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Next generation HLA-haploidentical HSCT

Bone Marrow Transplantation volume 50, pages S63–S66 (2015)Cite this article

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Abstract

Relapse is still the major cause of failure of allogeneic stem cell transplantation in high-risk acute leukemia patients. Indeed, whoever the donor and whatever the transplantation strategy, post-transplant relapse rates are ~30%, which is hardly satisfactory. The present phase 2 study analyzed the impact of adoptive immunotherapy with naturally occurring FoxP3+ T-regulatory cells (2 × 106 per kg) and conventional T lymphocytes (1 × 106 per kg) on prevention of GvHD and leukemia relapse in 43 high-risk adults undergoing full-haplotype mismatched transplantation without any post-transplant immunosuppression. Ninety-five percent of patients achieved full-donor type engraftment. Only 6/41 patients (15%) developed ⩾grade II acute GvHD. Specific CD4+ and CD8+ for opportunistic pathogens emerged significantly earlier than after standard T-cell-depleted haplo-transplantation. The probability of disease-free survival was 0.56. At a median follow-up of 46 months (range 18–65 months), only 2/41 evaluable patients have relapsed. The cumulative incidence of relapse was significantly lower than in historical controls (0.05 vs 0.21; P=0.03). These results demonstrate that the immunosuppressive potential of Tregs can be used to suppress GvHD without loss of the benefits of GvL activity. Humanized murine models provided insights into the mechanisms underlying separation of GvL from GvHD.

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Authors and Affiliations

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

    M F Martelli, M D Ianni, L Ruggeri, F Falzetti, A Carotti & A Velardi

  2. Department of Life, Hematology Section, Health and Environmental Sciences, University of L’Aquila, L’Aquila, Italy

    M D Ianni

  3. Department of Immunology, Weizmann Institute of Science, Rehovot, Israel

    Y Reisner

Authors
  1. M F Martelli
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  2. M D Ianni
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  3. L Ruggeri
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  4. F Falzetti
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  5. A Carotti
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  6. Y Reisner
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  7. A Velardi
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Correspondence to M F Martelli or L Ruggeri.

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Competing interests

YR has received consulting fees, owns equity in and has received grant support from Cell Source Ltd. LR has recieved grant support from LLS and AIRC. The remaining authors declare no conflict of interest.

Additional information

This article was published as part of a supplement, supported by WIS-CSP Foundation, in collaboration with Gilead, Milteny Biotec, Gamida cell, Adienne Pharma and Biotech, Medac hematology, Kiadis Pharma, Almog Diagnostic.

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Martelli, M., Ianni, M., Ruggeri, L. et al. Next generation HLA-haploidentical HSCT. Bone Marrow Transplant 50 (Suppl 2), S63–S66 (2015). https://doi.org/10.1038/bmt.2015.98

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