Peripheral blood monitoring of chronic myeloid leukemia during treatment with imatinib, second-line agents, and beyond.

ABSTRACT

BACKGROUND: The current study was conducted to compare simultaneously obtained bone marrow (BM) cytogenetics (CTG), peripheral blood (PB) and BM fluorescence in situ hybridization (FISH), and quantitative real-time polymerase chain reaction (Q-PCR) for BCR-ABL1 in monitoring response to treatment with tyrosine kinase inhibitors and homoharringtonine (HHT) in patients with chronic myeloid leukemia (CML). METHODS: PB and BM FISH (n = 112 samples) and/or Q-PCR (n = 132 samples) for BCR-ABL1 were simultaneously obtained in 70 patients with Philadelphia chromosome-positive (Ph+) CML in chronic (68%), accelerated (16%), and blast phase (16%) before the initiation of therapy and during the course of treatment with imatinib (IM) (n = 40 patients), dasatinib (n = 20 patients), nilotinib (n = 4 patients), bosutinib (n = 18 patients), or HHT (n = 4 patients) for patients with newly diagnosed (n = 13 patients), IM-sensitive (n = 34 patients), IM-resistant (n = 30 patients), or IM-intolerant (n = 9 patients) disease. Eighteen patients were found to have Ph+ variants or karyotypic abnormalities in addition to the Ph+. RESULTS: Excellent correlations (r) were observed between PB and BM FISH (r = 0.95) and PB and BM Q-PCR (r = 0.87), as well as BM CTG and PB FISH (r = 0.89) and PB Q-PCR (r = 0.82). This correlation was not affected by the presence of the Ph+ variant or additional chromosomal abnormalities, the presence of ABL1 kinase domain mutations, phase of the disease, or treatment. CONCLUSIONS: PB FISH and Q-PCR appear to be reliable methods with which to monitor response to modern therapy in patients with all phases of CML.