International Journal of Hematology

DOI: 10.1007/s12185-018-2562-8 Pages: 1-9

Addition of melphalan to fludarabine/busulfan (FLU/BU4/MEL) provides survival benefit for patients with myeloid malignancy following allogeneic bone-marrow transplantation/peripheral blood stem-cell transplantation

1. Osaka University Graduate School of Medicine, Department of Hematology and Oncology

2. Osaka University Hospital, Department of Blood Transfusion

Correspondence to:
Tomoaki Ueda
Tel: +81-6-6879-3871
Email: uedat@bldon.med.osaka-u.ac.jp

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Abstract

A conditioning regimen with fludarabine and myeloablative dose of busulfan (FLU/BU4) has been commonly used in allogeneic hematopoietic cell transplantation (allo-HCT). However, there are two major problems with this regimen: insufficient anti-leukemic effect, especially in advanced cases, and slow time to complete donor-type chimerism, especially T-cell chimerism. To overcome these issues, we designed a combination regimen with FLU (150 mg/m2), intravenous BU (12.8 mg/kg), and melphalan (100 mg/m2) (FLU/BU4/MEL) and conducted retrospective analyses of treatment outcomes at our institute. Forty-two patients with myeloid malignancies received allogeneic bone-marrow transplantation or peripheral blood stem-cell transplantation (allo-BMT/PBSCT) with FLU/BU4/MEL regimen. The median age of patients was 46.5 years (20–63 years). Thirteen patients (31%) did not achieve complete hematological remission at transplantation. All patients examined achieved complete whole and T-cell chimerism within 1 month after allo-HCT. The 4-year overall survival and disease-free survival rates were 66.0% [95% confidence interval (CI) 49.4–78.3%] and 59.5% (95% CI 43.2–72.6%) in all patients, and 49.4% (95% CI 19.7–73.6%) and 38.5% (95% CI 14.1–62.8%) in patients who were not in remission. In conclusion, FLU/BU4/MEL showed curative potential, even in patients with advanced myeloid malignancies, accompanied by achievement of rapid complete chimerism after allo-BMT/PBSCT.

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