ATG exposure in T replete transplant for hematological malignancies: Real world analysis from BMT CTN 1202

Year: 2026

Type: article

Abstract: Traditional weight-based dosing results in variable rabbit anti-thymocyte globulin (rATG) clearance, delaying CD4 + Tcell-immune-reconstitution (CD4 + IR) and impacting outcomes. In a retrospective pharmacokinetic/pharmacodynamic analysis of patients undergoing first T-replete hematopoietic cell transplantation (HCT), enrolled on BMT CTN 1202, we estimated post-HCT rATG-exposures as area under the curve (arbitrary unit per day/milliliter [AUxd/mL]) using a validated pharmacokinetic-model. Results were compared to patients who did not receive rATG. Previously defined post-HCT rATG-exposure groups: A:<30, B:30-55 and C:≥55 AUxd/mL were correlated with outcomes of interest using cox-proportional-hazard and cause-specific-hazards models. 325 patients (median age 51 years) were included: 228 received rATG. Median post-HCT rATG-exposure was 44.1 (Range 6.2-125.0). Among patients who received rATG, higher exposure correlated with worse five-year overall survival (OS) (no-ATG:51%; group A:67%; B:49%; C:34%, p = 0.01), higher five-year relapse incidence (no-ATG:31%; A:27%; B: 42%; C: 58%, p < 0.001) and lower CD4 + IR (no-ATG:64%; A:73%; B:51%; C:19%, p = 0.001). Grade 2-4 acute graft versus host disease (GVHD) rates were: no-ATG:40%; A:26%, B:39%, C:35%, (p = 0.44). Any rATG-exposure was associated with lower moderate/severe chronic GVHD (HR:0.63, p = 0.025). Low post-HCT rATG-exposure (< 30AUxd/mL) but not absent correlated with higher OS, lower relapse, and lower GVHD related deaths. Model-based-dosing could be used to target optimal post-HCT rATG-exposure and improve HCT outcomes.

Source: Bone Marrow Transplantation

DOI: 10.1038/s41409-026-03032-7

Authors: Madhavi Lakkaraja, Audrey Mauguen, Kinga Hosszu, Devin McAvoy, Valerie Stewart, Gabrielle Schmidt, John E. Levine, Miguel-Angel Perales, Sergio A. Giralt, K. Scott Baker, Jaap Jan Boelens

Institutions: University of Washington, Fred Hutch Cancer Center, Memorial Sloan Kettering Cancer Center, National Marrow Donor Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, Weill Cornell Medicine

Language: English

Topic: Hematopoietic Stem Cell Transplantation

Subfield: Hematology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,990

Funders: U.S. Department of Health and Human Services, Sanofi, National Institutes of Health, Health Resources and Services Administration, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Allergy and Infectious Diseases

OpenAlex ID: W7214912918