Monitoring chronic myeloid leukemia (CML) response to tyrosine kinase inhibitors (TKI) and homoharringtonine (HHT) using peripheral blood (PB) fluorescence in situ hybridization (FISH) and quantitative RT-PCR (Q-PCR): Are bone marrow biopsies still needed?

Abstract

7064 Background: The purpose of this study is to compare simultaneously obtained PB and bone marrow (BM) BCR-ABL FISH and Q-PCR to monitor response to TKI and HHT in CML. Methods: Between January 2005 and December 2008, 52 patients (pts) with chronic (n = 37, 80%), accelerated (n = 6, 7%), and blast phase (n = 9, 14%) CML had 112 simultaneous PB and BM FISH and Q-PCR before and/or after start of imatinib (IM, n = 27), dasatinib (n = 9), nilotinib (n = 1), bosutinib (n = 13), or HHT (n = 2) for newly diagnosed (n = 27), IM resistant (n = 20), or IM intolerant (n = 5) CML. 13 (26%) had chromosomal abnormalities in addition to the Philadelphia chromosome, and 10 (20%) had a detectable BCR-ABL mutation including the T315I in 2 pts. Results: 24 (46%) had simultaneous PB and BM FISH and/or Q-PCR measurements obtained at 1 time point, 9 (17%) at 2; 9 (17%) at 3; 10 (20%) at > 4 time points before and/or post-initiation of TKI or HHT. Excellent concordance was observed between PB and BM at all time points for both FISH (r = 0.96; p = 0.0003) and Q-PCR (r = 0.88; p= 0.0015). Correlation was not affected by the presence of additional chromosomal abnormalities, phase of the disease, treatment (TKI or HHT), or the number of prior therapies. Conclusions: FISH and Q-PCR are reliable methods to monitor CML response to TKI and HHT in patients with CML and may render the need for BM biopsy monitoring obsolete. No significant financial relationships to disclose.