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HLA-haploidentical hematopoietic stem cells transplantation with regulatory and conventional T-cell adoptive immunotherapy in pediatric patients with very high-risk acute leukemia

Bone Marrow Transplantation volume 58, pages 526–533 (2023)Cite this article

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Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) is still needed for many children with very high-risk acute leukemia. An HLA-haploidentical family donor is a suitable option for those without an HLA-matched donor. Here we present outcomes of a novel HLA-haploidentical HSCT (haplo-HSCT) strategy with adoptive immunotherapy with thymic-derived CD4+CD25+ FoxP3+ regulatory T cells (Tregs) and conventional T cells (Tcons) performed between January 2017 and July 2021 in 20 children with high-risk leukemia. Median age was 14.5 years (range, 4–21), 15 had acute lymphoblastic leukemia, 5 acute myeloid leukemia. The conditioning regimen included total body irradiation (TBI), thiotepa, fludarabine, cyclophosphamide. Grafts contained a megadose of CD34+ cells (mean 12.4 × 106/Kg), Tregs (2 × 106/Kg) and Tcons (0.5–1 × 106/Kg). All patients achieved primary, sustained full-donor engraftment. Only one patient relapsed (5%). The incidence of non-relapse mortality was 15% (3/20 patients). Five/20 patients developed ≥ grade 2 acute Graft versus Host Disease (aGvHD). It resolved in 4 who are alive and disease-free; 1 patient developed chronic GvHD (cGvHD). The probability of GRFS was 60 ± 0.5% (95% CI: 2.1–4.2) (Fig. 6), CRFS was 79 ± 0.9% (95% CI: 3.2–4.9) as 16/20 patients are alive and leukemia-free. The median follow-up was 2.1 years (range 0.5 months–5.1 years). This innovative approach was associated with very promising outcomes of HSCT strategy in pediatric patients.

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Fig. 1: Transplantation schema.
Fig. 2: Graft-versus-Host Disease.
Fig. 3: T-cell recovery after transplantation.
Fig. 4: Pathogen-specific T cell response.
Fig. 5: Non-relapse mortality (NRM) and relapse.
Fig. 6: CRFS.
Fig. 7: GRFS.

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Acknowledgements

The authors thank Geraldine Anne Boyd and Fabio De Paola for editorial assistance, the nonprofit charity associations Comitato per la Vita Daniele Chianelli and nurses and the multidisciplinary group of the hematopoietic stem cell transplantation program. The authors also thank the patients and their caregivers for participating in this study.

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Authors and Affiliations

  1. Pediatric Oncology-Hematology Unit, Santa Maria della Misericordia Hospital, Perugia, Italy

    M. S. Massei, I. Capolsini, E. Mastrodicasa, K. Perruccio, F. Arcioni, C. Cerri, G. Gurdo, S. Sciabolacci, M. Brogna & M. Caniglia

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

    S. Sciabolacci, F. Falzetti, T. Zei, R. Iacucci Ostini, M. Merluzzi, A. Velardi, A. Pierini, L. Ruggeri, M. F. Martelli & A. Carotti

  3. Radiation Oncology Section, Santa Maria della Misericordia Hospital, Perugia, Italy

    B. M. Panizza, S. Saldi & C. Aristei

  4. Immunohaematology, Transfusion Service and Apheresis, Santa Maria della Misericordia Hospital, Perugia, Italy

    R. Tognellini, M. Marchesi & O. Minelli

  5. Radiation Oncology Section, Department of Medicine and Surgery, University of Perugia and Santa Maria della Misericordia Hospital, Perugia, Italy

    C. Aristei

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  1. M. S. Massei
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Contributions

MSM provided clinical care, performed research, and wrote the manuscript; IC performed research and evaluated suitability of donors; EM, KP, FA, CC, GG, SS and MB provided clinical care; FF, TZ and RIO processed the graft; SiSa designed and performed; RT performed HLA typing; OM evaluated suitability of donors; BMP and SS performed radiation treatment; MM collected clinical data; MaMa and OM evaluated suitability of donors and performed leukaphereses and photophereses; CA supervised radiation therapy and reviewed the manuscript; AV, AP, LR, MFM and AC reviewed the manuscript; MC provided clinical care, supervised the pediatric transplantation program, and reviewed the manuscript.

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Correspondence to M. S. Massei.

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Massei, M.S., Capolsini, I., Mastrodicasa, E. et al. HLA-haploidentical hematopoietic stem cells transplantation with regulatory and conventional T-cell adoptive immunotherapy in pediatric patients with very high-risk acute leukemia. Bone Marrow Transplant 58, 526–533 (2023). https://doi.org/10.1038/s41409-023-01911-x

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