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Incorporating posttransplant cyclophosphamide-based prophylaxis as standard-of-care outside the haploidentical setting: challenges and review of the literature

Bone Marrow Transplantation volume 55, pages 1041–1049 (2020)Cite this article

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Abstract

Posttransplant high-dose cyclophosphamide (PTCy) effectively prevents GvHD after haploidentical SCT. However, its use in HLA-matched SCT has been less explored. Fifty-six consecutive patients who underwent allo-SCT for hematological malignancies have been included in this prospective single-center protocol. Donors have been HLA-identical siblings, fully-matched unrelated or 1-allele-mismatched unrelated donors in 30%, 32%, and 37% of cases, respectively. Nine patients have received a TBI-containing MAC regimen, while the remaining (84%) received RIC platforms based on Fludarabine plus Busulfan/Melphalan. Due to the high graft failure (GF) rate (21%) in a preliminary analysis in the allo-RIC cohort (n = 29), protocol amendments have been implemented, with no further cases of GF after the introduction of mini-thiotepa (0/18). The overall incidence of grade II–IV acute GvHD is 24% (95% CI: 17–31%) with four steroid-refractory cases. Severe chronic GvHD has occurred in only 1 of 43 evaluable cases. The 1-year NRM and relapse are 18% (95% CI: 12–26%) and 30% (18–42%) and the OS and DFS are 78% and 64%, respectively. These outcomes support the feasibility of using PTCy as a SOC outside the haplo-setting, albeit mini-thiotepa (3 mg/kg) was incorporated in the standard allo-RIC platforms to prevent GF. Despite the limitations of a single-center experience and the short follow-up, these protocols show promising results with particular benefit in reducing the occurrence of moderate-to-severe GvHD.

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Author notes

  1. These author contributed equally: J. Sierra, R. Martino

Authors and Affiliations

  1. Hematology Department, Hospital de la Santa Creu i Sant Pau, Sant Pau and Jose Carreras Leukemia Research Institutes, Autonomous University of Barcelona, Barcelona, Spain

    I. García-Cadenas, R. Awol, A. Esquirol, S. Saavedra, A. Bosch-Vilaseca, S. Novelli, A. Garrido, J. López, M. Granell, C. Moreno, J. Briones, S. Brunet, J. Sierra & R. Martino

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García-Cadenas, I., Awol, R., Esquirol, A. et al. Incorporating posttransplant cyclophosphamide-based prophylaxis as standard-of-care outside the haploidentical setting: challenges and review of the literature. Bone Marrow Transplant 55, 1041–1049 (2020). https://doi.org/10.1038/s41409-019-0771-2

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