title: Timed sequential chemotherapy for advanced acute myeloid leukemia.
abstract: Timed sequential chemotherapy (TSC) combining mitoxantrone on days 1-3, etoposide on days 8-10 and cytarabine on days 1-3 and 8-10, was administered to 240 patients with advanced acute myelogenous leukemia (AML). Sixty one percent of patients, with a 95% confidence interval (CI) ranging from 54 to 67%, achieved complete remission (CR), including 47% (CI: 38-55%) of refractory patients and 78% (CI: 70-86%) of late first relapse patients (p < 0.0001). Thirty percent of patients did not respond to therapy and 9% died from toxicity. Median duration of neutropenia was 32 days and of thrombocytopenia 29 days. Severe non hematologic toxicity included sepsis in 45% of patients and mucositis in 27%. Post-remission therapy varied but included maintenance chemotherapy in most patients, a second course of TSC in 27, autologous stem cell transplantation in 17 and allogeneic transplantation in 20. Median survival of patients who were not transplanted was 7 months with 13% (CI: 7-19%) survival at 5 years. Median disease-free survival (DFS) was 9 months with 13% (CI: 6-20%) DFS at 5 years. Previous refractoriness was the main factor associated with poor prognosis for achieving CR, DFS and survival in a multivariate analysis. There was no difference in DFS between patients receiving the different modalities of intensive post-remission therapy. These results confirm initial reports on TSC and show that some patients with first relapse off therapy can enjoy prolonged DFS using chemotherapy only.
authors.affiliation: Service d'Hématologie, Hôpital Edouard Herriot, Lyon, France.
authors.forename: E
authors.initials: E
authors.lastname: Archimbaud
authors.forename: V
authors.initials: V
authors.lastname: Leblond
authors.forename: P
authors.initials: P
authors.lastname: Fenaux
authors.forename: H
authors.initials: H
authors.lastname: Dombret
authors.forename: C
authors.initials: C
authors.lastname: Cordonnier
authors.forename: F
authors.initials: F
authors.lastname: Dreyfus
authors.forename: P
authors.initials: P
authors.lastname: Cony-Makhoul
authors.forename: H
authors.initials: H
authors.lastname: Tilly
authors.forename: X
authors.initials: X
authors.lastname: Troussard
authors.forename: G
authors.initials: G
authors.lastname: Auzanneau
authors.forename: X
authors.initials: X
authors.lastname: Thomas
authors.forename: M
authors.initials: M
authors.lastname: Ffrench
authors.forename: J P
authors.initials: JP
authors.lastname: Marie
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage* / Q000627:therapeutic use; D003630:Daunorubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D005047:Etoposide / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D003561:Cytarabine; D005047:Etoposide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D008942:Mitoxantrone; D003630:Daunorubicin