title: Prognostic significance of additional cytogenetic abnormalities in newly diagnosed patients with Philadelphia chromosome-positive chronic myelogenous leukemia treated with interferon-alpha: a Cancer and Leukemia Group B study.
abstract: Secondary cytogenetic abnormalities at diagnosis of Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) have been associated with an inferior outcome in reported series of largely chemotherapy-treated patients. To date, no study has specifically focused on the prognostic significance of secondary karyotypic abnormalities, detected at the time of diagnosis, in interferon (IFN)-alpha treated patients. We compared the outcome of 29 newly diagnosed Ph+ CML patients with additional abnormalities to that of 234 sole Ph+ patients, treated on CALGB protocols with IFN-alpha alone or together with IFN-gamma or low-dose cytarabine. Complete and partial cytogenetic responses were achieved in 20 and 19% of sole Ph+ patients, compared to 23 and 18%, respectively, of patients with additional abnormalities (P=1.00). None of 4 patients with 'high-risk' secondary abnormalities [+8, +Ph and i(17)(q10)], for whom follow-up cytogenetic samples were available, achieved a cytogenetic response. With a median follow-up of 11.3 years, the median overall survival (OS) was 6.0 years for sole Ph+ patients compared to 7.5 years for patients with additional abnormalities (P=0.70), with corresponding 8-year OS of 36 and 38%, respectively. On multivariable analysis, only age (P<0.001) and white blood cell count (P=0.02) were associated with outcome. We conclude that, with the possible exception of +8, +Ph and i(17)(q10), additional chromosomal abnormalities at diagnosis are not associated with inferior outcome in Ph+ CML patients treated with IFN-alpha-based therapy.
authors.affiliation: The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA. farag-1@medctr.osu.edu
authors.forename: Sherif S
authors.initials: SS
authors.lastname: Farag
authors.forename: Amy S
authors.initials: AS
authors.lastname: Ruppert
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Mrózek
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Carroll
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Pettenati
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Le Beau
authors.forename: Bercedis L
authors.initials: BL
authors.lastname: Peterson
authors.forename: Bayard L
authors.initials: BL
authors.lastname: Powell
authors.forename: Howard
authors.initials: H
authors.lastname: Ozer
authors.forename: Richard T
authors.initials: RT
authors.lastname: Silver
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
authors.forename: Clara D
authors.initials: CD
authors.lastname: Bloomfield
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000627:therapeutic use*; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D016898:Interferon-alpha; D007371:Interferon-gamma