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Individualized dose of anti-thymocyte globulin based on weight and pre-transplantation lymphocyte counts in pediatric patients: a single center experience

Bone Marrow Transplantation volume 59, pages 473–478 (2024)Cite this article

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Abstract

Anti-thymocyte globulin (ATG) has become a standard in preventing GVHD in related and unrelated donor transplantation, but there is no consensus on the best administration schedule. The PARACHUTE trial reported excellent CD4 immune reconstitution (CD4 IR) using a dosing schedule based on the patient’s weight and pre-conditioning absolute lymphocyte count (ALC). In 2015 we introduced the PARACHUTE dosing schedule for pediatric patients at our center. One hundred one patients were transplanted for malignant and non-malignant diseases. In this non-concurrent cohort CD4 IR+, defined by a single CD4 count >50/µL on day 90, was seen in 81% of patients. The incidence of grade II-IV and III to IV aGvHD was 26.6% and 15.3% and 5% for cGvHD with no severe cases. We found no difference in aGvHD between donor type and stem cell sources. Five-year EFS and OS were 77.5% and 83.5%. Grade III-IV GFRS was 75.2%. CD4 IR+ patients had better EFS (93.1% vs. 77.7%, p = 0.04) and lower non-relapse mortality (2.7% vs. 22.2%, p = 0.002). The PARACHUTE ATG dosing schedule individualized by weight and ALC results in good early immune reconstitution, low incidence of cGvHD, and favorable survival for patients with different disease groups, donor types, and stem cell sources.

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Fig. 1: Nomogram showing the total prescribed ATG dose in mg for patients in the study.
Fig. 2: Correlation between pretransplant ALC, donor type and CD4 IR.
Fig. 3: Kaplan Mayer curve showing 5-year nonrelapse mortality.
Fig. 4
Fig. 5

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Data availability

The datasets generated during/or analyzed during the current study are not available due to data protection but are available from the corresponding author on reasonable request. Figures and tables are available on https://doi.org/10.6084/m9.figshare.22814654.

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Acknowledgements

We thankfully acknowledge Dr. Jan Jap Boelens for his guidance through this work and thoughtful review of the manuscript.

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Author notes

  1. These authors contributed equally: Francisco Barriga, Angelica Wietstruck.

Authors and Affiliations

  1. Section of Hematology, Oncology and Stem Cell Transplantation. Division of Pediatrics, Pontificia Universidad Católica de Chile, Santiago, Chile

    Francisco Barriga, Angelica Wietstruck, Paula Catalán, Cristian Sotomayor, Pamela Zúñiga & Noemi Aguirre

  2. Department of Pediatric Infectious Diseases, Division of Pediatrics, Pontificia Universidad Católica de Chile, Santiago, Chile

    Clara Schulze-Schiappacasse, Cecilia Vizcaya & Nicole Le Corre

  3. Department of Public Health, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile

    Luis Villarroel

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Contributions

FB and AW were responsible for the design and review of the protocol, extracting and analyzing data, and writing of the report. CSc was responsible for database management and analysis. PC, CSo, PZ, NA were responsible for gathering data and review of the manuscript. CV was responsible of reviewing the manuscript.

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Correspondence to Francisco Barriga.

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Barriga, F., Wietstruck, A., Schulze-Schiappacasse, C. et al. Individualized dose of anti-thymocyte globulin based on weight and pre-transplantation lymphocyte counts in pediatric patients: a single center experience. Bone Marrow Transplant 59, 473–478 (2024). https://doi.org/10.1038/s41409-024-02206-5

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