title: Report of 34 patients with clonal chromosomal abnormalities in Philadelphia-negative cells during imatinib treatment of Philadelphia-positive chronic myeloid leukemia.
abstract: Imatinib mesylate (Gleevec), an inhibitor of the BCR-ABL tyrosine kinase, was introduced recently into the therapy of chronic myeloid leukemia (CML). Several cases of emergence of clonal chromosomal abnormalities after therapy with imatinib have been reported, but their incidence, etiology and prognosis remain to be clarified. We report here a large series of 34 CML patients treated with imatinib who developed Philadelphia (Ph)-negative clones. Among 1001 patients with Ph-positive CML treated with imatinib, 34 (3.4%) developed clonal chromosomal abnormalities in Ph-negative cells. Three patients were treated with imatinib up-front. The most common cytogenetic abnormalities were trisomy 8 and monosomy 7 in twelve and seven patients, respectively. In 15 patients, fluorescent in situ hybridization with specific probes was performed in materials archived before the initiation of imatinib. The Ph-negative clone was related to previous therapy in three patients, and represented a minor pre-existing clone that expanded after the eradication of Ph-positive cells with imatinib in two others. However, in 11 patients, the new clonal chromosomal abnormalities were not detected and imatinib may have had a direct effect. No myelodysplasia was found in our cohort. With a median follow-up of 24 months, one patient showed CML acceleration and two relapsed.
authors.affiliation: Cytogenetic and Clinical Departments, Hôpital André Mignot, Versailles, France. cterre@ch-versailles.fr
authors.forename: C
authors.initials: C
authors.lastname: Terre
authors.forename: V
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authors.lastname: Eclache
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authors.lastname: Rousselot
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authors.lastname: Imbert
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authors.lastname: Charrin
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authors.lastname: Gervais
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authors.lastname: Mozziconacci
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authors.lastname: Maarek
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authors.lastname: Mossafa
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authors.lastname: Auger
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authors.lastname: Dastugue
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authors.lastname: Talmant
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authors.initials: J
authors.lastname: Van den Akker
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authors.initials: C
authors.lastname: Leonard
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authors.lastname: N'Guyen Khac
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authors.initials: F
authors.lastname: Mugneret
authors.forename: F
authors.initials: F
authors.lastname: Viguié
authors.forename: M
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authors.lastname: Lafage-Pochitaloff
authors.forename: J N
authors.initials: JN
authors.lastname: Bastie
authors.forename: G L
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authors.lastname: Roux
authors.forename: F
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authors.lastname: Nicolini
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authors.lastname: Maloisel
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authors.lastname: Vey
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authors.lastname: Laurent
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authors.lastname: Recher
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authors.lastname: Vigier
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authors.initials: Y
authors.lastname: Yacouben
authors.forename: S
authors.initials: S
authors.lastname: Giraudier
authors.forename: J P
authors.initials: JP
authors.lastname: Vernant
authors.forename: B
authors.initials: B
authors.lastname: Salles
authors.forename: J
authors.initials: J
authors.lastname: Roussi
authors.forename: S
authors.initials: S
authors.lastname: Castaigne
authors.forename: V
authors.initials: V
authors.lastname: Leymarie
authors.forename: G
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authors.lastname: Flandrin
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authors.initials: M
authors.lastname: Lessard
mesh_terms: D000328:Adult; D000368:Aged; D000782:Aneuploidy; D001549:Benzamides; D002869:Chromosome Aberrations; D002897:Chromosomes, Human, Pair 7; D002898:Chromosomes, Human, Pair 8; D002999:Clone Cells / Q000473:pathology; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015994:Incidence; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D011379:Prognosis; D011743:Pyrimidines / Q000627:therapeutic use*; D012189:Retrospective Studies
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate