Chromosomal abnormalities in Philadelphia chromosome-negative metaphases appearing during imatinib mesylate therapy in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase.
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.
Department of Leukemia, The University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Jorge
J
Medina
Hagop
H
Kantarjian
Moshe
M
Talpaz
Susan
S
O'Brien
Guillermo
G
Garcia-Manero
Francis
F
Giles
Mary Beth
MB
Rios
Kimberly
K
Hayes
Jorge
J
Cortes
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D002869:Chromosome Aberrations; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics*; D015466:Leukemia, Myeloid, Chronic-Phase / Q000235:genetics*; D008297:Male; D008677:Metaphase; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate