title: Cytoprotection in acute myelogenous leukemia (AML) therapy.
abstract: Planning therapy for acute myelogenous leukemia (AML) is difficult because of the heterogeneous nature of the disease and varying patient age at presentation. Cytogenetics and patient age at the time of diagnosis are two major factors determining treatment outcome in AML. Patients with poor-risk cytogenetics have much lower complete remission rates than other groups. In addition, AML in patients greater than 55 to 60 years of age often exhibits a resistant phenotype, more akin to secondary AML or AML arising from myelodysplastic syndromes. This group is also characterized by lower complete remission rates, and often requires the delivery of intensive therapy to a patient population that is the least likely to tolerate it. At the Jefferson Health System (Philadelphia, PA), we wished to develop a regimen that was maximally intensive to treat stubborn disease, but gentle enough to be given to all patients regardless of age. Toward this end, 33 patients received a maximal dose of the cytoprotective agent, amifostine, before each infusion of idarubicin in the "7 + 3" regimen, escalating the dose of idarubicin in a phase I fashion to a maximum dose of 24 mg/m2 . The data indicate that the addition of amifostine to "7 + 3" AML induction therapy enables a substantial escalation of the idarubicin dose through the 21-mg/m2 dose level, without a concomitant increase in side effects, thus providing a regimen that is both intensive and applicable to patients of all ages. Currently, phase II studies are ongoing on a national basis to evaluate the efficacy of this regimen.
authors.affiliation: Thomas Jefferson Health System, Blood and Marrow Transplant Program, Philadelphia, PA 19107, USA. l_grosso@lac.jci.tju.edu
authors.forename: Dolores
authors.initials: D
authors.lastname: Grosso
authors.forename: Joanne
authors.initials: J
authors.lastname: Filicko
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Frank
authors.initials: F
authors.lastname: Beardell
authors.forename: Janet
authors.initials: J
authors.lastname: Brunner
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Cohn
authors.forename: Andres
authors.initials: A
authors.lastname: Ferbér
authors.forename: José
authors.initials: J
authors.lastname: Martinez
authors.forename: Bijoyesh
authors.initials: B
authors.lastname: Mookerjee
authors.forename: Lewis
authors.initials: L
authors.lastname: Rose
authors.forename: David
authors.initials: D
authors.lastname: Tice
authors.forename: John L
authors.initials: JL
authors.lastname: Wagner
authors.forename: Robert
authors.initials: R
authors.lastname: Capizzi
authors.forename: Neal
authors.initials: N
authors.lastname: Flomenberg
mesh_terms: D000328:Adult; D000368:Aged; D004999:Amifostine / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects; D019610:Cytoprotection; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage* / Q000009:adverse effects; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis
chemical_list: D004999:Amifostine; D015255:Idarubicin