title: Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461).
abstract: We analyzed prospectively 1213 adults with de novo acute myeloid leukemia (AML) to ascertain the prognostic impact of cytogenetic abnormalities on complete remission (CR) rate, 5-year cumulative incidence of relapse (CIR), and 5-year overall survival (OS). All patients received similar induction therapy. Median follow-up for surviving patients was 8.3 years. Nonprioritized cytogenetics distinguished t(8;21) and inv(16)/t(16;16) as conferring a significantly better prognosis than normal karyotype. Prognostic impact of many abnormalities could not be determined independently because of their association with complex karyotype. Neither complex karyotype nor secondary aberrations affected outcome of patients with t(8;21), inv(16)/t(16;16), or t(9;11). Among other patients, those with complex karyotypes had significantly worse outcomes than cytogenetically normal patients. Based on outcome for specific cytogenetic abnormalities and karyotype complexity, patients were divided into 3 risk groups: favorable (CR 88%, CIR 54%, OS 55%), intermediate (CR 67%, CIR 67%, OS 24%), and adverse (CR 32%, CIR 92%, OS 5%). Multivariate analyses confirmed the major contribution of cytogenetics to the probability of attaining CR, CIR, and OS. For the adverse-risk group, the probability of achieving CR was 4.0 and 11.9 times lower, the probability of relapse 3.0 and 4.4 times higher, and the risk of death 2.1 and 4.3 times higher than those for the intermediate and favorable groups, respectively. We conclude that although the prognostic impact of many recurring abnormalities has not been ascertained independently of complex karyotype, cytogenetics is among the most useful factors predicting attainment of CR, CIR, and long-term survival in adult AML.
authors.affiliation: Division of Hematology and Oncology, Comprehensive Cancer Center, The Ohio State University, Columbus 43210-1240, USA. byrd-3@medctr.osu.edu
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Mrózek
authors.forename: Richard K
authors.initials: RK
authors.lastname: Dodge
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Carroll
authors.forename: Colin G
authors.initials: CG
authors.lastname: Edwards
authors.forename: Diane C
authors.initials: DC
authors.lastname: Arthur
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Pettenati
authors.forename: Shivanand R
authors.initials: SR
authors.lastname: Patil
authors.forename: Kathleen W
authors.initials: KW
authors.lastname: Rao
authors.forename: Michael S
authors.initials: MS
authors.lastname: Watson
authors.forename: Prasad R K
authors.initials: PR
authors.lastname: Koduru
authors.forename: Joseph O
authors.initials: JO
authors.lastname: Moore
authors.forename: Richard M
authors.initials: RM
authors.lastname: Stone
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Mayer
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Feldman
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Davey
authors.forename: Charles A
authors.initials: CA
authors.lastname: Schiffer
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
authors.forename: Clara D
authors.initials: CD
authors.lastname: Bloomfield
mesh_terms: D000208:Acute Disease; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D002869:Chromosome Aberrations; D007446:Chromosome Inversion; D002877:Chromosomes, Human / Q000648:ultrastructure; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D015993:Life Tables; D011446:Prospective Studies; D012008:Recurrence; D012074:Remission Induction; D012307:Risk Factors; D016019:Survival Analysis; D014178:Translocation, Genetic; D016896:Treatment Outcome; D014314:Trisomy
chemical_list: D003561:Cytarabine; D003630:Daunorubicin