title: Prognostic impact of acquisition of cytogenetic abnormalities during the course of chronic myelomonocytic leukemia.
abstract: Karyotypic abnormalities are detected in 20-40% of chronic myelomonocytic leukemia (CMML) patients at initial diagnosis and have been shown to correlate with patients' outcome. The significance of acquisition of cytogenetic abnormalities (ACA) during the course of CMML, however, is largely unknown. In a cohort of 314 CMML patients, karyotypic abnormalities were detected in 106 (34%) patients at the time of diagnosis; and ACA were detected in 80 (25%) patients after a median interval of 17 months (range, 2-117 months). The most frequently observed ACA were a complex karyotype, followed by +21, -7/del(7q), del(20q), i(17q), and -17/del(17p). ACA appeared to occur more frequently in patients with a normal or lower risk karyotype. Progression to AML was seen in 44 of 80 (55%) patients with ACA versus 67 of 234 (29%) patients without ACA (P < 0.0001). Presence of ACA predicted an inferior leukemia-free survival (LFS) by univariate (P = 0.0435) and multivariate analysis (HR = 1.892, P = 0.006). While acquisition of a complex karyotype was positively correlated with AML progression (P = 0.0086), del(20q) was associated with a stable disease (P = 0.0198). We conclude that ACA occur in ∼20-30% of CMML patients during the course of disease, and are significantly associated with AML progression and a shorter LFS. Karyotypic abnormalities, either present at diagnosis or acquired during the course of disease, have prognostic implication in CMML patients.
authors.affiliation: Department of Hematopathology, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030.
authors.forename: Guilin
authors.initials: G
authors.lastname: Tang
authors.affiliation: Department of Hematopathology, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030.
authors.forename: Bing
authors.initials: B
authors.lastname: Fu
authors.affiliation: Department of Hematopathology, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030.
authors.forename: Shimin
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Hematopathology, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030.
authors.forename: Xinyan
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Hematopathology, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030.
authors.forename: Zhenya
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Department of Hematopathology, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030.
authors.forename: Shaoying
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Hematopathology, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030.
authors.forename: Kausar
authors.initials: K
authors.lastname: Jabbar
authors.affiliation: Department of Hematopathology, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Khoury
authors.affiliation: Department of Hematopathology, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030.
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.affiliation: Department of Hematopathology, the University of Texas MD Anderson Cancer Center, Houston, Texas, 77030.
authors.forename: Sa A
authors.initials: SA
authors.lastname: Wang
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 / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015996:Survival Rate