Double reinforcement with fludarabine/high-dose cytarabine enhances the impact of autologous stem cell transplantation in acute myeloid leukemia patients

Reinforced chemotherapy based on a double high-dose consolidation regimen c ould be a different way to enhance in vivo purging prior to autologous stem cell transplantation (auto-SCT) in acute myeloid leukemia (AML). We invest igated the impact on outcome of auto-SCT after two different strategies of early intensification performed after an identical induction regimen in adu lt patients with AML. Between January 1993 and December 1998, 140 consecuti ve AML patients were enrolled in a program consisting of an identical anthr acycline-based induction (ICE) and two different consolidation regimens: on e cycle, cytarabine-based (single-NOVIA: 91 patients); two cycles, fludarab ine-based (double-FLAN: 49 patients). Seventy out of 91 patients received s ingle-NOVIA consolidation: 60 underwent a transplantation procedure (alloge neic bone marrow transplantation (allo-BMT):16 patients; auto-SCT: 44). Thi rty-five out of 49 patients received double-FLAN consolidation: 31 underwen t a transplantation procedure (allo-BMT: 10; auto-SCT: 21). The double cons olidation regimen was well-tolerated with only minor side-effects. Median f ollow-up observation time for surviving patients was 38 months (range, 17-7 1) for the double-FLAN consolidation group and 70 months (range: 48-93) for the single-NOVIA consolidation group. Among the patients who received auto -SCT, the double consolidation strategy produced a superior disease-free su rvival curve at 36 months (78.6% (95%CI: 59.4-97.8) vs 47.7% (95%CI: 33-62. 4)) compared with the single-NOVIA group. This difference was confirmed whe n the patients were analyzed for intention to treat (P = 0.04). In addition , the double-FLAN consolidation group showed a superior overall survival an d lower relapse rate (P = 0.02). We conclude that the double-FLAN reinforce ment strategy is safe and enhances the clinical impact of auto-SCT for AML patients in first complete remission. It may provide specific clinical bene fit for patients undergoing auto-SCT.