failure, while the stem cell source (PBSC vs BM) has no effect (RR 1.1, 95%-CI 0.7–1.6, p=0.8). In summary, our data provide first evidence from a large, registry based analysis, that in pediatric recipients of MUD transplantation the use of PBSC instead of BM is not associated with inferior survival. Therefore, PBSC is a valid alternate stem cell source for pediatric HSCT from MUDs.