Outcomes Of Tyrosine Kinase Inhibitors Combined With Chemotherapy And Allogeneic Hematopoietic Stem Cell Transplantation In Philadelphia Chromosome-positive Adult Acute Lymphoblastic Leukemia

Objective: To evaluate the outcomes of Tyrosine Kinase Inhibitors combined with chemotherapy and allogeneic hematopoietic stem cell transplantation in the treatment of Philadelphia chromosome-positive adult acute lymphoblastic leukemia(Ph+ALL),as well as the prognostic significance of Ph+ALL.Methods: A retrospective analysis of 112 newly diagnosed adult Ph+ALL patients from January 2010 to January 2017,all patients were treated with TKI combined with chemotherapy,when applicable,by a hematopoietic stem cell transplant.Patients with Ph+ALL were divided into TKI group(85 cases)and unused TKI group(27 cases)according to whether TKI was used in the first induction chemotherapy period.According to the different treatment regimen of the patients,the patients were divided into transplanted group(23 cases),regular use of TKI combined with chemotherapy group(57 cases),irregular use of TKI combined chemotherapy group(32 cases).Comparative analysis of complete remission(CR),Total survival time(OS),and disease-free survival time(DFS).All patients were followed up to January 15,2017.The median follow-up time was 16.69 months(1.54-59.33 months).Results:1.After the first induction therapy,the CR rate of TKI group was significantly higher than non-TKI group(91.8%,74.1% respectively,P=0.023);the rate of negativity of two groups were 44.4%and 11.1% respectively(P=0.010);the median OS were 18.00 months and 9.92 months respectively,the 4-year OS were 44.4% and 11.1%respectively(P=0.009)and the median DFS were 14.69 months and 8.44 months respectively,the 4-year DFS were 21.5% and 13.2% respectively(P=0.017).Indicating that those patients who took chemotherapy in combination with TKI in the first induction therapy can improve the CR rate,the rate of negativity and prolong the survival time significantly.2.In the maintenance treatment,the survival of the patients was divided into transplanted group,regular use of TKI combined with chemotherapy group,irregular use of TKI combined chemotherapy group.The median OS among three groups were37.68 months,25.86 months and 6.80 months,respectively.The OS of the irregular use of TKI combined chemotherapy group was significantly lower than that of the transplanted group(P<0.001)and regular use of TKI combined with chemotherapy group(P<0.001),the difference was statistically significant.No significant difference was found between the transplanted group and the regular use of TKI combined with chemotherapy group(P = 0.621)in median OS.The median DFS were 35.98 months,16.60 months and 6.57 months,respectively.The DFS of the irregular use of TKI combined chemotherapy group was significantly lower than that of the transplanted group(P<0.001)and regular use of TKI combined with chemotherapy group(P<0.001),the difference was statistically significant.No significant difference was found between the transplanted group and the regular use of TKI combined with chemotherapy group(P = 0.633)in median DFS.Indicating that the survival of the patients who took TKI irregularly the worst,and there was no significant difference between the transplanted group and the regular use of TKI combined with chemotherapy group.Conclusion: The use of TKI regularly and continuously in the treatment of adult Ph+ALL can improve the CR rate and prolong the survival time significantly.Our results indicate that chemotherapy combined with TKI is an effective treatment option for adult Ph+ALL.