Effect of the Thiotepa Dose in the TBF Conditioning Regimen in Patients Undergoing Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia in Complete Remission: A Report From the EBMT Acute Leukemia Working Party.


Journal

Clinical lymphoma, myeloma & leukemia
ISSN: 2152-2669
Titre abrégé: Clin Lymphoma Myeloma Leuk
Pays: United States
ID NLM: 101525386

Informations de publication

Date de publication:
05 2020
Historique:
received: 21 11 2019
revised: 13 01 2020
accepted: 17 01 2020
pubmed: 23 2 2020
medline: 2 6 2021
entrez: 22 2 2020
Statut: ppublish

Résumé

Allogeneic stem cell transplantation is a potentially curative therapy for patients with acute myeloid leukemia (AML) after achieving complete remission (CR). The aim of this study is to evaluate the optimal dose of thiotepa, administered as part of the thiotepa-busulfan-fludarabine (TBF) conditioning regimen for allogeneic stem cell transplantation in adults with AML in CR. In a retrospective multicenter analysis, we identified 240 patients allotransplanted from matched related or unrelated donors or T replete haplo-identical donors. We compared the transplantation outcomes of patients who received 5 mg/kg thiotepa and 2 days of intravenous busulfan at 6.4 mg/kg (T1B2F) versus those who received 10 mg/kg thiotepa with 2 days of intravenous busulfan at 6.4 mg/kg (T2B2F). The median follow-up was 20 months. On univariate analysis, the incidence of acute graft versus host disease (GVHD) grade II to IV was significantly lower in the T1B2F group (19%) versus 32% in the T2B2F group (P = .029). This result was confirmed on multivariate analysis; acute GVHD was higher for patients receiving T2B2F (hazard ratio, 2.22; P = .024). No significant change in non-relapse mortality, progression-free survival, or overall survival was observed between the 2 groups. T2B2F is associated with a higher incidence of acute GVHD compared with T1B2F. These results suggest that a lower dose-intensity of thiotepa and busulfan in the TBF regimen may yield better results in patients with AML in CR.

Sections du résumé

BACKGROUND
Allogeneic stem cell transplantation is a potentially curative therapy for patients with acute myeloid leukemia (AML) after achieving complete remission (CR). The aim of this study is to evaluate the optimal dose of thiotepa, administered as part of the thiotepa-busulfan-fludarabine (TBF) conditioning regimen for allogeneic stem cell transplantation in adults with AML in CR.
PATIENTS AND METHODS
In a retrospective multicenter analysis, we identified 240 patients allotransplanted from matched related or unrelated donors or T replete haplo-identical donors. We compared the transplantation outcomes of patients who received 5 mg/kg thiotepa and 2 days of intravenous busulfan at 6.4 mg/kg (T1B2F) versus those who received 10 mg/kg thiotepa with 2 days of intravenous busulfan at 6.4 mg/kg (T2B2F). The median follow-up was 20 months.
RESULTS
On univariate analysis, the incidence of acute graft versus host disease (GVHD) grade II to IV was significantly lower in the T1B2F group (19%) versus 32% in the T2B2F group (P = .029). This result was confirmed on multivariate analysis; acute GVHD was higher for patients receiving T2B2F (hazard ratio, 2.22; P = .024). No significant change in non-relapse mortality, progression-free survival, or overall survival was observed between the 2 groups.
CONCLUSION
T2B2F is associated with a higher incidence of acute GVHD compared with T1B2F. These results suggest that a lower dose-intensity of thiotepa and busulfan in the TBF regimen may yield better results in patients with AML in CR.

Identifiants

pubmed: 32081702
pii: S2152-2650(20)30044-6
doi: 10.1016/j.clml.2020.01.007
pii:
doi:

Substances chimiques

Thiotepa 905Z5W3GKH
Vidarabine FA2DM6879K
Busulfan G1LN9045DK
fludarabine P2K93U8740

Types de publication

Clinical Trial Journal Article Multicenter Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

296-304

Informations de copyright

Copyright © 2020 Elsevier Inc. All rights reserved.

Auteurs

Jean El-Cheikh (J)

American University of Beirut Medical Center, Beirut, Lebanon. Electronic address: je46@aub.edu.lb.

Myriam Labopin (M)

European Society for Blood and Marrow Transplantation Paris Study Office/CEREST-TC, Paris, France.

Farouk Al-Chami (F)

American University of Beirut Medical Center, Beirut, Lebanon.

Ali Bazarbachi (A)

American University of Beirut Medical Center, Beirut, Lebanon.

Emanuele Angelucci (E)

Hematology and Transplant Center, IRCCS Ospedale Policlinico San Martino, Genova, Italy.

Stella Santarone (S)

Ospedale Civile Dipartimento di Ematologia, Medicina Trasfusionale e Biotecnologie, Pescara, Italy.

Francesca Bonifazi (F)

S.Orsola-Malpighi University Hospital, Institute of Hematology and Medical, Oncology L and A Seràgnoli, Bologna, Italy.

Angelo Michele Carella (AM)

IRCCS, Casa Sollievo della Sofferenza, Department of Hemato-Oncology Stem Cell Transplant Unit, SGiovanni Rot, Italy.

Luca Castagna (L)

Istituto Clinico Humanitas, Transplantation Unit, Department of Oncology and Haematology, Milano, Italy.

Benedetto Bruno (B)

S.S.C.V.D Trapianto di Cellule Staminali, A.O.U Citta della Salute e della Scienza di Torino Presidio Molinette, Torino, Italy.

Anna Paola Iori (AP)

Univ. La Sapienza, Dip. Biotecnologie Cellulari ed Ematologia, Rome, Italy.

Giorgio La Nasa (G)

Centro Trapianti Unico Di CSE Adulti e Pediatrico A. O Brotzu, Cagliari, Italy.

Bipin Savani (B)

Vanderbilt University Medical Center, Nashville, TN.

Arnon Nagler (A)

Chaim Sheba Medical Center, Tel-Hashomer, Israel.

Mohamad Mohty (M)

Hopital Saint Antoine, Department of Hematology, Paris, France.

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