Efficacy Evaluation Of Tyrosine Kinase Inhibitors Combined With Chemotherapy In The Treatment Of Ph Positive Adult Acute Lymphoblastic Leukemia

Objective To evaluate the efficacy of Tyrosine kinase inhibitors(TKI) in combination with chemotherapy in the treatment of Philadelphia chromosome positive adult acute lymphoblastic leukemia(Ph+ALL).Methods The clinical data of 89 cases of de novo adult patients with Ph+ALL from January 2009 to February 2015 were retrospectively analyzed.69 patients were treated with TKI combined with chemotherapy and 20 patients were treated with chemotherapy alone.The overall response rate(ORR), relapse rate, overall survival(OS) and disease-free survival(DFS) were analyzed.Results Among 69 patients with median age of 38 years old in combination group,43(62.3%)were males and 26(37.7%)were females,with 56(81.2%) patients using imatinib,11(15.9%) dasatinib and 2(2.9%) nilotinib.Out of 20 patients with median age of 42 years old in chemotherapy alone group,12(60.0%) were male and 8(40.0%) were female. 13 elderly patients(age≥55 years old) and 56 middle-and-younger-aged patients were in combination group.12 patients underwent allo-HSCT,of which 8 patients underwent allo-HSCT in the first complete remission and 4 patients received allo-HSCT in non-complete remission. There were 46 deaths in combination group and 20 deaths in chemotherapy alone group in the follow-up. The ORR of combination group was higher than that of chemotherapy alone group(93.8% vs. 45.0%,P=0.000).The cumulative relapse rate of combination group was lower than that of chemotherapy alone group(66.7% vs. 88.9%),although no significant difference was observed(P>0.05).The average duration of complete remission were 6.9 months and 5.8 months respectively.The median OS of combination group was significantly longer than that of chemotherapy alone group(12 months vs. 4.5 months, P=0.000).The cumulative 6-month OS were 85.5% and 30.0%,and 1-year OS were 42% and 10%,while 2-year OS were 17.5% and 0%(P=0.000),respectively.No significant difference was found between the two groups in median DFS(7 months vs. 3 months,P>0.05),and the cumulative 6-month DFS were 54.9% and 34.5%,1-year DFS were 34.5% and 11.6%,while 2-year DFS were 18.6% and 0% respectively.The median OS of transplantation group was longer than that of non-transplantation group(19 months vs. 9 months),although no significant difference was observed(P>0.05),and the cumulative 6-month OS were 100% and 7.8%,1-year OS were 81.8% and 46.9%,while 2-year OS were 46.7% and 17.1%,respectively.No significant difference was found between transplantation group and non-transplantation group in median DFS(8.5 months vs. 7 months,P>0.05),and the cumulative 6-month DFS were 88.9% and 50.8%,1-year DFS were 76.2% and 27.2%,while 2-year DFS were 14.5% and 0%,respectively.No significant difference was observed in median OS between elderly patients and middle-and-younger-aged patients(13 months vs. 12 months,P>0.05),and the cumulative 6-month OS were 84.6% and 84.6%,1-year OS were 52.7% and 52.7%,while 2-year OS were 30.4% and 19.0%,respectively.No significant difference was found in median DFS between elderly patients and middle-and-younger-aged patients(6 months vs. 7 months,P>0.05),and the cumulative 6-month DFS were 59.2% and 64.2%,1-year DFS were 32.3% and 30.5%,while 2-year OS were 0% and 17.5%(P>0.05),respectively.The median OS had no significant difference between patients using imatinib and 2nd TKIs(13 months vs. 12 months,P>0.05),and the cumulative 6-month OS were 78.8% and 100%,1-year OS were 48.3% and 69.2%,while 2-year OS were 18.0% and 30.0%,respectively.The median DFS of patients using 2nd TKIs was longer than that of patients using imatinib(10 months vs. 7 months),although no significant difference was found(P>0.05),and the cumulative 6-month DFS were 68.4% and 58.6%,1-year DFS was 31.3% and 31.3%,while 2-year DFS was 17.4% and 0% respectively.The major adverse events of combination group and chemotherapy alone group during treatment were hematologic toxicities, infection,hemorrhage,gastrointestnal symptoms,peripheral neuropathy and fatigue.The adverse events had no difference between the two groups.Conclusions TKI in combination with chemotherapy has significantly improved the response rate and survival in adults with Ph+ALL,and has not increased related adverse events.We should pay close attention on obtaining patients’ cooperation for regular treatment.