PT-CY use in T cell-replete haploidentical HCT has significantly improved outcomes. However, hyperhydration with MESNA in CY administration poses a challenge, in patients with cardiac/ renal problems. PT-CY also increases VOD risk with prior exposure to hepatotoxic drugs. Katsanis et al. in a phase Ia trial in patients undergoing HCT for hematological malignancies showed that partially replacing PT-CY with PT-BEN had comparable outcomes to conventional PT-CY. We conducted an ambispective study in 54 patients [haplo (39), MSD(14), and MUD(1)] with nonmalignant hematological disorders and hematological malignancies in pediatric and adult patients undergoing HCT (MAC/RIC) from February 2019 to May 2024. GvHD prophylaxis comprised of PT-CY/BEN (PT-CY 50 mg/kg Day +3; PT-BEN 90 mg/m² Day +4) in a prospective arm (n = 21) and PT-CY/CY (50 mg/kg on Days +3, +4; comparator arm) in ambispective (prospective 12; retrospective 21) arm. In both groups, immunosuppression with CNI and MMF was also given. PT-CY/BEN was comparable to PT-CY/CY in terms of safety, efficacy, and GVHD prevention. In the PT-CY/BEN group, there was earlier neutrophil (0.008) and platelet (0.0057) engraftment with significantly lower BK viremia. Incidence of bacterial infection, TRM, EFS, and OS were comparable in both groups.