[Efficacy comparison of sequential treatment with first-line administration of second-generation and first-generation tyrosine kinase inhibitors in patients with Ph⁺ acute lymphoblastic leukemia followed by allogeneic hematopoietic stem cell transplantation]

Objective: To investigate the efficacy of sequential treatment with first-line administration of second-generation tyrosine kinase inhibitors (TKI) and first-generation TKI (imatinib) in patients with Ph⁺ acute lymphoblastic leukemia (Ph⁺ ALL) followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Retrospective analysis of clinical features and prognosis of 76 newly diagnosed Ph ⁺ALL patients from June 2011 to December 2015 treated by allo-HSCT combined with first-line administration of second-generation or first-generation TKI was performed and the efficacy compared. Results: Of 76 Ph⁺ ALL patients, first-generation TKI was administered in 57 cases, second-generation TKI in 19 cases, including 10 cases of nilotinib and 9 cases of dasatinib. There was no significant difference in age, WBC counts, additional chromosomal abnormalities, time form diagnosis to transplantation, transplantation type, conditioning regimen or TKI initiation time between the two groups. Complete remission (CR) rates at the fourth week of induction therapy in first-generation TKI group and second-generation TKI group was 93.0% and 94.7% (P=1.000), respectively. Major molecular response (MMR, BCR-ABL/ABL reduce 3 log) rates meanwhile were 46.0% and 40.0% (χ²=0.169, P=0.681). Relapse rates before transplantation were 14.0% and 10.5% (P=1.000). MMR rates before transplantation were 54.4% and 68.2% (χ²=1.152, P=0.283). The 2-year overall survival (OS) rates of first-generation and second-generation TKI group were 62.0% and 94.7% (χ²=5.765, P=0.016), 2-year event-free survival (EFS) rates were 46.3% and 84.2% (χ²=5.644, P=0.018), respectively. Univariate analysis showed that second-generation TKI could improve OS (HR=0.126, 95%CI 0.017-0.939, P=0.043). Multiple factors analysis showed that second-generation TKI (HR=0.267, 95%CI 0.081-0.873, P=0.029) and MMR before transplantation (HR=0.496, 95%CI 0.254-0.968, P=0.040) were good independent prognostic factors of EFS. Conclusions: There was significant difference in the efficacy of second-generation TKI and first-generation TKI for Ph⁺ ALL patients treated by allo-HSCT. First-line administration of second-generation TKI showed better efficacy than that of first-generation TKI for Ph⁺ ALL patients.