Abstract A050: ATG (anti-thymocyte globulin) with post-transplant cyclophosphamide (PTCy) significantly reduces GVHD and improves survival in haplo-HSCT (haploidentical hematopoietic stem cell transplantation): A systematic review and meta-analysis

Abstract BACKGROUND Graft-versus-host disease (GVHD) remains the most critical barrier to successful haploidentical hematopoietic stem cell transplantation (haplo-HSCT). A dual-agent prophylaxis combining anti-thymocyte globulin with post-transplant cyclophosphamide (ATG/PTCy) has emerged as a biologically synergistic and clinically disruptive strategy. This systematic review and meta-analysis evaluates whether ATG/PTCy provides significant advantages over conventional ATG- or PTCy-based regimens in hematologic malignancy recipients. METHOD Databases including PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were systematically searched. Eligible comparative studies reporting ATG/PTCy vs. ATG or PTCy alone were pooled. We included 14 studies (observational and RCTs), covering 1906 patients, most with acute leukemia, in either remission or non-remission at transplant. Meta-analyses were performed using RevMan 5.4.1. Dichotomous outcomes were calculated with Risk Ratio (RR); time-to-event outcomes were calculated with Hazard Ratio. Subgroup analysis explored dose modulation of ATG (2.5–5 vs 7.5–10 mg/kg) and PTCy (29–50 vs 80–100 mg/kg). Sensitivity testing excluded high-bias studies. Two-sided P < .05 was significant. RESULTS Acute GVHD: ATG/PTCy reduced grade II–IV GVHD compared with both ATG (RR 0.52; P < .00001) and PTCy (RR 0.53; P = .005). Severe GVHD (grade III–IV) was lower than with ATG (RR 0.33; P < .00001) but not significantly different from PTCy (RR 0.74; P = .23). These reductions persisted across varying ATG and PTCy dose ranges.Chronic GVHD: Risk was lower with ATG/PTCy than with ATG (RR 0.65; P = .0002), and particularly for extensive/moderate-severe disease (RR 0.50; P < .0001), but was not significantly different when compared with PTCy.Survival: Overall survival favored ATG/PTCy over both ATG (HR 0.75; P = .02) and PTCy (HR 0.70; P = .006). GVHD-free/relapse-free survival improved similarly (vs ATG HR 0.68; P = .0006; vs PTCy HR 0.70; P = .02), with the most effect seen where PTCy dosing was lower (29–50 mg/kg). Viral Reactivation & Infection-Related Mortality: CMV and EBV reactivation rates were comparable to ATG alone (CMV RR 1.04; P = .84; EBV RR 0.69; P = .22). However, ATG/PTCy showed higher reactivation than PTCy alone (CMV RR 1.42; P = .03; EBV RR 3.17; P = .0008). Despite increased viral reactivation, infection-related mortality did not differ between groups (vs ATG RR 1.07; P = .74; vs PTCy RR 1.07; P = .72). CONCLUSION The combined ATG/PTCy stands out as a strong advancement in GVHD prophylaxis, offering reductions in acute and chronic GVHD with improvement in survival outcomes. Importantly, these benefits are achieved without increasing relapse or infection-related mortality, although a higher rate of CMV and EBV reactivation highlights the need for vigilant post-transplant viral monitoring. We need more prospective trials to refine dose intensity, define patient-specific risk profiles, and guide its integration as a future standard of care.(Artificial intelligence was used to refine the abstract text) Citation Format: Anubhuti Sharma, Arundhati Sharma, Simranpreet Singh Daid, Manas Gunani, Marcelle Meseeha, Joyson Poulose. ATG (anti-thymocyte globulin) with post-transplant cyclophosphamide (PTCy) significantly reduces GVHD and improves survival in haplo-HSCT (haploidentical hematopoietic stem cell transplantation): A systematic review and meta-analysis [abstract]. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr A050.