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Curative potential of fludarabine, melphalan, and non-myeloablative dosage of busulfan in elderly patients with myeloid malignancy

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Abstract

Although the combination of fludarabine and high-dose melphalan (FLU/MEL) has been widely used in allogeneic stem cell transplantation, high-dose MEL causes life-threatening adverse events, especially in elderly patients. To reduce the toxicity of MEL without losing its antileukemic effect, we formulated a regimen comprising FLU (125 mg/m2), MEL (100 mg/m2), and a non-myeloablative busulfan dosage [4 mg/kg orally (oral) or 3.2 mg/kg intravenously (iv); FLU/MEL/BU]. We retrospectively analyzed 32 patients with myeloid malignancies who received FLU/MEL/BU at our institute. Median age was 59 years and the median observation period after allo-SCT was 8.2 years. The disease status of most of the patients (97%) at transplantation was controlled. The rate of neutrophil engraftment was 93.3%. The 5-year overall survival (OS), disease-free survival (DFS), non-relapse mortality (NRM), and relapse rate (RR) were 68.5%, 62.1%, 22.0%, and 15.9%, respectively, in all patients. Notably, the outcome of FLU/MEL/iv BU was excellent, with the 5-year OS and DFS being 75.6% and 70.8%, respectively, accompanied by a reduced 5-year NRM and RR of 19.3% and 9.8%, respectively. In conclusion, FLU/MEL/BU, particularly FLU/MEL/iv BU, has curative potential for controlled myeloid malignancies.

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Acknowledgements

This study was conducted at Kurashiki Central Hospital’s Department of Hematology/Oncology. We would like to thank all clinicians, medical staffs, and patients who contributed to this research.

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Authors and Affiliations

  1. Department of Hematology/Oncology, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, 710-8602, Japan

    Tomoaki Ueda, Tomoyasu Jo, Kazuya Okada, Yasuyuki Arai, Takayuki Sato, Takeshi Maeda, Tatsuhito Onishi & Yasunori Ueda

  2. Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Suita, Japan

    Tomoaki Ueda

  3. Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Tomoyasu Jo & Yasuyuki Arai

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  1. Tomoaki Ueda
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Contributions

TU and YU designed the study and analyzed the data. Transplantation was performed by TU, TJ, KO, YA, TS, TM, and TO with assistance from YU. The manuscript was written by TU and YU with assistance from TJ, KO, YA, TS, TM, and TO.

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Correspondence to Tomoaki Ueda.

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Ueda, T., Jo, T., Okada, K. et al. Curative potential of fludarabine, melphalan, and non-myeloablative dosage of busulfan in elderly patients with myeloid malignancy. Int J Hematol 111, 247–255 (2020). https://doi.org/10.1007/s12185-019-02763-2

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