Comparison of Transplant Outcomes in Patients with Acute Lymphoblastic Leukemia after Haploidentical Transplant with Post-Transplant Cyclophosphamide or Matched Unrelated Donor Transplant.

Transplant outcomes for patients with acute lymphoblastic leukemia (ALL) after haploidentical hematopoietic cell transplantation (haploHCT) with post-transplant cyclophosphamide (PTCy) compared to an HLA matched unrelated donors (MUD) transplantation are unknown. We, therefore retrospectively compared outcomes of 487 patients with ALL who underwent haploHCT with PTCy, reported from the participating centers (TCT-RC and EBMT) from 01/2005 to 06/2018, with a matched cohort of 974 patients (1:2 ratio) who underwent MUD-HCT and were reported to the EBMT. Patients were matched for sex, disease stage (CR1, CR2, other), disease risk (high or others), Philadelphia chromosome status (positive or negative), and conditioning regimen (MAC or RIC). Other significant differences in patient/transplant characteristics were adjusted for. Median age at HCT was 33 years (range: 18-73) for haplo and 36 years (range: 18-76) for MUD; (p=0.024). Median time from diagnosis to transplant was significantly longer in haploHCT (at 6 months: 23% vs. 29%; p=0.024). More patients in the haplo group received a female-to-male transplantation (27% vs. 13%; p< 0.0001) and BM as graft source (48% Vs 17%; p< 0.0001) compared with MUD. Calcineurin/methotrexate-based regime was the most commonly used prophylaxis in MUD-HCT, with ATG being added in 64% of cases. With a median follow up of 2 and 3 years in haplo and MUD, respectively, there was no statistical differences in overall survival (OS), (p=0.82); GvHD- and relapse- free survival (GRFS), (p=0.78); relapse rate, (p=0.88); or non-relapse mortality (NRM), (p=0.86) between haplo- and MUD-HCT recipients after adjusting for all covariates. (Fig 1) GvHD rates and severity were not different in patients undergoing haplo compared to those undergoing MUD HCT, possibly due to the use of ATG in 2/3 of patients with MUD HCT. However, mortality related to GVHD was significantly lower in patients undergoing haploHCT (HR= 0.45, p=0.003). We next did subgroup analysis based on conditioning intensity, disease status in first remission, Philadelphia chromosome status, and stem cell source. OS, disease-free survival (DFS), relapse rate and NRM were comparable between patients undergoing haplo and MUD HCT. Engraftment was faster in MUD if RIC was used (HR=0.75, p=0.05), grade 2-4 acute GvHD was lower in haplo if BM was the graft source (HR =0.57, p=0.04). Severe chronic GvHD was lower in haplo if transplant was done in CR1 (HR 0.52, p=0.05) and if BM was the graft source (HR 0.45 p=0.07). In conclusion, in this large retrospective analysis, outcomes of patients with ALL undergoing transplant from a haplo donor with PTCy is comparable with those undergoing an 8/8 MUD transplantations in subgroups analysis and regardless of the disease and Philadelphia chromosome status. [ABSTRACT FROM AUTHOR]