title: Chromosome abnormalities at onset of complete remission are associated with worse outcome in patients with acute myeloid leukemia and an abnormal karyotype at diagnosis: CALGB 8461 (Alliance).
abstract: Achievement of complete remission is essential for long-term survival of acute myeloid leukemia patients. We evaluated the prognostic significance of cytogenetics at complete remission in 258 adults with de novo acute myeloid leukemia and abnormal pre-treatment karyotypes, treated on Cancer and Leukemia Group B front-line studies, with cytogenetic data at onset of morphological complete remission. Thirty-two patients had abnormal karyotypes at time of initial complete remission. Of these, 28 had at least 1 abnormality identified pre-treatment, and 4 acute myeloid leukemia-related abnormalities not detected pre-treatment. Two hundred and twenty-six patients had normal remission karyotypes. Patients with abnormal remission karyotypes were older (P<0.001), had lower pre-treatment white blood counts (P=0.002) and blood blast percentages (P=0.004), were less often classified as Favorable and more often as Adverse among European LeukemiaNet Genetic Groups (P<0.001), and had shorter disease-free survival (median 0.6 vs. 0.9 years; P<0.001) and overall survival (median 1.2 vs. 2.2 years; P<0.001) than patients with normal remission karyotypes. Sixteen patients with normal remission karyotypes also harbored non-clonal abnormalities unrelated to pre-treatment karyotypes. They had shorter overall survival than 210 patients with only normal metaphases (P=0.04). Forty-eight patients with any clonal or non-clonal chromosome abnormality at complete remission had worse disease-free survival (median 0.6 vs. 1.0 years; P<0.001) and overall survival (median 1.2 vs. 2.5 years; P<0.001) than 210 patients with exclusively normal metaphases. In multivariable analyses, after adjustment for age, the presence of any remission abnormality was associated with shorter disease-free survival (P=0.03) and overall survival (P=0.01). We conclude that detection of any abnormality at complete remission is an adverse prognostic factor. (clinicaltrials.gov identifier: 00048958).
authors.affiliation: The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Niederwieser
authors.affiliation: The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.|Alliance for Clinical Trials in Oncology Statistics and Data Center, Mayo Clinic, Rochester, MN, USA.
authors.forename: Deedra
authors.initials: D
authors.lastname: Nicolet
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Carroll
authors.affiliation: Monter Cancer Center, Hofstra North Shore-Long Island Jewish School of Medicine, Lake Success, NY, USA.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Kolitz
authors.affiliation: Comprehensive Cancer Center, Wake Forest University, Winston-Salem, NC, USA.
authors.forename: Bayard L
authors.initials: BL
authors.lastname: Powell
authors.affiliation: The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.|Alliance for Clinical Trials in Oncology Statistics and Data Center, Mayo Clinic, Rochester, MN, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Kohlschmidt
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Stone
authors.affiliation: Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
authors.affiliation: The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA krzysztof.mrozek@osumc.edu clara.bloomfield@osumc.edu.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Mrózek
authors.affiliation: The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA krzysztof.mrozek@osumc.edu clara.bloomfield@osumc.edu.
authors.forename: Clara D
authors.initials: CD
authors.lastname: Bloomfield
mesh_terms: D059786:Abnormal Karyotype; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002869:Chromosome Aberrations; D060965:Clonal Evolution; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult