title: Acquisition of cytogenetic abnormalities in patients with IPSS defined lower-risk myelodysplastic syndrome is associated with poor prognosis and transformation to acute myelogenous leukemia.
abstract: We hypothesized that the dynamic acquisition of cytogenetic abnormalities (ACA) during the follow up of myelodysplastic syndromes (MDS) could be associated with poor prognosis. We conducted a retrospective analysis of 365 patients with IPSS low or intermediate-1 risk MDS who had at least two consecutive cytogenetic analyses during the follow up. Acquisition of cytogenetic abnormalities was detected in 107 patients (29%). The most frequent alteration involved chromosome 7 in 21% of ACA cases. Median transformation-free and overall survival for patients with and without ACA were 13 vs. 52 months (P = 0.01) and 17 vs. 62 months (P = 0.01), respectively. By fitting ACA as a time-dependent covariate, multivariate Cox regression analysis showed that patients with ACA had increased risk of transformation (HR = 1.40; P = 0.03) or death (HR = 1.45; P = 0.02). Notably, female patients with therapy-related MDS (t-MDS) had an increased risk of developing ACA (OR = 5.26; P < 0.0001), although subgroup analysis showed that prognostic impact of ACA was not evident in t-MDS. In conclusion, ACA occurs in close to one third of patients with IPSS defined lower risk MDS, more common among patients with t-MDS, but has a significant prognostic impact on de novo MDS.
authors.affiliation: Department of Leukemia, the University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Koichi
authors.initials: K
authors.lastname: Takahashi
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wang
authors.forename: A Megan
authors.initials: AM
authors.lastname: Cornelison
authors.forename: Lynne
authors.initials: L
authors.lastname: Abruzzo
authors.forename: Tapan
authors.initials: T
authors.lastname: Kadia
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.forename: Zeev
authors.initials: Z
authors.lastname: Estrov
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Mar
authors.initials: M
authors.lastname: Mallo
authors.forename: William
authors.initials: W
authors.lastname: Wierda
authors.forename: Sherry
authors.initials: S
authors.lastname: Pierce
authors.forename: Yue
authors.initials: Y
authors.lastname: Wei
authors.forename: Francisco
authors.initials: F
authors.lastname: Sole
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002869:Chromosome Aberrations; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D012307:Risk Factors; D012737:Sex Factors; D015996:Survival Rate; D013997:Time Factors