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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.
Biol Blood Marrow Transplant. 2019 09; 25(9):1803-1809.BB

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.

Authors+Show Affiliations

Department of Hematology, Institut Paoli-Calmettes, Marseille, France.Department of Hematology, Humanitas Cancer Center, Rozzano, Italy.Department of Hematology, Institut Paoli-Calmettes, Marseille, France.Department of Hematology, Humanitas Cancer Center, Rozzano, Italy.Department of Hematology, Institut Paoli-Calmettes, Marseille, France.Department of Hematology, Institut Paoli-Calmettes, Marseille, France.Department of Hematology, Humanitas Cancer Center, Rozzano, Italy.Department of Hematology, Institut Paoli-Calmettes, Marseille, France.Department of Hematology, Institut Paoli-Calmettes, Marseille, France.Department of Hematology, Institut Paoli-Calmettes, Marseille, France.Department of Hematology, Institut Paoli-Calmettes, Marseille, France.Department of Hematology, Institut Paoli-Calmettes, Marseille, France.Department of Hematology, Institut Paoli-Calmettes, Marseille, France.Department of Hematology, Shanghai Institute of Hematology, Shanghai, China.Department of Hematology, Institut Paoli-Calmettes, Marseille, France.Centre de Thérapie Cellulaire, Institut Paoli-Calmettes, Marseille, France.Department of Hematology, Institut Paoli-Calmettes, Marseille, France.Centre de Thérapie Cellulaire, Institut Paoli-Calmettes, Marseille, France.Centre de Thérapie Cellulaire, Institut Paoli-Calmettes, Marseille, France; Centre de Recherche en Cancérologie de Marseille, Inserm U1068, UMR 7258, Marseille, France; Aix-Marseille University, UM 105, Marseille, France; CIC Biothérapies, Inserm CBT-1409, Marseille, France.Department of Hematology, Institut Paoli-Calmettes, Marseille, France; Centre de Recherche en Cancérologie de Marseille, Inserm U1068, UMR 7258, Marseille, France; Aix-Marseille University, UM 105, Marseille, France.Intensive Care Unit, Institut Paoli-Calmettes, Marseille, France.Department of Hematology, Institut Paoli-Calmettes, Marseille, France; Centre de Recherche en Cancérologie de Marseille, Inserm U1068, UMR 7258, Marseille, France; Aix-Marseille University, UM 105, Marseille, France.Department of Hematology, Institut Paoli-Calmettes, Marseille, France; Centre de Recherche en Cancérologie de Marseille, Inserm U1068, UMR 7258, Marseille, France; Aix-Marseille University, UM 105, Marseille, France. Electronic address: devillierr@ipc.unicancer.fr.

Pub Type(s)

Clinical Trial
Journal Article
Multicenter Study

Language

eng

PubMed ID

31128325

Citation

Pagliardini, Thomas, et al. "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 : Journal of the American Society for Blood and Marrow Transplantation, vol. 25, no. 9, 2019, pp. 1803-1809.
Pagliardini T, Castagna L, Harbi S, et al. 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. Biol Blood Marrow Transplant. 2019;25(9):1803-1809.
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 : Journal of the American Society for Blood and Marrow Transplantation, 25(9), 1803-1809. https://doi.org/10.1016/j.bbmt.2019.05.014
Pagliardini T, et al. 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. Biol Blood Marrow Transplant. 2019;25(9):1803-1809. PubMed PMID: 31128325.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Pagliardini,Thomas, AU - Castagna,Lucas, AU - Harbi,Samia, AU - Porta,Matteo Della, AU - Rey,Jerome, AU - Fürst,Sabine, AU - Bramanti,Stefania, AU - Saillard,Colombe, AU - Legrand,Faezeh, AU - Maisano,Valerio, AU - Faucher,Catherine, AU - Granata,Angela, AU - Hospital,Marie-Anne, AU - Lining,Wang, AU - Weiller,Pierre-Jean, AU - Calmels,Boris, AU - Charbonnier,Aude, AU - Lemarie,Claude, AU - Chabannon,Christian, AU - Vey,Norbert, AU - Mokart,Djamel, AU - Blaise,Didier, AU - Devillier,Raynier, Y1 - 2019/05/22/ PY - 2019/02/11/received PY - 2019/05/10/revised PY - 2019/05/12/accepted PY - 2019/5/28/pubmed PY - 2020/7/30/medline PY - 2019/5/26/entrez KW - AML KW - Haploidentical SCT KW - Thiotepa-busulfan-fludarabine SP - 1803 EP - 1809 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol. Blood Marrow Transplant. VL - 25 IS - 9 N2 - 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. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/31128325/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(19)30325-8 DB - PRIME DP - Unbound Medicine ER -