biostudies-literatureAdmiraal RNCI NIH HHS2344-2353https://www.ebi.ac.uk/biostudies/studies/S-EPMC12142804biostudies-literatureUnknown9(9)<h4>Abstract</h4>Antithymocyte globulin (ATG) is used in pediatric allogeneic hematopoietic cell transplantation (HCT) to prevent graft-versus-host disease (GVHD) and graft failure (GF). Poor T-cell recovery, associated with increased mortality, is the main toxicity of ATG. Model-based precision dosing of ATG (MBD-ATG) minimizes toxicity while maintaining efficacy. We report updated results of the single-arm phase 2 PARACHUTE trial investigating MBD-ATG, combined with real-world experience using identical MBD-ATG. Consecutive patients receiving a first T-cell-replete HCT for any indication were evaluated. Results were compared with historical patients receiving conventional fixed ATG dosing (FIX-ATG). Primary outcome was overall survival (OS). The MBD-ATG group consisted of 214 patients (58 trial patients; 156 real-world patients); 100 patients received FIX-ATG. MBD-ATG led to superior OS compared with FIX-ATG (hazard ratio [HR] for death, 0.56; 95% confidence interval [CI], 0.34-0.93; P = .026), and lower treatment-related mortality (TRM; HR, 0.51; 95% CI, 0.29-0.92; P = .025). Successful T-cell reconstitution (>0.05 × 109/L CD4+ T cells twice within 100 after HCT) was improved in MBD-ATG vs FIX-ATG (87% ± 2% vs 47% ± 5%; P < .0001). The improved T-cell reconstitution led to lower TRM (HR, 0.19; 95% CI, 0.09-0.36; P < .0001). Incidence of grade 2-4 acute GVHD was comparable, whereas chronic GVHD (HR, 0.35; 95% CI, 0.17-0.72; P = .004) and GF (HR, 0.36; 95% CI, 0.13-0.97; P = .044) were both less frequent in MBD-ATG compared with FIX-ATG. MBD-ATG results in improved OS and reduced TRM, while reducing chronic GVHD and GF. This easy-to-implement approach improves outcomes after pediatric HCT, confirmatory studies are needed. The PARACHUTE trial is registered with the Dutch Trial Register as #NL4836.Blood advancesImproved survival with model-based dosing of antithymocyte globulin in pediatric hematopoietic cell transplantation.PMC12142804P30 CA008748Huitema ADVersluijs ABBoelens JJZwaan CMLindemans CABredius RGMCurran KJBierings MBJiang YScaradavou ACancio MIKlein ENierkens SCalkoen FGJBresters DAdmiraal RKollen WJBelderbos MEfalseImproved survival with model-based dosing of antithymocyte globulin in pediatric hematopoietic cell transplantation.<h4>Abstract</h4>Antithymocyte globulin (ATG) is used in pediatric allogeneic hematopoietic cell transplantation (HCT) to prevent graft-versus-host disease (GVHD) and graft failure (GF). Poor T-cell recovery, associated with increased mortality, is the main toxicity of ATG. Model-based precision dosing of ATG (MBD-ATG) minimizes toxicity while maintaining efficacy. We report updated results of the single-arm phase 2 PARACHUTE trial investigating MBD-ATG, combined with real-world experience using identical MBD-ATG. Consecutive patients receiving a first T-cell-replete HCT for any indication were evaluated. Results were compared with historical patients receiving conventional fixed ATG dosing (FIX-ATG). Primary outcome was overall survival (OS). The MBD-ATG group consisted of 214 patients (58 trial patients; 156 real-world patients); 100 patients received FIX-ATG. MBD-ATG led to superior OS compared with FIX-ATG (hazard ratio [HR] for death, 0.56; 95% confidence interval [CI], 0.34-0.93; P = .026), and lower treatment-related mortality (TRM; HR, 0.51; 95% CI, 0.29-0.92; P = .025). Successful T-cell reconstitution (>0.05 × 109/L CD4+ T cells twice within 100 after HCT) was improved in MBD-ATG vs FIX-ATG (87% ± 2% vs 47% ± 5%; P < .0001). The improved T-cell reconstitution led to lower TRM (HR, 0.19; 95% CI, 0.09-0.36; P < .0001). Incidence of grade 2-4 acute GVHD was comparable, whereas chronic GVHD (HR, 0.35; 95% CI, 0.17-0.72; P = .004) and GF (HR, 0.36; 95% CI, 0.13-0.97; P = .044) were both less frequent in MBD-ATG compared with FIX-ATG. MBD-ATG results in improved OS and reduced TRM, while reducing chronic GVHD and GF. This easy-to-implement approach improves outcomes after pediatric HCT, confirmatory studies are needed. The PARACHUTE trial is registered with the Dutch Trial Register as #NL4836.2025-01-01T00:00:00Z2025 May2026-06-02T05:58:54.144Z2026-04-15T03:09:44.559ZS-EPMC121428043998305210.1182/bloodadvances.2024014836