title: FLAG (fludarabine, cytosine arabinoside, G-CSF) for refractory and relapsed acute myeloid leukemia.
abstract: Twenty-two patients with refractory or relapsed AML were treated with FLAG [25 mg/m2 fludarabine daily (days 1-5), 2 g/m2 daily Ara-C (days 1-5) and 400 micrograms/m2 daily G-CSF (day -1 till the absolute neutrophil count was > 500/microliter)]. Median age was 46 years (range 24-63). Eight patients had leukemia which was primarily refractory to conventional regimens, six were in first, seven were in second, and one was in third relapse. Overall, 11 of 22 (50%) patients achieved complete remission (CR), three had a partial response (PR), and seven did not respond (NR). One patient died of an early cerebral hemorrhage. The median remission duration from achievement of CR after FLAG was 9.9 months and median survival was 13.0 months. One patient is alive in CR at 31.9 months. Hematological toxicity of the regimen was severe. The median time to neutrophil recovery (ANC > 500/microliter) was 21 days (range 18-33). A median of seven red cell units (range 0-22) and of six platelet concentrate units (range 3-28) had to be given. Median duration of febrile neutropenia was 2 days (range 0-20 days) and patients were on i.v. antibiotics for a median of 16 days (range 0-51). There was no death from infection. Nonhematological toxicity was remarkably low, with almost no neurotoxicity and no major hepatotoxicity. In conclusion, FLAG seems to be an efficient and well tolerated regimen. It may be particularly useful for patients who have a sibling or unrelated donor for subsequent allogeneic bone marrow transplantation.
authors.affiliation: First Department of Internal Medicine, University of Vienna, Austria.
authors.forename: I M
authors.initials: IM
authors.lastname: Huhmann
authors.forename: H H
authors.initials: HH
authors.lastname: Watzke
authors.forename: K
authors.initials: K
authors.lastname: Geissler
authors.forename: H
authors.initials: H
authors.lastname: Gisslinger
authors.forename: U
authors.initials: U
authors.lastname: Jäger
authors.forename: P
authors.initials: P
authors.lastname: Knöbl
authors.forename: I
authors.initials: I
authors.lastname: Pabinger
authors.forename: L
authors.initials: L
authors.lastname: Korninger
authors.forename: C
authors.initials: C
authors.lastname: Mannhalter
authors.forename: G
authors.initials: G
authors.lastname: Mitterbauer
authors.forename: I
authors.initials: I
authors.lastname: Schwarzinger
authors.forename: P
authors.initials: P
authors.lastname: Kalhs
authors.forename: O A
authors.initials: OA
authors.lastname: Haas
authors.forename: K
authors.initials: K
authors.lastname: Lechner
mesh_terms: D000208:Acute Disease; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D002493:Central Nervous System Diseases / Q000139:chemically induced; D003561:Cytarabine / Q000627:therapeutic use / Q000633:toxicity; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use / Q000633:toxicity; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009503:Neutropenia / Q000209:etiology; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use / Q000633:toxicity; D014839:Vomiting / Q000139:chemically induced
chemical_list: D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D014740:Vidarabine