Role of tyrosine kinase inhibitor in induction therapy for Philadelphia chromosome-positive acute lymphoblastic leukemia / 白血病·淋巴瘤

ABSTRACT

Objective To explore the feasibility of low-dose chemotherapy (LDCT) combined with tyrosine kinase inhibitor (TKI) (LDCT+TKI regimen) as the first-line induction regimen for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+-ALL).Methods The efficacies and adverse effects of various induction regimens in 61 newly diagnosed patients with Ph+ ALL were retrospectively analyzed.Results The complete remission (CR) rate of the first induction therapy was 73.8 ％ (45/61) for all 61 cases,and that of the second induction therapy was 86.7 ％ (13/15) for non-remission (NR) patients after the first induction.The total CR rate for two-course induction was 95.1％ (58/61).Treatment related mortality happened in one case (1.6 ％) after the first induction therapy.The response rates between conventional-dose chemotherapy (CDCT)±TKI group and LDCT±TKI group were not statistically different [without TKI,65.5 ％ (19/29) vs 60.0 ％(3/5),P =0.812;with TKI,90.5 ％ (19/21) vs 100.0 ％ (6/6),P =0.432].The response rate of LDCT+TKI group was not statistically different from that of CDCT alone group (P =0.089).The introduction of TKI to LDCT and CDCT could improve the response rate (CDCT+TKI group,P =0.041;LDCT+TKI group,P =0.087).The total response rate of the induction therapy with TKI was significantly higher than that without TKI [92.6 ％ (25/27) vs 64.7 ％ (22/34),P =0.01].The response rate of the TKI-based second induction therapy for non-CR cases after the first induction therapy without TKI was significantly higher than that after the first induction therapy with TKI [100.0 ％ (8/8) vs 33.3 ％ (1/3),P =0.011].There were no significant differences in the efficacies of the first induction therapy between various genetic subgroups (all P ＞ 0.05),and the introduction of TKI to the treatment of various genetic subgroups could improve the efficacies to a certain extent without statistical significance (all P ＞ 0.05).The incidences of treatment related infections and bleeding due to the first induction therapy in all patients were 50.8 ％ (31/61) and 4.9 ％ (3/61),respectively.Compared with LDCT±TKI group,the overall incidences of treatment related infections and bleeding in CDCT±TKI group were higher,but there were no statistical significances [infection,56.0 ％ (28/50) vs 27.3 ％ (3/11),P =0.084;bleeding,6.0 ％ (5/30) vs 0 (0/1 1),P =0.405].The incidence of treatment related infections in LDCT+TKI group was significantly lower than that in CDCT+TKI group [0 (0/6) vs 71.4 ％ (15/21),P =0.002] or that in CDCT alone group [0 (0/6) vs 44.8 ％ (13/29),P =0.039].The incidence of bleeding in LDCT+TKI group was not statistically different from that in CDCT+TKI group or that in CDCT alone group (all P ＞ 0.05).Conclusion LDCT+TKI regimen as the first-line induction regimen in Ph+-ALL is deserved to be investigated further.