Thiotepa-busulfan-fludarabine compared to busulfan-fludarabine for sibling and unrelated donor transplant in acute myeloid leukemia in first remission

// Francesco Saraceni 1 , Myriam Labopin 2 , Rose-Marie Hamladji 3 , Ghulam Mufti 4 , Gerard Socié 5 , Avichai Shimoni 6 , Jeremy Delage 7 , Eric Deconinck 8 , Patrice Chevallier 9 , Didier Blaise 10 , Jaime Sanz 11 , Anne Huynh 12 , Edouard Forcade 13 , Bipin N. Savani 14 , Mohamad Mohty 15 , Arnon Nagler 2, 6 and Acute Leukemia Working Party of the European society for Blood and Marrow Transplantation (EBMT) 1 Hematology and Stem Cell Transplant, Ravenna Hospital, Ravenna, Italy 2 EBMT Paris Study Office, Saint Antoine Hospital, Paris, France 3 Centre Pierre et Marie Curie, Service Hématologie Greffe de Moëlle, Alger, Algeria 4 GKT School of Medicine, Department of Haematological Medicine, London, United Kingdom 5 Hopital St. Louis, Department of Hematology-BMT, Paris, France 6 Chaim Sheba Medical Center, Department of Bone Marrow Transplantation, Tel-Hashomer, Israel 7 CHU Lapeyronie, Département d’Hématologie Clinique, Montpellier, France 8 Hopital Jean Minjoz, Service d’Hématologie, Besançon, France 9 CHU Nantes, Department D’Hématologie, Nantes, France 10 Programme de Transplantation and Therapie Cellulaire, Centre de Recherche en Cancérologie de Marseille, Institut Paoli Calmettes, Marseille, France 11 Hospital Universitario La Fe, Servicio de Hematologia, Valencia, Spain 12 Institut Universitaire du Cancer Toulouse, Oncopole, I.U.C.T-O, Toulouse, France 13 CHU Bordeaux, Hôpital Haut-Leveque, Pessac, France 14 Vanderbilt University Medical Center, Nashville, TN, USA 15 Department of Haematology, Saint Antoine Hospital, Paris, France Correspondence to: Francesco Saraceni, email: francesco.saraceni@libero.it Keywords: acute myeloid leukemia (AML); allogeneic transplantation; thiotepa-busulfan-fludarabine (TBF); busulfan-fludarabine (BF); myeloablative conditioning (MAC) Received: October 17, 2017      Accepted: November 20, 2017      Published: December 15, 2017 ABSTRACT Background: A preparatory regimen consisting of thiotepa-busulfan-fludarabine (TBF) has been associated with reduced relapse in patients with haematological malignancies after haploidentical and cord blood transplants; however, few data exist regarding TBF conditioning in sibling (MSD) and unrelated donor (URD) transplants for AML. Results: Among patients receiving a myeloablative (MAC) regimen, TBF-MAC was associated with significantly lower relapse (HR 0.47, p = 0.005) however higher non-relapse mortality (NRM, HR 2.69, p < 10 –4 ) as compared to BF. This led to similar leukemia-free (LFS) and overall survival (OS) between the two regimens (LFS: p = 0.6; OS: p = 0.27). When we selected TBF-MAC patients receiving busulfan 9.6 mg/kg, NRM resulted still higher but no more significantly different as compared to BF-MAC with busulfan 12.8 mg/kg (HR 1.53, p = 0.12); despite the lower busulfan dose, relapse remained inferior with TBF-MAC (HR 0.45, p = 0.01), however no difference in survival could be demonstrated (LFS: p = 0.31; OS: 0.82). Among patients receiving a reduced-intensity (RIC) regimen, similar outcome was observed with TBF-RIC and BF-RIC (LFS: p = 0.77; OS: p = 0.88). Conclusions: TBF-MAC as conditioning regimen for transplant from MSD and URD in AML patients in first remission provided stronger anti-leukemic activity but higher NRM as compared to BF-MAC, thus leading to similar survival. TBF-MAC with busulfan 9.6 mg/kg was associated with low relapse and acceptable NRM, however again with no survival benefit. TBF-RIC and BF-RIC resulted in comparable outcome. Methods: We conducted a registry-based study comparing outcomes of patients with AML in first remission undergoing transplant from MSD or URD prepared with either TBF ( n = 212) or BF ( n = 2698) conditioning.