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Clonal evolution in a patient with CML detected by FISH precedes imatinib treatment failure

Background

Imatinib (IM) inhibits the TK protein from chromosome Philadelphia (Ph). However, less than 10% of IM-treated patients become resistant. Second generation TK inhibitors are on active clinical research aimed to overcome most, but not all, important mutations.

Case report

A 61 year-old male was diagnosed on Sep/98 with CML chronic phase, he was treated with hydroxiurea, interferon and Ara-C. On July/01 the patient was on complete hematological response (CHR), but Ph positive in karyotyping (Ky) and fluorescence in-situ hybridization (FISH), there were not additional abnormalities. Patient began IM treatment, 400 mg/day. After 4 months of treatment, +der(22) was detected, but the patient was still on CHR. On subsequent visits, the patient had an increased frequency of chromosomal abnormalities, and after 2 years he lost CHR, regardless of the increase IM dose and the concomitant use of Ara-C. The patient was included on a dasatinib phase II protocol. 2 weeks after he had a profound cytopenia and 2 months after had CHR. Table 1 shows clinical and hematological and Ky and FISH follow-up.

Table 1 Clinical and hematological and Ky and FISH follow-up

Conclusion

Additional abnormalities found on Ky and FISH could preceed treatment failure. Molecular monitoring is required to guide treatment decisions. The role of second generation TK inhibitors needs to be defined.

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Correspondence to Eduardo Cervera.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Enriquez, V., Cruz, J., Gutierrez, O. et al. Clonal evolution in a patient with CML detected by FISH precedes imatinib treatment failure. BMC Cancer 7 (Suppl 1), A41 (2007). https://doi.org/10.1186/1471-2407-7-S1-A41

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  • DOI: https://doi.org/10.1186/1471-2407-7-S1-A41

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