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How adoptive transfer of components of the donor immune system boosts GvL and prevents GvHD in HLA-haploidentical hematopoietic transplantation for acute leukemia

Bone Marrow Transplantation volume 59, pages 301–305 (2024)Cite this article

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Abstract

Why a new Perspective in allogeneic hematopoietic transplantation? A summary. Nowadays, for high-risk acute leukemia patients without an HLA-matched donor (sibling or volunteer), hematopoietic transplants that use HLA-haploidentical grafts combined with enhanced post transplant immune suppression (i.e., high-dose cyclophosphamide) are widely used. They are associated with low TRM rates. However, they are also associated with significant chronic GvHD while they only partially abrogate leukemia relapse rates. One may speculate that post-transplant immune suppression, required for GvHD prophylaxis, weakens the anti-leukemic potential of the graft. Historically, haploidentical transplants became feasible for the first time through transplantation of T cell-depleted peripheral blood hematopoietic progenitor cells. Lack of post-transplant immune suppression allowed the emergence of donor-versus-recipient NK-cell alloreactions that eradicated AML. In an attempt to improve these results we recently combined an age-adapted, irradiation-based conditioning regimen with transplant of T-cell-depleted grafts and infusion of regulatory and conventional T cells, without any post transplant immune suppression. With the obvious limitations of a single center experience, this protocol resulted in extremely low relapse and chronic GvHD rates and, consequently, in a remarkable 75% chronic GvHD/relapse-free survival in over 50 AML patients up to the age of 65 many of whom at high risk of relapse.

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Acknowledgements

LR is PI of the project “Adoptive immunotherapies with regulatory and conventional T cells and/or Natural Killer cells: safe and effective strategies to minimize the risk of leukemia relapse after allogeneic hematopoietic stem cell transplantation”, RF-2016-02364383 funded by Italian Ministry of Health. AP is PI of the project “Insights into Treg biology and T cell-based cancer immunotherapies”, START-UP grant number 20456 funded by Associazione Italiana per la Ricerca sul Cancro.

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  1. Department of Medicine and Surgery, Division of Hematology and Clinical Immunology, University of Perugia, Perugia, Italy

    Andrea Velardi, Antonella Mancusi, Loredana Ruggeri & Antonio Pierini

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Velardi, A., Mancusi, A., Ruggeri, L. et al. How adoptive transfer of components of the donor immune system boosts GvL and prevents GvHD in HLA-haploidentical hematopoietic transplantation for acute leukemia. Bone Marrow Transplant 59, 301–305 (2024). https://doi.org/10.1038/s41409-024-02199-1

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