title: Salvage therapy for acute myeloid leukemia with fludarabine, cytarabine, and idarubicin with or without gemtuzumab ozogamicin and with concurrent or sequential G-CSF.
abstract: The current salvage therapies for relapsed/refractory acute myeloid leukemia (AML) are unsatisfactory. Over the past 7 years, we have used two salvage regimens: fludarabine, cytarabine, and idarubicin with (FLAG-IM) or without gemtuzumab ozogamicin (GO) (9 mg/m(2) on Day 8) (FLAG-I) in relapsed/refractory AML. Three-quarters of patients also received concurrent G-CSF. Seventy-one patients were treated, 23 with FLAG-I and 48 with FLAG-IM. The median duration of follow-up was 30.6 months. The treatment groups were well balanced with median ages of 48 years (range 18-70) and 47 years (range 20-68), unfavorable cytogenetics in 57% and 35%, prior allogeneic stem cell transplant in 43% and 42%, and CR1 duration <1 year in 60% and 67%, respectively, for FLAG-I and FLAG-IM. The complete remission (CR) rate in the FLAG-I group was 39% with an additional 13% achieving a CRp [overall response rate (ORR) 52%]; the CR rate in the FLAG-IM group was 29% with an additional 27% achieving a CRp (ORR 56%). The median duration of response (DOR; 16.8 vs. 8.3 months), event-free survival (EFS; 7.4 vs. 4.1 months), and overall survival (OS; 8.8 vs. 5.0 months) trended to favor FLAG-I over FLAG-IM. The patients who received G-CSF concurrent with chemotherapy had superior overall response rate (ORR; 62% vs. 29%, P = 0.026), median EFS (6.2 vs. 3.4 months, P = 0.010), and OS (8.8 vs. 3.9 months, P = 0.004) when compared with those who sequentially received G-CSF and chemotherapy, regardless of chemotherapy regimen. The addition of GO, at this dose and schedule, to FLAG-I failed to improve the outcomes in patients with relapsed/refractory AML. The patients who received G-CSF concurrently with chemotherapy had improved outcomes. Am. J. Hematol., 2009. (c) 2009 Wiley-Liss, Inc.
authors.affiliation: Section of Leukemia and Bone Marrow Transplantation, Division of Oncology, Washington University School of Medicine, Saint Louis, Missouri, USA.
authors.forename: Mike G
authors.initials: MG
authors.lastname: Martin
authors.forename: Kristan M
authors.initials: KM
authors.lastname: Augustin
authors.forename: Geoffrey L
authors.initials: GL
authors.lastname: Uy
authors.forename: John S
authors.initials: JS
authors.lastname: Welch
authors.forename: Lindsay
authors.initials: L
authors.lastname: Hladnik
authors.forename: Sagun
authors.initials: S
authors.lastname: Goyal
authors.forename: Divya
authors.initials: D
authors.lastname: Tiwari
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Monahan
authors.forename: Richard M
authors.initials: RM
authors.lastname: Reichley
authors.forename: Amanda F
authors.initials: AF
authors.lastname: Cashen
authors.forename: Keith
authors.initials: K
authors.lastname: Stockerl-Goldstein
authors.forename: Peter
authors.initials: P
authors.lastname: Westervelt
authors.forename: Camille N
authors.initials: CN
authors.lastname: Abboud
authors.forename: John F
authors.initials: JF
authors.lastname: Dipersio
authors.forename: Ravi
authors.initials: R
authors.lastname: Vij
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000617:Aminoglycosides / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003561:Cytarabine / Q000008:administration & dosage; D004341:Drug Evaluation; D005260:Female; D000079982:Gemtuzumab; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods*; D016019:Survival Analysis; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D000079982:Gemtuzumab; D014740:Vidarabine; C024352:fludarabine; D015255:Idarubicin