Jean El-Cheikh1, Myriam Labopin2, Farouk Al-Chami3, Ali Bazarbachi3, Emanuele Angelucci4, Stella Santarone5, Francesca Bonifazi6, Angelo Michele Carella7, Luca Castagna8, Benedetto Bruno9, Anna Paola Iori10, Giorgio La Nasa11, Bipin Savani12, Arnon Nagler13, Mohamad Mohty14. 1. American University of Beirut Medical Center, Beirut, Lebanon. Electronic address: je46@aub.edu.lb. 2. European Society for Blood and Marrow Transplantation Paris Study Office/CEREST-TC, Paris, France. 3. American University of Beirut Medical Center, Beirut, Lebanon. 4. Hematology and Transplant Center, IRCCS Ospedale Policlinico San Martino, Genova, Italy. 5. Ospedale Civile Dipartimento di Ematologia, Medicina Trasfusionale e Biotecnologie, Pescara, Italy. 6. S.Orsola-Malpighi University Hospital, Institute of Hematology and Medical, Oncology L and A Seràgnoli, Bologna, Italy. 7. IRCCS, Casa Sollievo della Sofferenza, Department of Hemato-Oncology Stem Cell Transplant Unit, SGiovanni Rot, Italy. 8. Istituto Clinico Humanitas, Transplantation Unit, Department of Oncology and Haematology, Milano, Italy. 9. S.S.C.V.D Trapianto di Cellule Staminali, A.O.U Citta della Salute e della Scienza di Torino Presidio Molinette, Torino, Italy. 10. Univ. La Sapienza, Dip. Biotecnologie Cellulari ed Ematologia, Rome, Italy. 11. Centro Trapianti Unico Di CSE Adulti e Pediatrico A. O Brotzu, Cagliari, Italy. 12. Vanderbilt University Medical Center, Nashville, TN. 13. Chaim Sheba Medical Center, Tel-Hashomer, Israel. 14. Hopital Saint Antoine, Department of Hematology, Paris, France.
Abstract
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.
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.
Authors: Jesús Duque-Afonso; Gabriele Ihorst; Miguel Waterhouse; Robert Zeiser; Ralph Wäsch; Hartmut Bertz; Mehtap Yücel; Thomas Köhler; Joachim Müller-Quernheim; Reinhard Marks; Jürgen Finke Journal: Bone Marrow Transplant Date: 2020-06-26 Impact factor: 5.483