title: Risk stratification of chromosomal abnormalities in chronic myelogenous leukemia in the era of tyrosine kinase inhibitor therapy.
abstract: Clonal cytogenetic evolution with additional chromosomal abnormalities (ACAs) in chronic myelogenous leukemia (CML) is generally associated with decreased response to tyrosine kinase inhibitor (TKI) therapy and adverse survival. Although ACAs are considered as a sign of disease progression and have been used as one of the criteria for accelerated phase, the differential prognostic impact of individual ACAs in CML is unknown, and a classification system to reflect such prognostic impact is lacking. In this study, we aimed to address these questions using a large cohort of CML patients treated in the era of TKIs. We focused on cases with single chromosomal changes at the time of ACA emergence and stratified the 6 most common ACAs into 2 groups: group 1 with a relatively good prognosis including trisomy 8, -Y, and an extra copy of Philadelphia chromosome; and group 2 with a relatively poor prognosis including i(17)(q10), -7/del7q, and 3q26.2 rearrangements. Patients in group 1 showed much better treatment response and survival than patients in group 2. When compared with cases with no ACAs, ACAs in group 2 conferred a worse survival irrelevant to the emergence phase and time. In contrast, ACAs in group 1 had no adverse impact on survival when they emerged from chronic phase or at the time of CML diagnosis. The concurrent presence of 2 or more ACAs conferred an inferior survival and can be categorized into the poor prognostic group.
authors.affiliation: Department of Hematopathology and.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX; and.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Cortes
authors.affiliation: Department of Hematopathology and.
authors.forename: Guilin
authors.initials: G
authors.lastname: Tang
authors.affiliation: Department of Hematopathology and.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Khoury
authors.affiliation: Department of Hematopathology and.
authors.forename: Sa
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Hematopathology and.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Bueso-Ramos
authors.affiliation: Department of Pathology, Hartford Hospital, Hartford, CT.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: DiGiuseppe
authors.affiliation: Department of Hematopathology and.
authors.forename: Zi
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX; and.
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.affiliation: Department of Hematopathology and.
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.affiliation: Department of Hematopathology and.
authors.forename: Shimin
authors.initials: S
authors.lastname: Hu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D018570:Risk Assessment; D015996:Survival Rate
chemical_list: D047428:Protein Kinase Inhibitors