Objective To investigate the potential application of targeting at vascular endothelial growh factor (VEGF) induced apoptosis in leukemic cell lines by combined use of Bevacizumab and chemotherapeutic drug. Methods Leukemic cells were treated with several drugs at different concentrations in culture. The effect of VEGF, Bevacizumab and co-treated with Ara-C on leukemic cells proliferation were evaluated by CCK-8 and apoptosis and cell cycle were detected by flow cytometry (FCM). Results VEGF could enhance the proliferation of leukemic cells and caused a dose-dependent manner on U937 cell. It also increased the percentage of cells in S phase, tested by, and Bevacizumab group was decreased. Apoptotic rate of cells treated with Bevacizumab or co-treated with Bevacizumab and Ara-C for 48 h were significantly higher when compared with control or Ara-C group, respectively (P<0.05), but the apoptotic rate of VEGF group or VEGF and Ara-C group was lower (P>0.05). There was no significant difference in apoptotic rate between control and combined use of VEGF, Bevacizumab and Ara-C group(P>0.05). Conclusion VEGF could enhance the proliferation of some leukemic cells, and may contribute to leukemic cells survival and a resultant resistance to chemotherapy-triggered cell death. The study also showed that leukemic cells growth was significantly inhibited by Bevacizumab through directly against VEGF, and the sensitivity of leukemic cells for chemotherapeutic drug was increased.

OBJECTIVETo investigate the efficacy and side effects of the consecutive chemotherapeutic protocol, Tongji-96, for adult patients with Philadelphia chromosome negative acute lymphoblastic leukemia (Ph-aALL).

METHODSA retrospective analysis was conducted on 95 cases of Ph-aALL patients treated between January 2004 and December 2012 with Tongji-96 regimen in Tongji hospital, Shanghai.

RESULTSAmong these 95 patients, the overall complete remission (CR) rate was 92.6%, 7-year overall survival (OS) and event-free survival (EFS) rates were (39.3±5.9)% and (31.5±5.3)%, respectively, with the median survival of 28 months. Based on multivariable COX proportional hazards regression model analysis, patients with the poor karyotype and failed to achieve CR after first course induction therapy had a higher risk of mortality compared to those who had good or normal cytogenetics and achieved CR after 1 course of induction treatment [the risk ratios (RR) were 3.380 (95% CI 1.530-7.463, P=0.003) and 3.005 (95% CI 1.522-5.933, P=0.002)，respectively]. By means of Kaplan-Meier analysis and Log-rank test，patients aged less than 60 years and successively achieved CR after first induction therapy had more favorable 7-year OS and EFS rates. Patients with normal karyotype and hyperdiploidy had significantly higher 2-year OS and EFS rates compared with those with complex karyotype, t(4;11) translocation and other karyotypes.

CONCLUSIONAge (60 years as the cut-off)，treatment courses for achieving CR and cytogenetics were predictive factors for the prognosis of Ph-aALL from this retrospective study. As a comprehensive and sequential therapy protocol, Tongji-96 regimen was proved to obtain long-term survival, reduce risks for relapse and improve outcomes for part Ph-aALL patients.

Adult ; Antineoplastic Combined Chemotherapy Protocols ; Chromosome Aberrations ; Disease-Free Survival ; Humans ; Kaplan-Meier Estimate ; Karyotyping ; Philadelphia Chromosome ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Recurrence ; Remission Induction ; Retrospective Studies ; Translocation, Genetic