Assessment Of HLH-94and HLH-04Immunochemotherapy Protocol For Hemophagocytic Lymphohistiocytosis In Children: A Systematic Review And Meta Analysis

Objective Hemophagocytic lymphohistiocytosis (HLH) is a raregrave disease characterized by uncontrolled hyperinflammation on the basisof various inherited or acquired immune deficiencies. The survival for HLHpatients has improved dramatically since the HLH-94protocol has beenwidely accepted. Based on the cumulative experiences from HLH-94treatment study and other studies, a new protocol HLH-04had beendeveloped. The major difference of HLH-04protocol from HLH-94protocol was add cyclosporine A at the beginning of induction treatmentperiod. Accordingly the evaluation of these two trials was needed, since therisks and benefits of adding cyclosporine A in induction therapy were notyet defined, and there was still no research to compare these two protocols.Moreover, the small number of HLH patients made the comparison oftreatment outcomes for large randomized controlled trial of single-centerHLH patients very difficult. Therefore the present study was designed byapplying systmatic review and meta analysis method, to make a primarystudy on the therapy outcome differences between HLH-94and HLH-04protocol in children HLH patients, and to provide a meaningful evidence for pediatricians.Methods Searching the following database: PubMed, Web of SCI,Chinese Scientific Journals Fulltext Database (VIP) and China NationalKnowledge Infrastructure (CNKI) and the deadline time is2013.4.30.Meta-analysis were carried out by using the Stata12.0software.Results Our initial search criteria identified843articles from fourdatabase and2additional articles were identified through references fromthe identified articles. All the articles are case serial report studies. Weincluded3studies which contained the two therapy reports in themeta-analysis. When comparing the complete remission rate of inductiontherapy between groups treated with HLH-94and HLH-04protocols,statistical significance could be found, the OR is0.16,95%CI (0.04～0.57),p=0.005. It suggests that the complete remission rate of the HLH-04groupis higher than the HLH-94group one. When comparing the mortalitybetween HLH-94and HLH-04groups, there was no statistical significancebeen found, the OR is2.69，95%CI (0.12～61.01), p=0.535.Conclusion Both HLH-94and HLH-04protocols had improved thesurvival of HLH patients dramatically. With little published data on thetreatment information of HLH， our research suggests the completeremission rate of the HLH-04group is higher than the HLH-94group one,nonetheless it failed to present convincing evidence to suggest thatHLH-04protocol was more effective than HLH-94protocol in childrenHLH patients.