P145 | ENHANCED GVHD PROPHYLAXIS WITH LOW-DOSE GRAFALON^® AND POST-TRANSPLANT CYCLOPHOSPHAMIDE IN HAPLOIDENTICAL AND MISMATCHED UNRELATED DONOR STEM CELL TRANSPLANTATION

Originally designed for haploidentical bone marrow transplantation, PTCy has been extended to peripheral blood stem cell (PBSC) transplants. While ensuring robust engraftment and low relapse rates, this approach has been linked to a high incidence of acute GvHD (aGvHD) in this setting. Currently, no published data are available on the use of pretransplant Grafalon® in combination with PTCy. To address this gap and mitigate the risk of aGvHD, we investigated a novel prophylaxis strategy combining low-dose Grafalon® with PTCy. Since September 2022, we have implemented a combined GvHD prophylaxis protocol in adult patients undergoing haplo- or one-antigen MMUD transplants receiving a PBSC graft. The protocol includes low-dose ATG (Grafalon® at 10 mg/kg) on day -1, followed by cyclophosphamide at 50 mg/kg (or 35 mg/kg for patients >60 years or with cardiac comorbidities) on days +3 and +5 post-transplantation. We conducted a retrospective analysis of all consecutive patients treated with this approach between September 2022 and October 2024. Twelve patients were included: 10 with acute myeloid leukemia, 1 with non-Hodgkin lymphoma, and 1 with chronic myeloid leukemia. The median age was 62 years (range: 29–75). Six patients received haplo-HSCT, and six underwent MMUD HSCT. Mild-to-moderate infusion-related reactions occurred in 10/12 patients. Importantly, no cases of severe acute GvHD (aGvHD) were observed; grade 2 aGvHD developed in 6/12 patients. Chronic GvHD was limited to grade 2 in one patient and grade 1 in another, with no cases of moderate-to-severe chronic GvHD. Long-term infectious complications were limited, including two CMV reactivations (one requiring treatment) and one self-limiting EBV reactivation. Immune reconstitution assessment at >6 months post-transplant showed CD4+ counts >200/mmc in all patients. Non-relapse mortality occurred in one patient, while disease relapse was observed in three. At a median follow-up of 12 months (range: 2–18), 8/12 patients were alive and disease-free. The combination of low-dose Grafalon® and PTCy appears to be a safe and effective GvHD prophylaxis strategy, demonstrating excellent tolerability with no severe acute or chronic GvHD and without increasing the risks of infection or relapse. Larger prospective studies and longer follow-up are needed to confirm these findings and establish the long-term efficacy of this approach.