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

Fecha de publicación: 09/01/2018

Autores de IIS La Fe

Jorge Sanz Sánchez

Autor

Participantes ajenos a IIS La Fe

Saraceni, F
Labopin, M
Hamladji, RM
Mufti, G
Socie, G
Shimoni, A
Delage, J
Deconinck, E
Chevallier, P
Blaise, D
Huynh, A
Forcade, E
Savani, BN
Mohty, M
Nagler, A
Acute Leukemia Working Party Europ

Grupos

Cardiopatías familiares, muerte súbita y mecanismos de enfermedad (CAFAMUSME)

Investigador Principal

Aitana Braza Boils

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.

Datos de la publicación

ISSN/ISSNe:: 1949-2553, 1949-2553
Tipo:: Article
Páginas:: 3379-3393
DOI:: 10.18632/oncotarget.23273
Factor de Impacto:: 1,575 SCImago ℠
Cuartil:: Q1 SCImago ℠

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Keywords

acute myeloid leukemia (AML); allogeneic transplantation; thiotepa-busulfan-fludarabine (TBF); busulfan-fludarabine (BF); myeloablative conditioning (MAC)