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Sequential treatment with FLAG-IDA/treosulfan conditioning regimen for patients with active acute myeloid leukemia

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Abstract

Sequential protocols combining salvage chemotherapy with reduced intensity conditioning (RIC) and allogeneic hematopoietic cell transplantation (alloHCT) for high-risk acute myeloid leukemia (AML) have been studied more than a decade. Purpose of this retrospective analysis was to evaluate the anti-leukemic efficacy and toxicity of FLAG-IDA protocol (fludarabine, cytarabine, and idarubicin) followed by treosulfan-based conditioning for patients with active AML. From January 2014 to November 2019, a total of 29 active AML patients [median age, 64 years (range, 23–73)] were treated. All patients completed protocol regimen and were transplanted. Five patients (17%) had grade 3–4 toxicities; therefore, treosulfan was substituted with total body irradiation (TBI) non-myeloablative conditioning. Six (20%) patients died within 30 post-transplant days, all from infectious complications. Out of 23 evaluable patients on day 30, 22 (96%) achieved complete hematologic remission with full donor chimerism. Non-relapse mortality (NRM) rates at 1 and 3 years were 22% and 49%, respectively. Median overall survival (OS) was 12 (95% CI, 4–20) months. OS and disease-free survival were 50% and 46% at 1 year and 28% and 17% at 2 years, respectively. Age, gender, disease burden, number of previous lines, and comorbidity score did not predict survival. Sequential strategy combining FLAG-IDA and treosulfan may offer a salvage option for few selected patients with active AML; however, high NRM presents a major obstacle to treatment success. Future efforts should focus on reducing NRM by moderating regimen intensity and by better selection of patients.

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Author notes

  1. Liat Shargian-Alon and Ofir Wolach contributed equally to this work.

Authors and Affiliations

  1. Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital, 49100, Petah-Tikva, Israel

    Liat Shargian-Alon, Ofir Wolach, Uri Rozovski, Michal Sela-Navon, Mazal Rubinstein, Oren Pasvolsky, Pia Raanani & Moshe Yeshurun

  2. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Liat Shargian-Alon, Ofir Wolach, Uri Rozovski, Dafna Yahav, Nino Oniashvilli, Oren Pasvolsky, Pia Raanani & Moshe Yeshurun

  3. Infectious Disease Unit, Rabin Medical Center, Petah-Tikva, Israel

    Dafna Yahav

  4. The Raphael Recanati Genetic Institute, Rabin Medical Center, Petah-Tikva, Israel

    Nino Oniashvilli

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  1. Liat Shargian-Alon
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  2. Ofir Wolach
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Correspondence to Liat Shargian-Alon.

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Shargian-Alon, L., Wolach, O., Rozovski, U. et al. Sequential treatment with FLAG-IDA/treosulfan conditioning regimen for patients with active acute myeloid leukemia. Ann Hematol 99, 2939–2945 (2020). https://doi.org/10.1007/s00277-020-04232-x

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