Thiotepa, Fludarabine, and Busulfan Conditioning Regimen before T Cell-Replete Haploidentical Transplantation with Post-Transplant Cyclophosphamide for Acute Myeloid Leukemia: A Bicentric Experience of 100 Patients

Thomas Pagliardini, Lucas Castagna, Samia Harbi, Matteo Della Porta, Jerome Rey, Sabine Fürst, Stefania Bramanti, Colombe Saillard, Faezeh Legrand, Valerio Maisano, Catherine Faucher, Angela Granata, Marie-Anne Hospital, Wang Lining, Pierre-Jean Weiller, Boris Calmels, Aude Charbonnier, Claude Lemarie, Christian Chabannon, Norbert VeyDjamel Mokart, Didier Blaise, Raynier Devillier

Research output: Contribution to journalArticle

Abstract

Haploidentical stem cell transplantation (haplo-SCT) with post-transplant cyclophosphamide (PT-Cy) is an alternative treatment for acute myeloid leukemia (AML) patients who lack HLA-matched donors. Relapse after haplo-SCT remains a major concern, especially after nonmyeloablative conditioning regimens. Promising results were reported for TBF-based conditioning regimens (thiotepa, busulfan, and fludarabine) in patients transplanted from different categories of donors and for various disease types but not specifically in PT-Cy haplo-SCT for AML. Here we evaluate the outcome of 100 AML patients who received haplo-SCT with PT-Cy after TBF conditioning regimens (reduced-intensity conditioning, n = 77; myeloablative conditioning, n = 23) in 2 transplant programs. Cumulative incidences of grades III to IV acute and moderate or severe chronic graft-versus-host disease (GVHD) were 7% and 14%, respectively. NRM at 2 years was 28%, significantly influenced by disease status at haplo-SCT (first complete response [CR1] versus advanced AML: 16% versus 38%, P = .016) but not by conditioning intensity or age. The cumulative incidences of relapse at 2 years were 17% and 24% in CR1 and advanced AML, respectively (not significant). Progression-free survival, overall survival, and GVHD and relapse-free survival at 2 years were 67%, 71%, and 49% in CR1 patients, respectively, whereas comparative values in patients with advanced disease were 37%, 41%, and 32%. Our study suggests that TBF conditioning for PT-Cy haplo-SCT is safe and effective for AML patients in CR1. In patients with more advanced disease, the relatively low incidence of relapse seems counterbalanced by a high nonrelapse mortality, underlining the need for alternative strategies to decrease relapse risk, without increasing the intensity of conditioning regimen.

Original languageEnglish
Pages (from-to)1803-1809
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Volume25
Issue number9
DOIs
Publication statusPublished - Sep 2019

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    Pagliardini, T., Castagna, L., Harbi, S., Porta, M. D., Rey, J., Fürst, S., Bramanti, S., Saillard, C., Legrand, F., Maisano, V., Faucher, C., Granata, A., Hospital, M-A., Lining, W., Weiller, P-J., Calmels, B., Charbonnier, A., Lemarie, C., Chabannon, C., ... Devillier, R. (2019). Thiotepa, Fludarabine, and Busulfan Conditioning Regimen before T Cell-Replete Haploidentical Transplantation with Post-Transplant Cyclophosphamide for Acute Myeloid Leukemia: A Bicentric Experience of 100 Patients. Biology of Blood and Marrow Transplantation, 25(9), 1803-1809. https://doi.org/10.1016/j.bbmt.2019.05.014