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Chromosomal abnormalities in Philadelphia chromosome-negative metaphases appearing during imatinib mesylate therapy in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase
Article first published online: 17 SEP 2003
Copyright © 2003 American Cancer Society
Volume 98, Issue 9, pages 1905–1911, 1 November 2003
How to Cite
Medina, J., Kantarjian, H., Talpaz, M., O'Brien, S., Garcia-Manero, G., Giles, F., Rios, M. B., Hayes, K. and Cortes, J. (2003), Chromosomal abnormalities in Philadelphia chromosome-negative metaphases appearing during imatinib mesylate therapy in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase. Cancer, 98: 1905–1911. doi: 10.1002/cncr.11729
- Issue published online: 22 OCT 2003
- Article first published online: 17 SEP 2003
- Manuscript Accepted: 25 JUL 2003
- Manuscript Revised: 15 MAY 2003
- Manuscript Received: 20 FEB 2003
- chronic myelogenous leukemia (CML);
- Philadelphia chromosome;
- clonal evolution
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.
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.
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.
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. Cancer 2003. © 2003 American Cancer Society.