Reduced-intensity fludarabine/melphalan confers similar survival to busulfan/fludarabine myeloablative regimens for patients with acute myeloid leukemia and myelodysplasia

Abstract

Optimal conditioning chemotherapy for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) remains uncertain. Myeloablative regimens such as fludarabine/busulfan are favored over reduced-intensity fludarabine/melphalan (Flu/Mel); however, it is not known if Flu/Mel is inferior. We analyzed hematopoietic cell transplantation recipients with AML and MDS who received fludarabine with once-daily intravenous busulfan targeted to either area under the curve (AUC) 5300 µM*L/min (Flu/Bu 5300) (n = 246) or AUC 3500 µM*L/min (Flu/Bu 3500) (n = 81), or Flu/Mel (n = 69). Flu/Bu regimens were compared separately to Flu/Mel. After 2-year follow-up, no differences in overall or relapse-free survival were found between Flu/Bu 5300 or 3500 versus Flu/Mel though relapse rates were significantly higher; 33.1% (p = 0.024), 44.6% (p = 0.002), versus 19.4%, respectively. Flu/Bu 5300 (p = 0.008) and Flu/Bu 3500 (p < 0.001) groups were prognostic for relapse compared to Flu/Mel. Flu/Mel yields lower relapse rates and similar survival benefit when compared to Flu/Bu 3500 or 5300 µM*L/min.

Keywords: Fludarabine; acute myeloid leukemia; busulfan; melphalan; myelodysplastic syndrome.

Conflict of interest statement

Disclosure statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.

(A) Overall survival plot of fludarabine and busulfan 5300 compared with fludarabine and melphalan. (B) Overall survival plot of fludarabine and busulfan 3500 compared with fludarabine and melphalan.

Figure 2.

(A) Cumulative incidence of relapse plot of fludarabine and busulfan 5300 compared with fludarabine and melphalan. (B) Cumulative incidence of relapse plot of fludarabine and busulfan 3500 compared with fludarabine and melphalan.

Figure 3.

(A) Non-relapse mortality plot of fludarabine and busulfan 5300 compared with fludarabine and melphalan. (B) Non-relapse mortality plot of fludarabine and busulfan 3500 compared with fludarabine and melphalan.