title: Factors predicting complete remission and subsequent disease-free survival after a second course of induction therapy in patients with acute myelogenous leukemia resistant to the first.
abstract: Patients with newly diagnosed acute myelogenous leukemia (AML) with persistent leukemia after their first course (CO1) of induction chemotherapy are generally given a second similar course, although their outcome is known to be worse than CO1 responders even when a complete remission (CR) is achieved. To identify specific patients who should or should not receive a second induction course identical to the first we analyzed outcome in 370 patients with persistent AML after CO1 who received a second identical course. One hundred and forty-two (38%) achieved CR on this course; median subsequent disease-free survival (DFS) in these 142 was 29 weeks and 10% were alive in CR at 5 years. The 5-year DFS of CO2 responders was significantly lower than that of CO1 responders (10 vs 24%, P < 0.001). Logistic regression identified pretreatment cytogenetic abnormalities (except inv 16, t(8;21), or t(15;17)), presence of an antecedent hematologic disorder or secondary AML as each having unfavorable prognostic import similar to the case in untreated patients. Treatment with "high-dose' rather than standard-dose cytarabine increased the probability of 2nd course CR. The occurrence of pneumonia, sepsis, or major hemorrhage were prognostically unfavorable, primarily in the high-dose cytarabine group, and, once in CR, DFS was shorter in this group. Equations predicting probability of 2nd course CR were derived. If validated prospectively these could be used to assign patients to either receive a second course of initial induction therapy or to change to salvage or investigational therapy after the first course. Alternatively, they could be used to stratify patients entering a prospective randomized trial comparing these two strategies.
authors.affiliation: Department of Hematology, University of Texas MD Anderson Cancer Center, Houston 77030, USA.
authors.forename: P
authors.initials: P
authors.lastname: Anderlini
authors.forename: H M
authors.initials: HM
authors.lastname: Ghaddar
authors.forename: T L
authors.initials: TL
authors.lastname: Smith
authors.forename: S
authors.initials: S
authors.lastname: Pierce
authors.forename: H M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: S
authors.initials: S
authors.lastname: O'Brien
authors.forename: M J
authors.initials: MJ
authors.lastname: Keating
authors.forename: E J
authors.initials: EJ
authors.lastname: Freireich
authors.forename: E H
authors.initials: EH
authors.lastname: Estey
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D016015:Logistic Models; D008875:Middle Aged; D011379:Prognosis; D012074:Remission Induction; D012307:Risk Factors
chemical_list: D003561:Cytarabine