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Treosulfan, thiotepa and fludarabine conditioning regimen prior to first allogeneic stem cell transplantation in acute myeloid leukemia and high-risk myelodysplastic syndromes: a single center experience

Bone Marrow Transplantation volume 58, pages 1059–1061 (2023)Cite this article

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The ideal goal of achieving myeloablation while reducing the transplant-related mortality (TRM) incidence led to a progressive refinement of conditioning regimens for myeloid malignancies. In this scenario treosulfan, a pro-drug and structural analog of busulfan, appeared to be a promising candidate in terms of myeloablative, immunosuppressive and anti-malignancy effects, with modest organ toxicity [1]. In recent years, two phase II [2, 3] and one phase III [4] trials showed that the treosulfan-fludarabine (treo-flu) combination can retain a myeloablative effect at a reduced TRM. However, scarce data are present in literature regarding the incorporation of treosulfan in a double-alkylating regimen prior allo-HCT [5]. Here we report the experience of a single center cohort of AML and MDS patients who underwent their first allo-HCT following treosulfan-thiotepa-fludarabine (TTF) conditioning, during the years 2016–2022.

A total of 37 patients received treosulfan at 10 (T10), 12 (T12) or 14 (T14) g/m2/day per 3 days and thiotepa 5 mg/Kg/day per 1 or 2 days, based on age and fitness. Fludarabine was administered at 30 mg/m2/day for 5 days in all patients. Peripheral blood stem cells (PBSC) were the only graft source. For non-haploidentical donors, GvHD prophylaxis consisted of cyclosporine (CsA) and short-course methotrexate; anti-thymocyte globulin (ATG) was administered in matched sibling donor (MSD), matched unrelated donor (MUD) 10/10 and MUD 9/10 at 2.5, 5 and 7.5 mg/Kg, respectively. Haploidentical patients received ATG 2.5 mg/Kg, post-transplant cyclophosphamide (PTCy) 50 mg/Kg on days 3 and 4, CsA and mycophenolate mofetil from day 5.

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All data reported within the paper and further may be available upon reasonable request to the corresponding author.

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Authors and Affiliations

  1. Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy

    G. Cassanello, F. Serpenti, K. Barbullushi, V. Bellani & F. Onida

  2. IRCCS Humanitas Research Hospital – Humanitas Cancer Center, Milan, Italy

    F. Bagnoli

  3. Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    G. Saporiti, M. Goldaniga, F. Cavallaro, G. Galassi & F. Onida

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  1. G. Cassanello
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Contributions

GS, MG, FC, KB, VB, and GG followed patients in clinic. GC, FS, FB, and FO collected data, performed statistic analysis and wrote the paper. All authors revised the paper for important intellectual content and approved the final version.

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Correspondence to G. Cassanello.

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Cassanello, G., Serpenti, F., Bagnoli, F. et al. Treosulfan, thiotepa and fludarabine conditioning regimen prior to first allogeneic stem cell transplantation in acute myeloid leukemia and high-risk myelodysplastic syndromes: a single center experience. Bone Marrow Transplant 58, 1059–1061 (2023). https://doi.org/10.1038/s41409-023-02023-2

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