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Successful mismatched hematopoietic stem cell transplantation for pediatric hemoglobinopathy by using ATG and post-transplant cyclophosphamide

Bone Marrow Transplantation volume 56, pages 2203–2211 (2021)Cite this article

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Abstract

The use of HLA-mismatched (un)related donors is historically associated with a higher incidence of transplant-related complications and mortality. However, the use of such donors may overcome the limited availability of HLA-matched donors for patients with β-thalassemia major (TM) and sickle cell disease (SCD). We investigated hematopoietic stem cell transplantation (HSCT) outcomes of pediatric TM and SCD patients treated with a mismatched donor using a treosulfan-based conditioning in combination with ATG and post-transplant cyclophosphamide (PT-CY) and compared these results to the clinical outcome of patients treated by matched donor HSCT without PT-CY. Thirty-eight children (n = 24 HLA-identical or 10/10-matched donors; n = 14 HLA-mismatched donors), who received a non-depleted bone marrow graft were included. Event-free survival (EFS) and GvHD were not higher in the mismatched PT-Cy group as compared to the matched group. Moreover, despite delayed neutrophil engraftment (day +22 vs. +26, p = 0.002) and immune recovery in the mismatched PT-Cy group, this did not result in more infectious complications. Therefore, we conclude that in the absence of an HLA-identical or a matched unrelated donor, HSCT with a mismatched unrelated or haploidentical donor in combination with ATG plus PT-CY can be considered a safe and effective treatment option for pediatric hemoglobinopathy patients.

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Fig. 1: Comparison of overall survival and event-free survival between the mismatched PT-CY and matched donor groups.
Fig. 2: Engraftment, infections, and incidence of GvHD in the mismatched PT-CY and matched donor group.
Fig. 3: Serum concentration of active ATG in patients treated with PT-CY and without PT-CY.
Fig. 4: Immune cell recovery post-HSCT in patients treated with PT-CY or without PT-CY.

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Acknowledgements

The authors would like to thank the nurses of the Stem Cell Transplant Units for their care of patients and assistance in obtaining patient samples. We acknowledge Gina van der Graaf for her help with measuring total and active ATG.

Funding

The work described in this project is funded in part by Neovii Biotech (Rapperswil, Switzerland). Neovii Biotech has not been involved in data generation, analysis, interpretation nor in the manuscript writing process.

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  1. Laboratory of Pediatric Immunology, Willem-Alexander Children’s Hospital, Leiden University Medical Center, Leiden, the Netherlands

    Lisa V. E. Oostenbrink, Emma S. Pool, Cornelia M. Jol-van der Zijde, Anja M. Jansen-Hoogendijk, Carly Vervat, Astrid G. S. van Halteren, Robbert G. M. Bredius, Frans J. W. Smiers, Maarten J. D. van Tol, Marco W. Schilham, Arjan C. Lankester & Alexander B. Mohseny

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Correspondence to Lisa V. E. Oostenbrink.

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Oostenbrink, L.V.E., Pool, E.S., Jol-van der Zijde, C.M. et al. Successful mismatched hematopoietic stem cell transplantation for pediatric hemoglobinopathy by using ATG and post-transplant cyclophosphamide. Bone Marrow Transplant 56, 2203–2211 (2021). https://doi.org/10.1038/s41409-021-01302-0

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