title: Double reinforcement with fludarabine/high-dose cytarabine enhances the impact of autologous stem cell transplantation in acute myeloid leukemia patients.
abstract: Reinforced chemotherapy based on a double high-dose consolidation regimen could be a different way to enhance in vivo purging prior to autologous stem cell transplantation (auto-SCT) in acute myeloid leukemia (AML). We investigated the impact on outcome of auto-SCT after two different strategies of early intensification performed after an identical induction regimen in adult patients with AML. Between January 1993 and December 1998, 140 consecutive AML patients were enrolled in a program consisting of an identical anthracycline-based induction (ICE) and two different consolidation regimens: one cycle, cytarabine-based (single-NOVIA: 91 patients); two cycles, fludarabine-based (double-FLAN: 49 patients). Seventy out of 91 patients received single-NOVIA consolidation: 60 underwent a transplantation procedure (allogeneic bone marrow transplantation (allo-BMT):16 patients; auto-SCT: 44). Thirty-five out of 49 patients received double-FLAN consolidation: 31 underwent a transplantation procedure (allo-BMT: 10; auto-SCT: 21). The double consolidation regimen was well-tolerated with only minor side-effects. Median follow-up observation time for surviving patients was 38 months (range, 17-71) 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 survival 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 when the patients were analyzed for intention to treat (P = 0.04). In addition, the double-FLAN consolidation group showed a superior overall survival and lower relapse rate (P = 0.02). We conclude that the double-FLAN reinforcement strategy is safe and enhances the clinical impact of auto-SCT for AML patients in first complete remission. It may provide specific clinical benefit for patients undergoing auto-SCT.
authors.affiliation: Institute of Hematology and Medical Oncology 'L and A Seragnoli', Bologna University, Bologna, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Visani
authors.forename: R M
authors.initials: RM
authors.lastname: Lemoli
authors.forename: A
authors.initials: A
authors.lastname: Isidori
authors.forename: P P
authors.initials: PP
authors.lastname: Piccaluga
authors.forename: G
authors.initials: G
authors.lastname: Martinelli
authors.forename: M
authors.initials: M
authors.lastname: Malagola
authors.forename: L
authors.initials: L
authors.lastname: Gugliotta
authors.forename: A
authors.initials: A
authors.lastname: Bonini
authors.forename: F
authors.initials: F
authors.lastname: Bonifazi
authors.forename: M R
authors.initials: MR
authors.lastname: Motta
authors.forename: S
authors.initials: S
authors.lastname: Rizzi
authors.forename: S
authors.initials: S
authors.lastname: Castellani
authors.forename: S
authors.initials: S
authors.lastname: Tura
mesh_terms: D000206:Actuarial Analysis; D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D016465:Bone Marrow Purging / Q000379:methods; D003561:Cytarabine / Q000008:administration & dosage* / Q000633:toxicity; D005047:Etoposide / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000633:toxicity; D007951:Leukemia, Myeloid / Q000150:complications / Q000401:mortality / Q000628:therapy*; D008297:Male; D008942:Mitoxantrone / Q000008:administration & dosage / Q000633:toxicity; D012074:Remission Induction; D016019:Survival Analysis; D014182:Transplantation, Autologous / Q000379:methods; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000633:toxicity
chemical_list: D003561:Cytarabine; D005047:Etoposide; D008942:Mitoxantrone; D014740:Vidarabine; C024352:fludarabine; D015255:Idarubicin