T-cell depleted allogeneic hematopoietic stem cell transplant for the treatment of Fanconi anemia and MDS/AML - PubMed (original) (raw)

doi: 10.1038/s41409-023-02113-1. Epub 2023 Sep 29.

Elizabeth Klein 2, Audrey Mauguen 3, Binni Kunvarjee 4, Jaap Jan Boelens 2 5, Maria Cancio 2 5, Kevin J Curran 2 5, Nancy A Kernan 2 5, Susan E Prockop 2 5 6, Andromachi Scaradavou 2 5, Barbara Spitzer 2 5, Roni Tamari 7, Julianne Ruggiero 2, Joanne Torok-Castanza 2, Parinda A Mehta 8 9, Richard J O'Reilly 2 5, Farid Boulad 2 5

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T-cell depleted allogeneic hematopoietic stem cell transplant for the treatment of Fanconi anemia and MDS/AML

Alexandra M Satty et al. Bone Marrow Transplant. 2024 Jan.

Abstract

The only curative approach for myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) arising in patients with Fanconi anemia (FA) is allogeneic hematopoietic stem cell transplantation (HCT); however, HCT approaches are inconsistent and limited data on outcomes exist. We retrospectively evaluated outcomes of thirty patients with FA and MDS/AML who underwent first allogeneic HCT with a T-cell depleted (TCD) graft at our institution. Patients were transplanted on successive protocols with stepwise changes in cytoreduction and GVHD prophylaxis. All but two patients (93%) experienced durable hematopoietic engraftment. With median follow-up of 8.7 years, 5-year OS was 66.8% and DFS 53.8%. No significant differences in survival were found in patients with high-risk prognostic features (age ≥20 years, AML diagnosis, alternative donor graft) or when stratified by conditioning regimen. The 5-year cumulative incidences of relapse and NRM were 24.3% and 21.9%, respectively. NRM was higher in patients ≥20 years at HCT but did not otherwise differ. We herein demonstrate promising outcomes following allogeneic HCT for patients with FA and MDS/AML using TCD grafts, particularly in a cohort of high-risk patients with 50% ≥20 years and a majority receiving mismatched grafts. Future prospective studies are needed to compare this approach with other HCT platforms.

© 2023. The Author(s), under exclusive licence to Springer Nature Limited.

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References

    1. Tischkowitz MD, Hodgson SV. Fanconi anaemia. J Med Genet. 2003;40:1–10. https://doi.org/10.1136/jmg.40.1.1 . -DOI -PubMed -PMC
    1. Dror Y. Correcting the aberrant Fanconi anemia transcriptional program by gene therapy. Haematologica. 2023, https://doi.org/10.3324/haematol.2023.283031 .
    1. Berger R, Bernheim A, Gluckman E, Gisselbrecht C. In vitro effect of cyclophosphamide metabolites on chromosomes of Fanconi anaemia patients. Br J Haematol. 1980;45:565–8. https://doi.org/10.1111/j.1365-2141.1980.tb07179.x . -DOI -PubMed
    1. Auerbach AD, Adler B, O’Reilly RJ, Kirkpatrick D, Chaganti RS. Effect of procarbazine and cyclophosphamide on chromosome breakage in Fanconi anemia cells: relevance to bone marrow transplantation. Cancer Genet Cytogenet. 1983;9:25–36. https://doi.org/10.1016/0165-4608(83)90021-3 . -DOI -PubMed
    1. Gluckman E, Devergie A, Dutreix J. Radiosensitivity in Fanconi anaemia: application to the conditioning regimen for bone marrow transplantation. Br J Haematol. 1983;54:431–40. https://doi.org/10.1111/j.1365-2141.1983.tb02117.x . -DOI -PubMed

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