title: Chromosomal abnormalities in Philadelphia chromosome negative metaphases appearing during imatinib mesylate therapy in patients with newly diagnosed chronic myeloid leukemia in chronic phase.
abstract: The development of chromosomal abnormalities (CAs) in the Philadelphia chromosome (Ph)-negative metaphases during imatinib (IM) therapy in patients with newly diagnosed chronic myecloid leukemia (CML) has been reported only anecdotally. We assessed the frequency and significance of this phenomenon among 258 patients with newly diagnosed CML in chronic phase receiving IM. After a median follow-up of 37 months, 21 (9%) patients developed 23 CAs in Ph-negative cells; excluding -Y, this incidence was 5%. Sixteen (70%) of all CAs were observed in 2 or more metaphases. The median time from start of IM to the appearance of CAs was 18 months. The most common CAs were -Y and + 8 in 9 and 3 patients, respectively. CAs were less frequent in young patients (P = .02) and those treated with high-dose IM (P = .03). In all but 3 patients, CAs were transient and disappeared after a median of 5 months. One patient developed acute myeloid leukemia (associated with - 7). At last follow-up, 3 patients died from transplantation-related complications, myocardial infarction, and progressive disease and 2 lost cytogenetic response. CAs occur in Ph-negative cells in a small percentage of patients with newly diagnosed CML treated with IM. In rare instances, these could reflect the emergence of a new malignant clone.
authors.affiliation: Department of Leukemia and, University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Lynne V
authors.initials: LV
authors.lastname: Abruzzo
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Jianqin
authors.initials: J
authors.lastname: Shan
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Rios
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D002869:Chromosome Aberrations / Q000187:drug effects*; D002986:Clinical Trials as Topic; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008677:Metaphase; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate