Figure 6.

Combined AVA4746 and chemotherapy treatment prolongs the survival of mice with primary relapsed B-lineage acute lymphoblastic leukemia. (A) NSG mice were intravenously injected with 50,000 LAX7R cells per mouse and then treated with either AVA4746 or the PBS vehicle control (15 mg/kg by oral gavage twice a day continuously for 14 days) 2 days after injection with LAX7R cells. In addition, 3 days after LAX7R cell injection, mice were treated with VDL alone (0.5 mg/kg vincristine once a week, 10.5 mg/kg dexamethasone five times a week and 1500 IU/kg L-asparaginase five times a week for 4 weeks) intraperitoneally or in combination with AVA4746 by oral gavage. (B) Kaplan-Meier survival analysis for the experimental design shown in (A). The MST was 38 days for both the PBS group (n=5) and the AVA4746 group (n=5). The 68-day MST of the VDL-treated group (n=6) was significantly different from the 78.5-day MST of the AVA4746- and VDL-treated group (n=6). ^*P=0.01. (C) The same protocol as that performed in (A) was conducted, except for that the dose of AVA4746 was higher (30 mg/kg) and the treatment time was longer (twice a day for 28 days). (D) Kaplan-Meier survival analysis for the experimental design shown in (C). The MST was 46.5 days for the PBS group (n=4), whilst the MST was 46 days for the AVA4746 group (n=5). The 77-day MST of the VDL-treated group (n=5) was significantly different compared with the 87-day MST in the group treated with the combination of both AVA4746 and VDL (n=5). ^*P=0.023. NSG, NOD.Cg-Prkdc^scidIl2rg^tm1Wjl/SzJ; MST, mean survival time; VDL, vincristine, dexamethasone and L- asparaginase; p.o., per os; i.p. intraperitoneal.