Reduced dose PTCy in patients with acute myeloid leukemia receiving matched unrelated donor allogeneic hematopoietic stem cell transplantation.

6511 Background: Post-transplant cyclophosphamide (PTCy) at 50 mg/kg on D+3 & +4 after allogeneic hematopoietic cell transplantation (HCT) is established for graft-versus-host disease (GvHD) prophylaxis. PTCy causes significant toxicities, including bloodstream infections (BSI), delayed engraftment, viral reactivations, hemorrhagic cystitis (HC), cardiotoxicity, and fluid overload (FO), contributing to increased non-relapse mortality (NRM). Methods: In July 2024, we initiated a pilot to evaluate reduced (35 mg/kg on D+3 & +4) PTCy dosing (PTCy70). We included patients with AML receiving 10/10 matched unrelated donor peripheral blood grafts. All patients received fludarabine and busulfan conditioning. GvHD prophylaxis included anti-thymocyte globulin (ATG 2 mg/kg), a calcineurin inhibitor, & PTCy70. Outcomes were compared with a contemporary cohort receiving PTCy 100. Results: From July-Dec 2024, 30 patients received PTCy70. Baseline characteristics were comparable except for conditioning intensity (Table 1). Median follow up was 497 days (316 – 733) & 80 days (56 – 119) for PTCy100 & PTCy70, respectively. No graft failure occurred in PTCy70 group vs one in PTCy100 group. Median time to neutrophil engraftment was comparable, 20 days (19–21). Median time to platelet engraftment was shorter in the PTCy70 group (14 vs. 16 days, p=0.01). At D+30, the incidence of platelet engraftment was significantly higher in the PTCy70 group (87% vs. 81%, p=0.01).D+30 incidence of BSI was much lower in the PTCy70 group (30% vs. 59%, p=0.005). Most BSIs in both groups were caused by gram-positive organisms (71% vs. 77%, p=0.7). CMV at D+100 was 7.2% (95% CI: 1.2 – 21) in PTCy70 and 18.7% (95% CI: 12 – 27) in the PTCy100 group (p=0.14). None of the patients receiving PTCy70 developed HC vs. 11 in the PTCy100 group. FO occurred in 16 (53%) patients (grade 1: 12; grade 2: 4) receiving PTCy70, with none developing >grade 2 FO. There was no difference in the median duration of admission (31 days, p=0.9).Six patients receiving PTCy70 developed grade II-IV aGvHD. Four had grade II skin GvHD & responded to topical steroids. At D+100, there was no significant difference in grade II-IV (18.7% vs. 29%, p=0.29), grade III-IV acute GvHD (4.8% vs. 3.3%, p=0.80), and NRM (5.3% vs 1.8%, p=0.62). Conclusions: PTCy70 is associated with faster platelet engraftment & lower BSI, with no increase in aGVHD. PTCy70 also seems to reduce HC and viral reactivation. Extended follow-up is necessary to examine longer term outcomes. Baseline characteristics. PTCy 100 PTCy 70 p Age, years, median (IQR)Recipient 59 (49 – 66) 63.5 (57 – 67) 0.07 Myeloablative conditioning, n (%) 46 (41) 5 (17) 0.01 CMV serostatus, n (%)D+/R+D+/R-D-/R+D-/R- 57 (51)35 (31)4 (4)16 (14) 14 (47)6 (20)4 (13)6 (20) 0.13 CD34+ cell dose x 10 6 /kg, median (IQR) 7.5 (6.3 – 8.1) 6.7 (5.3 – 8) 0.07