Feasibility of thiotepa addition to the fludarabine-busulfan conditioning with tacrolimus/sirolimus as graft vs host disease prophylaxis

Abstract

In classical reduced-intensity conditioning (RIC) regimens, including the fludarabine and busulphan (BF) combination, sirolimus and tacrolimus (SIR-TAC) as graft vs host disease (GVHD) prophylaxis has shown acceptable results. The outcomes of SIR-TAC in a more intense RIC regimen as Thiotepa-fludarabine-busulfan (TBF) have been hardly investigated. This retrospective study included all consecutive patients receiving an allogeneic hematopoietic stem cell transplantation for myeloid malignancies (January 2009–2017) conditioned with either TBF or BF and receiving SIR-TAC. Patients receiving TBF presented higher non-relapse mortality (31.6 vs 12.3%, p = .01), along with shorter overall survival (51.8% vs 77.8%, p < .01) at 2 years than patients treated with BF. There were no significant differences in the cumulative incidence of grade II–IV acute GVHD or moderate-severe chronic GVHD or relapse between both groups. These results suggest that TBF does not seem to improve the traditional RIC BF regimen, at least when associated with SIR-TAC prophylaxis.

Keywords:

• Thiotepa-fludarabine-busulfan
• sirolimus and tacrolimus
• allogeneic hematopoietic cell transplantation
• reduce intensity conditioning
• graft vs host disease prophylaxis

Acknowledgments

We thank all the authors for participating in the research.

Disclosure statement

MLF declares travel Expenses by Adienne. No other conflict of interest relevant to this study. P.B. declares have received honoraria from Amgen, Celgene, Gilead, Incyte, Jazz Pharmaceuticals, MSD, Novartis, Pfizer and Roche, not related to the present article. IG-C declares travel Expenses: Gilead, Amgen and Merck. JLP received advisory support for preclinical/clinical research and financial support to attend to the Spanish Hematology Society annual meeting 2018 and the EBMT annual meeting 2019, both from Merck and Sharp Dohme pharmaceutics. GO declares travel Expenses by Adienne. JCHB declares travel expenses by Incyte. DV received honoraria from Celgene, Amgen, Gilead, Incyte, Jazz Pharmaceuticals, MSD, Novartis, Pfizer and Addiene. No other conflict of interest relevant to this study.

CS received fundings from the Carlos III FIS PI12/01466 Health Institute. C.S. declares have received honoraria from Amgen, Celgene, Gilead, Incyte, Jazz Pharmaceuticals, MSD, Novartis, Adienne, Pfizer and Astellas, not related to the present article. FB declares honoraria from Hoffmann La Roche, Janssen, Acerta, Kite, Novartis, Abbvie, Takeda, and Celgene.

All the rest of the authors declare no conflicts of interest relevant to this study.

Author contributions

MLF designed, performed, and coordinated the research, collected, analyzed, interpreted the data, and wrote the manuscript. PB and DV designed, interpreted the data, revised the final version of this manuscript critically. IGC, APM and ABV collected data and commented on the manuscript. GVJ performed statistical analyses, produced the figures, contributed data and commented on the manuscript. JLP, GO, JM, ER, RM, OS, SS, JCHB, AE, JS, JS, CS, contributed data and commented on the manuscript. FB revised the final version of this manuscript critically.

Additional information

Funding

PB received research funding from “Instituto de Salud Carlos III” (PI16/01433), Departament de Salut, Generalitat de Catalunya (PERIS2018-2020 BDNS357800) and Asociación Española Contra el Cáncer-Ideas Semilla 2019 grant. FB received research funding from “Instituto de Salud Carlos III” PI12/01466.