title: Philadelphia-negative clonal hematopoiesis following imatinib therapy in patients with chronic myeloid leukemia: a report of nine cases and analysis of predictive factors.
abstract: There are increasing reports of Philadelphia-negative (Ph-negative) clonal hematopoiesis developing among patients with chronic myeloid leukemia (CML) treated with imatinib mesylate (IM). To establish the incidence and significance of these chromosomal abnormalities, we analyzed data on 141 consecutive patients with CML treated with IM at the British Columbia Cancer Agency and Vancouver General Hospital from 1999 to 2004. The cumulative incidence of developing a Ph-negative clone three years from the start of IM was 8.7% at a median of 13.3 months. The Ph-negative clonal abnormalities included monosomy 7 and/or trisomy 8 (seven patients), monosomy for chromosomes X and 22 (one patient), and a (12;16) translocation (one patient). Two of the patients presented with the same chromosomal abnormality in both Ph-negative and Ph-positive cells. None of the Ph-negative clonal abnormalities was associated with myelodysplasia. In a multivariate analysis, an interval from diagnosis to initiation of IM of 1 year or less was associated with an increased risk of developing a Ph-negative clone (relative risk = 20.2; P = 0.025). There was no difference, however, in event-free survival between patients who did and did not develop Ph-negative clones. Therefore, while the development of Ph-negative clonal hematopoiesis in patients with CML treated with IM is uncommon, it appears to be more frequent than that previously seen with IFN, but it does not seem to confer a worse prognosis.
authors.affiliation: The Leukemia/BMT Program of British Columbia, the Division of Hematology, 950 West 10th Avenue, Room 3300, Vancouver, British Columbia V5Z 4E3, Canada.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Lin
authors.forename: Hélène
authors.initials: H
authors.lastname: Bruyère
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Horsman
authors.forename: Tapio
authors.initials: T
authors.lastname: Pantzar
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Barnett
authors.forename: Donna E
authors.initials: DE
authors.lastname: Hogge
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Nevill
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Nantel
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Sutherland
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Toze
authors.forename: John D
authors.initials: JD
authors.lastname: Shepherd
authors.forename: Julye C
authors.initials: JC
authors.lastname: Lavoie
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Song
authors.forename: Clayton A
authors.initials: CA
authors.lastname: Smith
authors.forename: Donna L
authors.initials: DL
authors.lastname: Forrest
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D005260:Female; D006410:Hematopoiesis; D006801:Humans; D000068877:Imatinib Mesylate; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics*; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D012307:Risk Factors
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate