Improved survival with model-based dosing of antithymocyte globulin in pediatric hematopoietic cell transplantation Journal Article
| Authors: | Admiraal, R.; Nierkens, S.; Bierings, M. B.; Belderbos, M. E.; Huitema, A. D.; Bredius, R. G. M.; Jiang, Y.; Curran, K. J.; Scaradavou, A.; Cancio, M. I.; Klein, E.; Kollen, W. J.; Bresters, D.; Calkoen, F. G. J.; Versluijs, A. B.; Zwaan, C. M.; Boelens, J. J.; Lindemans, C. A. |
| Article Title: | Improved survival with model-based dosing of antithymocyte globulin in pediatric hematopoietic cell transplantation |
| Abstract: | 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 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. |
| Journal Title: | Blood Advances |
| Volume: | 9 |
| Issue: | 9 |
| ISSN: | 2473-9529 |
| Publisher: | American Society of Hematology |
| Date Published: | 2025-05-13 |
| Start Page: | 2344 |
| End Page: | 2353 |
| Language: | English |
| DOI: | 10.1182/bloodadvances.2024014836 |
| PUBMED: | 39983052 |
| PROVIDER: | scopus |
| PMCID: | PMC12142804 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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50Klein -
59Cancio -
216Boelens
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