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
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.
KeywordsAllogeneic bone-marrow transplantation/peripheral blood stem-cell transplantation Conditioning regimen Myeloid malignancy Intravenous busulfan Melphalan
This study was conducted at the Department of Hematology and Oncology, Osaka University Hospital. We would like to thank all clinicians and patients who contributed to this research. Funding was provided by Otsuka Pharmaceutical (Grant no. 12908149).
TU and TM designed the study and analyzed the data. Transplantation was performed by TU, TM, SK, JF, and KF with assistance from TY, HS, YT, and YK. The manuscript was written by TU, TM, TY, and YK with assistance from KF, JF, HS, and YT.
Compliance with ethical standards
Conflict of interest
The authors received research funding from Otsuka Pharmaceutical Co., Ltd.
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