Clinical Observation Of Dasatinib In The Treatment Of Chronic Myeloid Leukemia

[Objective]Chronic myeloid leukemia(CML)is a malignant clonal proliferative disease of the hematopoietic system,accounting for 15%of adult leukemia.The pathogenesis is formation of BCR-ABL fusion gene,whose product has an abnormal activation of tyrosine kinase activity,thus activating the downstream signal pathway,leading to proliferation out of control,differentiation blocked,inhibition of apoptosis.And thus inhibit the normal hematopoietic function,leading to infiltration and destruction of other organs.Imatinib is the first-line treatment on CML as the first generation of tyrosine kinase inhibitors,which achieved good therapeutic effect.But some patients can't benefit from imatinib because of primary,secondary resistance or intolerance to imatinib.The second generation TKI dasatinib has inhibitive effect on ABL/SRC pathways,benefiting patients of imatinib resistance or intolerant.Dasatinib was used as first-line treatment according to NCCN guidelines.This study was designed to observe the efficacy and safety of dasatinib in first-line and second-line treatment of patients with chronic myeloid leukemia.[Methods]We retrospectively analyzed five CML patients with dasatinib as first-line treatment and twenty-two cases resistant or intolerant to imatinib who switched to dasatinib from August 2012 to March 2017 in Qilu hospital,Shandong University.Four patients with dasatinib as first-line treatment were in chronic phase,while the other one was in blast crisis.Of twenty-two patients with dasatinib as second-line treatment,eighteen patients were in chronic phase,one patient was in acceleration period,three patients were in blast crisis.Of the twenty-two patients,mutations of BCR-ABL were detected in six patients.BCR-ABL changed from p210 to p230 in one patient.During the treatment,analysis of blood,chromosome and genetics examination were taken regularly to evaluate the efficacy.[Results]As of March 2017,the median duration of dasatinib therapy as first-line treatment was 25.5(11-36.67)months,and all five patients received complete hematologic response(CHR)and complete cytogenetic response(CCyR)and major molecular response(MMR).The median median time of the 22 patients treated with dasatinib was 9.25(3-51)months,including 18 in the chronic phase,1 in the accelerated phase and 3 in the blast crisis.Of the 18 patients with chronic phase,17(94.44%)received CHR,12(66.67%)received CCyR,7(38.89%)achieved MMR,and 3(16.67%)achieved MR4.5.One patient with accelerated phase did not receive CHR,CCyR,MMR or MR4 5.Only one case of CHR was found in 3 patients with blast crisis,and none of them had CCyR,MMR or MR4 5.Adverse reactions included headache,fluid retention and so on.[Conclusions]Dasatinib is effective in the treatment of some newly diagnosed and imatinib-resistant or intolerant patients.