Upfront treatment with the first and second-generation tyrosine kinase inhibitors in Ph-positive acute lymphoblastic leukemia
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Guopan Yu1,*, Fang Chen1,*, Changxin Yin1, Qifa Liu1, Jing Sun1, Li Xuan1, Zhiping Fan1, Qiang Wang1, Xiaoli Liu1, Qianli Jiang1 and Dan Xu1
1Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China
*These authors have contributed equally to this work
Dan Xu, email: [email protected]
Keywords: tyrosine kinase inhibitor; BCR/ABL; acute lymphoblastic leukemia; efficacy; safety
Received: May 18, 2017 Accepted: September 08, 2017 Published: October 31, 2017
The treatment of Ph-positive acute lymphoblastic leukemia (Ph+ ALL) has entranced tyrosine kinase inhibitors (TKIs) era. Currently both imatinib and dasatinib are registered as the front-line treatment for Ph+ ALL, and the other 2nd-generation TKIs are suggested as an alternative for those who failed the first-line treatment. However, it remains unclear who could benefit from the 2nd-generation TKIs as the first-line treatment for Ph+ ALL. In this study we compared the efficacy and safety of the 1st and 2nd-generation TKIs in the front-line treatment of Ph+ ALL and found a trend toward better disease-free survival (DFS) in the 2nd-generation TKIs group, though no significant difference in early response and long-term survival between the two groups. Furthermore, subgroup analysis showed that if allogeneic hematopoietic stem cell transplantation (allo-HSCT) was incorporated as consolidation, the 2nd-generation TKIs benefited patients with better DFS and overall survival (OS). The two generation TKIs were well tolerated. Higher incidence of acquiring T315I mutation was observed in the patients relapsed on the 2nd-generation TKIs. These findings suggested front-line treatment of Ph+ ALL with the 2nd-generation TKIs might benefit patients with better survival when allo-HSCT was incorporated as consolidation therapy; meanwhile, the higher incidence of T315I mutation in patients relapsed on the 2nd-generation TKIs deserved further attention.
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