Curative potential of fludarabine, melphalan, and non-myeloablative dosage of busulfan in elderly patients with myeloid
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ORIGINAL ARTICLE
Curative potential of fludarabine, melphalan, and non‑myeloablative dosage of busulfan in elderly patients with myeloid malignancy Tomoaki Ueda1,2 · Tomoyasu Jo1,3 · Kazuya Okada1 · Yasuyuki Arai1,3 · Takayuki Sato1 · Takeshi Maeda1 · Tatsuhito Onishi1 · Yasunori Ueda1 Received: 13 July 2019 / Revised: 15 October 2019 / Accepted: 16 October 2019 © Japanese Society of Hematology 2019
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. Keywords Allogeneic stem cell transplantation · Conditioning regimen · Myeloid malignancy · Busulfan · Melphalan
Introduction Although the combination of fludarabine plus high-dose (140–180 mg/m2) melphalan (FLU/MEL) has been widely used as a reduced-intensity conditioning regimen for myeloid malignancies [1–4], high-dose MEL occasionally causes severe mucositis, especially in elderly patients [2, 5–7]. Because mucositis adversely affects clinical outcomes, particularly infection [8, 9], reduction of MEL toxicity is desirable. To reduce the toxicity of MEL without losing its antileukemic effect, we designed a regimen comprising FLU (125 mg/m2), MEL (100 mg/m2), and a non-myeloablative
dosage of busulfan [BU; 4 mg/kg orally (oral) or 3.2 mg/kg intravenously (iv); FLU/MEL/BU]. In this regimen, instead of reducing the dose of MEL, a non-myeloablative dosage of BU was added, because non-myeloablative dosages of BU could reduce the frequency of non-relapse mortality (NRM) without the loss of antileukemic effect in elderly patients with controlled myeloid malignancies [10]. In this study, we retrospectively analyzed the efficacy and safety of FLU/MEL/BU in elderly patients with myeloid malignancies in stable disease status after a long period. We found promising long-term efficacy of FLU/MEL/BU, particularly FLU/MEL/iv BU, as a novel reduced-intensit
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