No significance of derivative chromosome 9 deletion on the clearance kinetics of BCR/ABL fusion transcripts, cytogenetic or molecular response, loss of response, or treatment failure to imatinib mesylate therapy for chronic myeloid leukemia.

摘要

BACKGROUND: Although deletion of the derivative chromosome 9 (der 9; del-der 9) carries a poor prognosis in patients with chronic myeloid leukemia (CML) who are treated with hydroxyurea or interferon, its significance in patients on imatinib mesylate (IM) therapy is debated. METHODS: In the current study, the authors used a locus-specific indicator breakpoint cluster region/receptor tyrosine kinase (BCR/ABL) probe to evaluate the significance of del-der 9 in 163 patients with CML who had fluorescence in situ hybridization (FISH) results available. Serial changes in BCR/ABL fusion transcript levels also were monitored by using messenger RNA (mRNA) quantitative polymerase chain reaction (PCR). RESULTS: Of 163 patients, 22 (13.5%) had del-der 9 before commencing IM therapy. No differences were noted in the time to hematologic response (P = .598), major cytogenetic response (CyR) (P = .281), complete CyR (P = .883), major molecular response (MoR) (P = .125), or complete MoR (P = .834). In addition, the times to loss of response (LOR) (P = .974), treatment failure (P = .455; including primary hematologic or cytogenetic resistance and LOR), transformation-free survival (P = .276), and dose escalation of IM (P = .816) did not differ significantly between patients with and without del-der 9. The results of serial BCR/ABL mRNA quantitative PCR revealed similar patterns of BCR/ABL fusion gene reduction between the 2 groups. CONCLUSIONS: The presence of del-der 9 in patients with CML did not influence 1) the response to IM therapy in terms of hematologic response, CyR, or MoR; 2) LOR; 3) treatment failure; 4) progression to accelerated phase/blast crisis; or 5) time to dose escalation of IM. Therefore, the authors concluded that the detection of del-der 9 does not have an impact on the current management of patients with CML who are receiving IM therapy.