AML-025: Post-Transplant Cyclophosphamide versus Methotrexate-Based Regimen as Graft Versus Host Disease Prophylaxis after Allogeneic Haematopoietic Stem Cell Transplantation in Patients with Acute Leukemia

Abstract

Calcineurin inhibitor (CNI) and methotrexate are used as standard GVHD prophylaxis in HSCT. Trials using high dose post-transplant cyclophosphamide (PT-Cy) with or without immunosuppressive agents (IS) have shown success. Further studies are needed. To compare clinical outcomes of allo-HSCT using PT-Cy versus MTX as GVHD prophylaxis, we enrolled 80 patients (Pts) with acute leukaemia (53 males, 27 females) aged 18 to 60, who underwent matched and haplo allo-HSCT using reduced intensity chemotherapy at Maadi Armed Forces Hospital from 2014 to 2018. Median follow-up was 50 months after informed consent. Pts were randomized into 2 groups. The 1st group (40 patients) received MTX in the following doses: day +2 (15 mg), day +4 (10 mg), day +6 (10 mg) with cyclosporine (5 mg/kg) from day −3 till day +90 and mycophenolate (MMF) (2 −3gm/day) from day +1 till day +30. The 2nd group received PT-Cy (45 mg/kg/day) on days +3 and +4 with cyclosporine (5mg/kg) from day +5 till day +30 and MMF: (2-3 g/day) from day +5 till +30. At median 1-year post-allo, PT-Cy was associated with less incidence of chronic GVHD compared to MTX group (20%, 55%) respectively (P=0.002). Incidence of acute GVHD at day +100 was (40%, 32.5%) in group 1, 2 respectively (P=0.48). MTX group had higher incidence of renal & liver toxicity when compared to PT-Cy group (P=0.018, P=0.013) respectively. PT-Cy group had higher incidence of hemorrhagic cystitis when compared to MTX (P=0.006). In MTX group, renal toxicity caused mortality of 1 patient, hepatotoxicity caused mortality of 3 patients and HC caused mortality of 1 patient. In PT-Cy group, renal & hepatic toxicity caused no mortality while HC caused mortality of 3 patients. 87.5% of patients in group 1 and 90 % of patients in group 2 had full donor chimerism on day +30 (P=0.72). The cumulative incidence of relapse at 2 years post-allo was 17.5% for group 1 and 30% for group 2 (P >0.05). Cumulative 4 years disease free survival & overall survival (OS) in PT-Cy group was 45.7%, and 46.9%, respectively and for the MTX group, 43.4%, and 43.7%, respectively (P > 0.05). PT-Cy with addition of IS drugs has statistically significant difference in reducing the incidence of cGVHD compared with MTX based regimen without affecting engraftment, relapse, PFS & OS.