Front-Line Treatment with Second-Generation Tyrosine Kinase Inhibitors Following By Allo-Transplantation Benefits Patients with Better Survival Inph-Positive Acute Lymphoblastic Leukemia

The treatment of Ph-positive acute lymphoblastic leukemia (Ph+ ALL) has entranced into tyrosine kinase inhibitors (TKIs) era. As the promising results in the treatment of chronic myeloid leukemia (CML), the second-generation TKI dasatinib has been placed as the frontline treatment of Ph+ ALL. However, who could benefit from the first line treatment of the second-generation TKIs is still unclear.Aim of this single center study is to compare the efficacy and safety of the first- and second-generation TKIs in the first-line treatment of Ph+ ALL. 77 newly diagnosed Ph+ ALL patients were enrolled and treated with TKIs combining with intensive chemotherapy, followed by allo-HSCT if donors were available. The BCR-ABL level in bone marrow was examined by RTQ-PCR and used as MRDmonitoring. 45 patients were treated with the first-generation TKI, and 32 with the second-generation TKIs. There was no significant difference in early response, including CRrate, major molecular response (MMR) and MRD negative rate between the two groups. With median follow-up of 456 (59-2327) days, a trend toward better DFS (P=0.088), but not OS (P=0.210), was seen in the patients treated with the second-generation TKIs. In subgroup analysis, both the DFS (P=0.050) and OS (P=0.048) were statistically higher in the second-generation TKIs group only if the patients received allo-HSCT.Both being treated with the second-generation TKIs and receiving allo-HSCT were multivariateanalyzedto be favorable factors for survival. There was much higher incidence of acquiring T315I mutation (4/8 vs. 1/9) after relapsed on the second-generation TKIs. In conclusion, front-line treatment of Ph+ ALL patients with the second-generation TKIs, especially dasatinib, is as effective and safe as imatinib; when allo-HSCT is incorporated as consolidation therapy following CR1, survival benefit was observed with second-generation TKIs. T315I occurred at much higher rates when patients relapsed on the second-generation TKIs and deserved further attention.