Clinical Characteristics And Efficacy Analysis Of TKIs Combined With Chemotherapy In The Treatment Of Adult Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia

Objective:To explore the efficacy and prognostic factors of first and second-generation tyrosine kinase inhibitors combined with chemotherapy in the treatment of adult Philadelphia chromosome-positive acute lymphoblastic leukemia(Ph+ALL).Methods:Case data were retrospectively analyzed from January 2014 to January 2020 in the first affiliated hospital of nanchang university,including clinic data of 93 Ph+ALL patients of the patient’s clinical symptoms,including gender,age,blood routine during the initial diagnosis,proportion of blasts,bone marrow immune classification and genetic testing,etc,using MICM(morphology,immunology,cell heritage and molecular)diagnostic mode,refer to the WHO2016 version of the standard,and exclude patients with mixed phenotypes of acute leukemia and chronic myeloid leukemia.The SPSS 25.0 software was used for statistical analysis.The comparison of count data was performed by the chi-square test,the measurement data was in accordance with the normal distribution by the t test,and the non-normal distribution was performed by the rank sum test.Kaplan-Meier method was used to calculate overall survival time and progression-free survival time,and Log-rank test was used.Multivariate prognostic analysis was based on COX regression model.It is P<0.05 that was considered statistically significant.Result:1.Baseline data: The median age of 93 patients was 40(15-75)years old,of which 47 were males and 46 were females.There were 68 patients in the first-generation TKIs(imatinib)group and 25 patients in the second-generation TKIs(dasatinib)group.The two groups of patients were in gender,age,white blood cell count at first visit,hemoglobin concentration at first visit,platelet count at first visit There were no significant differences in blood uric acid at first diagnosis,ratio of blasts at first diagnosis,chromosome karyotype,expression of myeloid antigen,liver/spleen/lymph node enlargement,and fusion gene type.However,the lactate dehydrogenase of patients in the dasatinib group using the second-generation TKIs was significantly higher than that in the first-generation TKIs group,and the difference was statistically significant(P=0.036).2.Comparison of the treatment of the first-generation and second-generation TKIs groups: the total complete remission rate(CR)was 89.2%,the initial induced complete remission(CR)rates of the first and second-generation TKIs were 88.2%and 92.0%(P=0.617),and the difference was not statistically significant.Age,sex,hemoglobin concentration,platelet count,blood uric acid,lactate dehydrogenase,ratio of blasts,different chromosomal karyotypes and gene mutations had no significant effect on the CR rates of the two groups of patients,and the differences were not statistically significant.Among the first-generation TKIs,the CR rate of patients with high leukocytes in the initial induction chemotherapy was lower than that of non-high-white patients,and the difference was statistically significant(P=0.046).The white blood cells of patients with second-generation TKIs had no significant effect on their CR rate.There was no statistically significant difference in OS and PFS between the two groups in terms of gender,age,and white blood cell count.3.Analysis of prognosis and prognostic factors shows that the median overall survival(OS)of the first-generation and second-generation TKIs groups were: 18 months and 25 months(P=0.038),and the median progression free survival(PFS)were: 12.5 months and 18 months(P=0.026),the differences were statistically significant.Multivariate analysis suggested the use of the second-generation TKIs group(Dasatinib)(HR=2.073,95% CI 1.109-3.874,P=0.022)and induction chemotherapy to obtain CR during treatment(HR=3.259,95% CI 1.489-7.131,P=0.003)is an independent influencing factor for the good prognosis of OS;during treatment,CR obtained by induction chemotherapy(HR=4.245,95% CI 1.913-9.419,P=0.000)is an independent influencing factor for the good prognosis of PFS;during treatment recurrence(HR=0.381,95%CI 0.231-0.63,P=0.001)is an independent factor affecting the poor prognosis of OS,and recurrence during treatment(HR=0.262,95%CI 0.156-0.44,P=0.000)is PFS independent influencing factors of poor prognosis.In conclusion:1.The first induced remission rate was 89.2%,the first-generation and second-generation TKIs were 88.2% and 92.0%,respectively.Age,sex,ratio of blasts,and cytogenetic abnormalities had no significant effect on the CR rate.Among the first-generation TKIs,the CR rate of patients with high leukocytes in the initial induction chemotherapy was lower than that of non-high-white patients,and the difference was statistically significant(P=0.046).The white blood cells of patients with second-generation TKIs had no significant effect on their CR rate.2.The second-generation TKIs combined with chemotherapy for the treatment of Ph+ALL has better overall survival time than the first-generation TKIs combined with chemotherapy,but there is no obvious advantage in the progression free survival time.3.Obtaining CR after induction chemotherapy can make Ph+ALL patients get a good prognosis,and recurrence during treatment is an independent poor prognostic factor for patients.