Efficacy of Early Convert to Dasatinib in Chronic Myeloid Leukemia Patients Who Inresponse or Intolerance to Imatinib

Blackground:Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm hallmarked by the presence of fusion protein kinase derived from reciprocal translocation between chromosome 9 and 22, breakpoint cluster region (BCR)-Abelsonleukemia virus (ABL). Since the discovery of a tyrosine kinase inhibitor (TKI), CML has become a chronic illness if managed appropriately. The use of the first generation of TKI such as imatinib, benefit for most CML patients, but there are still a significant number of patients resistance to imatinib , need switched to second generation TKIs, such as dasatinib or nilotinib. however the efficiency and safety of CML patients who inresponse or intolerance to imatinib early convert to dasatinib should clinical studies.

Objective: To evaluate the efficiency and safety of CML patients who inresponse or intolerance to imatinib early convert to dasatinib.

Methods:We retrospectively analyzed 70 CML patients who inresponse or intolerance to imatinib in Southern Hospital from March 2014 to April 2016;real-time quantitative PCR method was used to detect BCR-ABL1 fusion gene Sanger sequencer.

Results: 37 CML patients BCR/ABL (IS)>10% treated by imatinib for 3 to 6 months,

had early conversion to dasatinib. Among them, 31 cases had low response to imatinib (sokal score was middle and high risk) and 6 cases intolerance to imatinib. 24 cases (64.9%) reached BCR/ABL (IS) < 10% after convert to dasatinib for 3 months, and 6 cases (40.5%) reached MMR after convert to dasatinib for 6 months.15 cases (40.5%) reached MMR in 12 months after conversion to dasatinib.33 patients (treated with imatinib for 3 to 6 months) did not undergo early transformation. Among them, 31 patients had poor response to imatinib and 2 patients intolerance to imatinib ,these patients continued imatinib or add imatinib dose to 600mg or 800mg qd. 13 patients (51%) did not reach the BCR/ABL (IS) < 10% for next 3 months, only 12 cases (36.3%) achieved MMR after 12 months follow-up, and 4 patients changed to dasatinib or nilatinib becase detected mutation during follow-up.The most common hematological adverse effects during dasatinib treatment were thrombocytopenia, neutropenia, anemia, and non-hematological adverse effects such as edema, pleural effusion, alopecia, gastrointestinal reactions and rare pulmonary hypertension. AEs can be alleviated by reducing or suspending dasatinib use.

Conclusion: The cml patients who inresponse or intolerance to imatinib early convert to dasatinib will gain an earlier and greater benefit, and adverse effects of dasatinib are controllable.

Key words:Chronic myeloid leukemia, Imatinib, Dasatinib, Early conversion