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, 3 Rose-Marie Hamladji 4 Ghulam Mufti 5 Gerard Socie 6 Avichai Shimoni 7 Jeremy Delage 8, 9 Eric Deconinck 10 Patrice Chevallier 11, 12, 13 Didier Blaise 14, 15 Jaime Sanz 16 Anne Huynh 17 Edouard Forcade 18 Bipin N. Savani Mohamad Mohty 19 Arnon Nagler 20 Acute Leukemia Working Party Europ
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.
Document type :
Journal articles
Complete list of metadatas

https://hal-amu.archives-ouvertes.fr/hal-02143546
Contributor : Ghislain Bidaut <>
Submitted on : Wednesday, May 29, 2019 - 2:47:00 PM
Last modification on : Friday, January 10, 2020 - 9:10:18 PM

Links full text

Identifiers

Citation

Francesco Saraceni, Myriam Labopin, Rose-Marie Hamladji, Ghulam Mufti, Gerard Socie, et al.. Thiotepa-busulfan-fludarabine compared to busulfan-fludarabine for sibling and unrelated donor transplant in acute myeloid leukemia in first remission. Oncotarget, Impact journals, 2018, 9 (3), pp.3379-3393. ⟨10.18632/oncotarget.23273⟩. ⟨hal-02143546⟩

Share

Metrics

Record views

59