title: Philadelphia chromosome mosaicism at diagnosis in chronic myeloid leukemia: clinical correlates and effect on imatinib mesylate treatment outcome.
abstract: In chemotherapy-treated patients with chronic myeloid leukemia (CML), the karyotypic detection of Philadelphia chromosome (Ph)-negative metaphases at diagnosis (i.e. Ph mosaicism) is not considered significant as a prognostic factor for survival. In the current retrospective study, clinical correlates and prognostic relevance of Ph mosaicism were evaluated in 63 Ph-positive patients with CML, including 59 in chronic phase and 4 in accelerated phase, receiving imatinib mesylate as either first (n = 46) or second (n = 17) line therapy. Thirteen patients (21%) displayed Ph-negative metaphases at diagnosis and, compared to the other 50 patients with 100% Ph-positive metaphases, presented with significantly lower leukocyte count (p = 0.0004), circulating blast percentage (p = 0.02), and incidence of palpable splenomegaly (p = 0.02). Ph mosaicism did not correlate with other CML-pertinent prognostic factors including Sokal score (p = 0.4) or the presence of additional chromosome changes (p = 0.96) found in 10 patients (16%). Neither Ph mosaicism nor the presence of additional chromosome changes affected complete or partial cytogenetic remission rates to IM. Multivariable analysis identified Ph mosaicism as a risk factor for shortened survival. Due to the small sample size, the current preliminary observations require validation in a larger group of patients.
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Landstrom
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Knudson
authors.forename: Gordon W
authors.initials: GW
authors.lastname: Dewald
authors.forename: Rhett P
authors.initials: RP
authors.lastname: Ketterling
authors.forename: Ayalew
authors.initials: A
authors.lastname: Tefferi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D002869:Chromosome Aberrations; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009030:Mosaicism / Q000187:drug effects; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000627:therapeutic use*; D011379:Prognosis; D011743:Pyrimidines / Q000627:therapeutic use*; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate