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Addition of ATG to non-myeloablative peripheral blood haploidentical transplant with PTCY decreases acute GVHD rates and improves GVHD-relapse free survival

Bone Marrow Transplantation volume 58, pages 723–726 (2023)Cite this article

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Allogeneic hematopoietic stem cell transplantation using a T-cell-replete HLA-haploidentical graft (h-HSCT) is now routinely performed in most centers, especially for patients lacking a suitable matched donor [1]. The so-called Baltimore non-myeloablative (NMA) regimen uses high-dose post-transplant cyclophosphamide (PTCY) and has been demonstrated to be safe and effective to prevent graft rejection and graft-versus-host disease (GVHD) [2]. However, the relapse rate remains relatively high after this regimen (up to 46/51%) [2, 3], suggesting that other regimen should be tested in order to prevent disease reoccurrence. We have recently reported that with a Baltimore-like regimen with clofarabine (Clo-Baltimore regimen, CloB), the relapse rate was reduced to 25% in the setting of myeloid malignancies [4]. This new regimen uses the Baltimore backbone, but replacing fludarabine by the second-generation purine nucleoside analogue clofarabine, peripheral blood stem cells (PBSC) as graft source instead of bone marrow (BM), and cyclosporine A (CSA)/mycophenolate mofetil (MMF) in replacement of tacrolimus/MMF [4].

In spite of the use of PTCY, which depletes most alloreactive T-cells in vivo, GVHD remains a major cause of morbidity and mortality in h-HSCT recipients [5]. The administration of anti-thymocyte globulin (ATG) is a standard of care in the matched setting. It allows for in vivo recipient and donor T-cell depletion, thus reducing the risk of GVHD, at the price of potentially reducing the graft-versus-leukemia (GVL) effect and increasing the risk of opportunistic infection [6]. Its concomitant use with PTCY as GVHD prophylaxis after a myeloablative conditioning (MAC) has however been reported as safe and effective within the h-HSCT setting [7]. As acute GVHD rate was as high as 56% using our CloB regimen, here we investigated whether the addition of ATG to NMA CloB with PTCY was beneficial in terms of GVHD rates and transplantation outcomes.

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Data availability

The data that support the findings of this study are available from the corresponding author on reasonable request. The principal investigators MJ and PC had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis

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Acknowledgements

We acknowledge the paramedical staff of the Hematology Department of Nantes University Hospital for their assistance with the study, none of whom was compensated for his or her contributions.

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Authors and Affiliations

  1. Hematology Department, Nantes University Hospital, Nantes, France

    Maxime Jullien, Amandine Le Bourgeois, Pierre Peterlin, Alice Garnier, Thierry Guillaume & Patrice Chevallier

  2. INSERM UMR1232, CRCINA IRS-UN, University of Nantes, Nantes, France

    Thierry Guillaume, Marie C. Béné & Patrice Chevallier

  3. Hematology Biology, Nantes University Hospital, Nantes, France

    Marie C. Béné

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  1. Maxime Jullien
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  2. Amandine Le Bourgeois
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  4. Alice Garnier
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Contributions

MJ and PC designed, performed, coordinated the research, analyzed, interpreted the data, and wrote the manuscript. MJ performed statistical analyses and generated the figures. ALB, PP, AG, TG and MCB included patients, contributed data and commented on the manuscript.

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Correspondence to Patrice Chevallier.

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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.

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Jullien, M., Le Bourgeois, A., Peterlin, P. et al. Addition of ATG to non-myeloablative peripheral blood haploidentical transplant with PTCY decreases acute GVHD rates and improves GVHD-relapse free survival. Bone Marrow Transplant 58, 723–726 (2023). https://doi.org/10.1038/s41409-023-01956-y

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