Bodyweight and Absolute Lymphocyte Count-Based Dosing of Rabbit Anti-thymocyte Globulin Results in Early CD4⁺ Immune Reconstitution in Patients with Inborn Errors of Metabolism Undergoing Umbilical Cord Blood Transplantation.

IF 3.6 3区医学 Q2 HEMATOLOGY Transplantation and Cellular Therapy Pub Date : 2025-02-04 DOI:10.1016/j.jtct.2025.01.893

Daniel Drozdov, Jessica Kandil, Susie E Long, Connor Demorest, Qing Cao, Troy C Lund, Ashish O Gupta, Jaap Jan Boelens, Paul J Orchard

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Abstract

Background: Rabbit anti-thymocyte globulin (rATG) decreases the risk of graft failure and graft-versus-host disease (GVHD) in a setting of allogenic hematopoietic cell transplantation (HCT) but has highly variable pharmacokinetics. Recently, it was shown that a dosing nomogram based on recipient bodyweight and absolute lymphocyte count reduced rATG overexposure, which led to faster immune reconstitution. The aim of this study is to evaluate the feasibility and benefits of using an rATG dosing nomogram to achieve early CD4⁺ immune reconstitution in pediatric patients with inborn errors of metabolism (IEM) undergoing umbilical cord blood transplantation.

Methods: The rATG dosing nomogram in pediatric patients with IEM receiving an umbilical cord blood transplant with busulfan-based myeloablative conditioning at the University of Minnesota Masonic Children's Hospital was used prospectively since 2017. The primary endpoint was CD4⁺ immune reconstitution (>50 CD4⁺ T-cells/mL) within 100 days after HCT. Secondary endpoints included overall survival, graft failure, acute and chronic GVHD, and viral reactivations.

Results: A total of 27 patients were included in the study. Median follow-up time was 31 months (interquartile range [IQR], 22-38) and median age was 1.5 years (IQR, 0.7-3.9). The underlying disease was Hurler syndrome in 17 (63%), Hunter syndrome in 4 (15%), and cerebral adrenoleukodystrophy in 4 (15%) patients; 2 patients were transplanted for other IEM. The CD4⁺ recovery (>50 CD4⁺ T cells/mL) at 100 days post-HCT was reached in 22 (85%) of 26 patients. Overall survival was 83% (95% confidence interval [CI], 67%-100%). No graft failure was observed. Two (7%) patients developed acute GVHD grade II to IV and no patients had chronic GVHD. Six patients (22%) had cytomegalovirus (CMV) viremia. One patient had Epstein-Barr virus reactivation requiring treatment.

Conclusion: In patients with IEM, individualized dosing of rATG was associated with a robust and early CD4⁺ immune reconstitution, with no graft failures and low GVHD incidence.

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