TY - JOUR
T1 - Improved survival with model-based dosing of antithymocyte globulin in pediatric hematopoietic cell transplantation
AU - Admiraal, Rick
AU - Nierkens, Stefan
AU - Bierings, Marc B.
AU - Belderbos, Mirjam E.
AU - Huitema, Alwin D.
AU - Bredius, Robbert G.M.
AU - Jiang, Yilin
AU - Curran, Kevin J.
AU - Scaradavou, Andromachi
AU - Cancio, Maria I.
AU - Klein, Elizabeth
AU - Kollen, Wouter J.
AU - Bresters, Dorine
AU - Calkoen, Friso G.J.
AU - Versluijs, A. Birgitta
AU - Zwaan, C. Michel
AU - Boelens, Jaap Jan
AU - Lindemans, Caroline A.
N1 - Publisher Copyright:
© 2025 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.
PY - 2025/5/13
Y1 - 2025/5/13
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=105005797049&partnerID=8YFLogxK
U2 - 10.1182/bloodadvances.2024014836
DO - 10.1182/bloodadvances.2024014836
M3 - Article
C2 - 39983052
AN - SCOPUS:105005797049
SN - 2473-9529
VL - 9
SP - 2344
EP - 2353
JO - Blood Advances
JF - Blood Advances
IS - 9
ER -