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Research Papers:

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

Francesco Saraceni _, Myriam Labopin, Rose-Marie Hamladji, Ghulam Mufti, Gerard Socié, Avichai Shimoni, Jeremy Delage, Eric Deconinck, Patrice Chevallier, Didier Blaise, Jaime Sanz, Anne Huynh, Edouard Forcade, Bipin N. Savani, Mohamad Mohty, Arnon Nagler and Acute Leukemia Working Party of the European society for Blood and Marrow Transplantation (EBMT)

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Oncotarget. 2018; 9:3379-3393. https://doi.org/10.18632/oncotarget.23273

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Abstract

Francesco Saraceni1, Myriam Labopin2, Rose-Marie Hamladji3, Ghulam Mufti4, Gerard Socié5, Avichai Shimoni6, Jeremy Delage7, Eric Deconinck8, Patrice Chevallier9, Didier Blaise10, Jaime Sanz11, Anne Huynh12, Edouard Forcade13, Bipin N. Savani14, Mohamad Mohty15, Arnon Nagler2,6 and Acute Leukemia Working Party of the European society for Blood and Marrow Transplantation (EBMT)

1Hematology and Stem Cell Transplant, Ravenna Hospital, Ravenna, Italy

2EBMT Paris Study Office, Saint Antoine Hospital, Paris, France

3Centre Pierre et Marie Curie, Service Hématologie Greffe de Moëlle, Alger, Algeria

4GKT School of Medicine, Department of Haematological Medicine, London, United Kingdom

5Hopital St. Louis, Department of Hematology-BMT, Paris, France

6Chaim Sheba Medical Center, Department of Bone Marrow Transplantation, Tel-Hashomer, Israel

7CHU Lapeyronie, Département d’Hématologie Clinique, Montpellier, France

8Hopital Jean Minjoz, Service d’Hématologie, Besançon, France

9CHU 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

11Hospital Universitario La Fe, Servicio de Hematologia, Valencia, Spain

12Institut Universitaire du Cancer Toulouse, Oncopole, I.U.C.T-O, Toulouse, France

13CHU Bordeaux, Hôpital Haut-Leveque, Pessac, France

14Vanderbilt University Medical Center, Nashville, TN, USA

15Department of Haematology, Saint Antoine Hospital, Paris, France

Correspondence to:

Francesco Saraceni, email: [email protected]

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.


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