A Randomized Pilot Trial comparing Anti-Thymocyte Globulin (ATG) with ATG plus Post Transplant Cyclophosphamide (PTCy) for Prophylaxis against Acute and Chronic Graft Versus Host Disease (GVHD) in Matched Donor Hematopoietic Cell Transplants (HCT)

In a randomized pilot trial we compared ATG (standard Arm A, 4.5 mg/kg) with ATG plus PTCy (experimental Arm BE, ATG 4.5 mg/kg, PTCy 100 mg/kg). The primary safety endpoint was overall survival at 100 days. We analyzed 79 patients with AML (n=55) or MDS (n=24). Median age (range) was 59 (19 to 74), 47 (59.5 %) were male. Conditioning was either myeloablative (n=49) or reduced intensity (n=30). Donors were 8/8 HLA-matched. Overall survival at 100 days was 95.0% (37 of 39 patients) vs 94.9% (38 of 40 patients) in arm A vs arm BE (p>0.9). In arms A versus BE, serious adverse events (SAEs) occurred in 26 (65.0%) and 25 (64.1%) patients, graft failure occurred in 3 and 1 patients (p>0.9), median (range) days to neutrophil engraftment were 19 (10-45) versus 22 (15-56) days p=0.007), cytomegalovirus and Epstein-Barr virus reactivations occurred in 11 and 7 patients (p=0.45) and in 6 and 5 patients (p=0.29). Overall survival at 12-months was 72.5% versus 75.8% (p-0.79), cumulative incidence at 6 months of relapse was 15.0% versus 15.7% (p=0.88) and of non-relapse mortality (NRM) 7.5% versus 8.0 (p=0.45). The combination of ATG and PTCy can safely be used in phase III trials.