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

• Published in: International journal of hematology Vol. 111; no. 2; pp. 247 - 255
• Main Authors: Ueda, Tomoaki, Jo, Tomoyasu, Okada, Kazuya, Arai, Yasuyuki, Sato, Takayuki, Maeda, Takeshi, Onishi, Tatsuhito, Ueda, Yasunori
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01.02.2020; Springer Nature B.V
• Subjects: Anticancer properties; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Busulfan; Busulfan - administration & dosage; Busulfan - adverse effects; Disease control; Dosage; Fludarabine; Geriatrics; Hematology; Humans; Leukemia; Leukemia, Myeloid - drug therapy; Leukemia, Myeloid - mortality; Malignancy; Medicine; Medicine & Public Health; Melphalan; Melphalan - administration & dosage; Melphalan - adverse effects; Older people; Oncology; Original Article; Prognosis; Retrospective Studies; Stem cell transplantation; Stem cells; Survival; Survival Rate; Toxicity; Transplantation; Vidarabine - administration & dosage; Vidarabine - adverse effects; Vidarabine - analogs & derivatives; Conditioning regimen; Busulfan; Allogeneic stem cell transplantation; Myeloid malignancy; Melphalan
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-019-02763-2

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/m 2 ), MEL (100 mg/m 2 ), 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.