Outcome of haploidentical peripheral blood allografts utilizing post-transplant cyclophosphamide compared to matched sibling and unrelated donor bone marrow allografts in pediatric patients with hematological malignancies: A single center analysis.

Abstract Background: Introduction of Post-Transplant Cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis has made haploidentical hematopoietic stem cell transplantation (HSCT) a common approach in adults, but pediatric experience is limited. Based on the encouraging adult data and to decrease the risk of graft failure, our center has increasingly used peripheral blood stem cells (PBSCs) from haploidentical donors (haplo) utilizing PTCy. Here we compare outcomes of traditional donor choices including matched sibling donor (MSD) and 10/10 HLA matched unrelated donor (MUD) receiving bone marrow graft with those receiving haplo PBSC in pediatric patients with hematological malignancies. Methods: This was a retrospective single-center study. Primary endpoint was the comparison of GVHD-free relapse-free survival (GRFS, defined as absence of acute GVHD grade III-IV, relapse, death or chronic GVHD requiring systemic therapy) for the three cohorts. Secondary endpoints included overall survival (OS), relapse-free survival (RFS), non-relapse mortality (NRM), incidence of acute (aGVHD) and chronic GVHD (cGVHD). Results: A total of 104 consecutive patients underwent first allo-HSCT for a hematological malignancy or myelodysplastic syndrome from January 2014 to December 2020 utilizing either a haploidentical family donor (PBSC, n=26), a matched sibling donor (bone marrow, n=31) or matched unrelated donor (bone marrow, n=47). Demographic and transplant characteristics were not significantly different among the cohorts, apart from remission status, with the haplo cohort having more patients in ≥CR3 prior to HSCT (p The cumulative incidence of aGVHD (grade II-IV or grade III-IV) was not significantly different among the cohorts. However, the cumulative incidence of cGVHD at 18 months was higher in the MUD bone marrow 31.7% versus 10.0% and 9.2% in the MSD and haplo cohorts respectively (p=0.02). There were no differences in the 18-month cumulative incidence of relapse or NRM. OS and RFS at 18 months for haplo were 80.7% (95CI 61.7%-100%) and 73.8% (95CI 55.5%-98.1%), for MUD 83.4% (95CI 72.8%-95.5%) and 70.3% (95CI 57.9%-85.3%) and for MSD 80.9% (95CI 66.9%-97.7%) and 66.5% (95CI 50.5%-87.5%), respectively without statistically significant differences among the cohorts. GRFS at 18 months for haplo cohort was 61% (95CI 43.3%-85.9%), for MUD 44.6% (95CI 31.8%-62.5%) and for MSD 62.1% (95CI 45.7-84.3%), p=0.26. Conclusions: Haploidentical PBSC transplants with PTCy had comparable outcomes to MSD and MUD bone marrow and less cGVHD compared to MUD bone marrow in children. The logistical advantages and lower resource burden of haploidentical transplants with PBSC make it a feasible alternative to MUD donors in children with hematological malignancies. Given that this is a retrospective comparison of transplantation platforms rather than donor types, further prospective studies are warranted.