TY - JOUR
T1 - Chromosomal Abnormalities in Philadelphia Chromosome-Negative Metaphases Appearing during Imatinib Mesylate Therapy in Patients with Philadelphia Chromosome-Positive Chronic Myelogenous Leukemia in Chronic Phase
AU - Medina, Jorge
AU - Kantarjian, Hagop
AU - Talpaz, Moshe
AU - O'Brien, Susan
AU - Garcia-Manero, Guillermo
AU - Giles, Francis
AU - Rios, Mary Beth
AU - Hayes, Kimberly
AU - Cortes, Jorge
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2003/11/1
Y1 - 2003/11/1
N2 - BACKGROUND. Anecdotal cases of chromosomal abnormalities in Philadelphia chromosome (Ph)-negative metaphases have been reported in patients with chronic myelogenous leukemia (CML) in the chronic phase during treatment with interferon and, more recently, with imatinib. This phenomenon is different from true clonal evolution in that the additional cytogenetic abnormality occurs in Ph-negative cells. METHODS. The authors analyzed their experience with 342 patients with CML in chronic phase treated with imatinib to investigate the frequency and significance of this event. RESULTS. After a median follow-up of 30 months (range, 16-35 months), 21 patients (6%; 95% confidence interval, 0.04, 0.09) developed 25 chromosomal abnormalities in Ph-negative cells. Thirteen (54%) of these abnormalities were seen in 2 or more metaphases. The median time from the start of treatment with imatinib to the appearance of the abnormalities was 6 months (range, 3-22 months). The most common cytogenetic abnormality detected was trisomy 8 (33%). Twenty of 21 patients (95%) achieved a major (Ph < 35%) cytogenetic response (complete cytogenetic response in 13-62%). After a median follow-up of 22 months (range, 4-33 months), all 21 patients were alive, 20 of them in chronic phase and in complete hematologic response. None of the patients showed features of myelodysplasia. CONCLUSIONS. Cytogenetic abnormalities occur in Ph-negative cells in a fraction of patients with CML in chronic phase treated with imatinib. With a short follow-up, no clear clinical consequences can be identified.
AB - BACKGROUND. Anecdotal cases of chromosomal abnormalities in Philadelphia chromosome (Ph)-negative metaphases have been reported in patients with chronic myelogenous leukemia (CML) in the chronic phase during treatment with interferon and, more recently, with imatinib. This phenomenon is different from true clonal evolution in that the additional cytogenetic abnormality occurs in Ph-negative cells. METHODS. The authors analyzed their experience with 342 patients with CML in chronic phase treated with imatinib to investigate the frequency and significance of this event. RESULTS. After a median follow-up of 30 months (range, 16-35 months), 21 patients (6%; 95% confidence interval, 0.04, 0.09) developed 25 chromosomal abnormalities in Ph-negative cells. Thirteen (54%) of these abnormalities were seen in 2 or more metaphases. The median time from the start of treatment with imatinib to the appearance of the abnormalities was 6 months (range, 3-22 months). The most common cytogenetic abnormality detected was trisomy 8 (33%). Twenty of 21 patients (95%) achieved a major (Ph < 35%) cytogenetic response (complete cytogenetic response in 13-62%). After a median follow-up of 22 months (range, 4-33 months), all 21 patients were alive, 20 of them in chronic phase and in complete hematologic response. None of the patients showed features of myelodysplasia. CONCLUSIONS. Cytogenetic abnormalities occur in Ph-negative cells in a fraction of patients with CML in chronic phase treated with imatinib. With a short follow-up, no clear clinical consequences can be identified.
KW - Chronic myelogenous leukemia (CML)
KW - Clonal evolution
KW - Imatinib
KW - Philadelphia chromosome
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U2 - 10.1002/cncr.11729
DO - 10.1002/cncr.11729
M3 - Article
C2 - 14584073
AN - SCOPUS:0142243204
SN - 0008-543X
VL - 98
SP - 1905
EP - 1911
JO - Cancer
JF - Cancer
IS - 9
ER -