| Chronic lymphocytic leukemia (CLL) is a heterogeneous group of tumors. Some patients may have minimal or no symptoms for many years with a normal life expectancy, without requiring treatment. Others are symptomatic at diagnosis or early thereafter and can experience infectious and autoimmune complications, leading to a reduced lifespan. Over the past decades, more treatment strategies for CLL have been developed, especially monoclonal antibodies. Different combinations containing monoantibody come out but their efficacies are unclear. In this network-meta analysis we focused on efficacy of therapies for previously untreated chronic lymphocytic leukemia, especially examining the role of monoclonal antibodies in CLL treatment. We searched the following three databases (from2000to May3rd2013):Pubmed, EMBASE and Cochrane library. We used the terms "lymphoma" and similar or "chronic lymphocytic leukemia" and similar. We combined the search terms with the highly sensitive search strategy for identifying reports of RCTs in the Cochrane Handbook for Systematic Reviews of Interventions (version5.1.0).11publications were eligible in this meta-analysis. They were divided into five treatment groups (Table1). Seven trials (N=1885) evaluated traditional chemotherapy versus F&FC. Among them two studies did not report data on progression-free survival and both are abstracts. Two trials (N=1001) assessed the efficiency of FCR compared with F&FC and PCR relatively. Two trials (N=465) evaluated A&FCA compared with traditional chemotherapy and FCR relatively. Outcomes assessed were:3year progression-free survival (3Y-PFS), complete response (CR) and overall response (ORR). Our search yielded eleven trials including3,351cases. Main results include (1) ORR:FCR, A&FCA are statistically beneficent compared with traditional chemotherapy (2) CR: FCR is evaluated to bring statistically significant improvement compared with traditional chemotherapy (3) PFS:we don’t find significant differences among the five treatment groups (4) Rank:the most possible rankings are consistent referred to CR and ORR. Best to worst:FCR, A&FCA, PCR, F&FC, traditional chemotherapy. No PFS data is reported in PCR therapy. Its descending sequence concerned with PFS is:FCR, A&FCA, F&FC, traditional chemotherapy. Conclusion:Firstly, consistent with randomized controlled trails, addition of monoclonal antibodies ameliorates the survival outcomes especially CR and ORR. However, benefit on3Y-PFS is not significant. Secondly, in naive CLL patients rituximab segments hold a tendency to be more effective and less toxic than alemtuzumab-based ones. More well-designed trials are needed for evaluation.The Hedgehog signaling pathway regulates crucial steps during early embryonic development and tumorgenesis. But its status in chronic lymphocytic leukemia is contentious. We found a great heterogeneity for the expression levels of the hedgehog family with a subset of about25%samples showing high transcript levels (1.5-fold than the median). We confirmed a higher tendency of hedgehog expression in trisomy12subgroup. GANT61, a small molecule inhibitor of GLI, shows its time-and concentration-efficiency and the IC50value is13.27uM (11.57-15.22uM,95%CI,48hours). Furthermore our results indicated its delicious method works through BCL2and BAX. In addition, we found the hedgehog pathway may act through inhibition of STAT3phosphorylation. In conclusion, our results confirm the hedgehog pathway is a potential target in trisomy12subgroup and reveal its possible mechanism through STAT3activation for the first time. We demonstrate the inhibition of GANT61in chronic lymphocytic leukemia and argue for its further clinical development. Obviously, far more details are waiting to be deciphered in the network involving hedgehog and STAT3pathways. |
PDF Full Text Request