CUREHLH · European initiative to improve knowledge, treatment and survival of haemophagocytic syndromes in children

Haemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening inherited immune disorder of early childhood characterised by an uncontrolled immune response. Three disease causing genes have been identified in about half of the patients. Diagnosis is difficult, pathophysiology poorly understood, and treatment unsatisfactory with about 40% of the children dying from treatment failure or toxicity. All European scientists active in research and treatment of HLH have joined in a consortium to enforce collaboration, combine the various expertises, and provide access to material and data. In vitro studies and several murine models for HLH and diseases predisposing to HLH, will be used to get more insight into the pathophysiology of the diverse genetic defects. Studies will address the role of triggers and antigen-presenting cells, the influence of cytokines in the initiation and propagation of the uncontrolled immune response, the interaction of immune effector cells and soluble factors, and the mechanism of cytotoxicity in lymphocytes and natural killer cells. Data about geno-phenotype will be combined to evaluate how known and unknown genetic defects reflect on the clinical course and immunophenotype of the patients. A diagnostic algorithm, incorporating knowledge from the known defects, will be developed and optimised in all countries to facilitate earlier and reliable diagnosis, and to separate patients with unknown defects or acquired HLH. The identification of risk factors for treatment failure and toxicity will be used to design improved treatment strategies. An experimental treatment will be tested in a murine model and will be the basis for a less toxic treatment in the future. Earlier diagnosis, better insight into the pathophysiology, and development of less toxic treatments are the steps towards a higher cure rate in HLH. In a rare disease as HLH, only combined efforts on an European-wide level will be able to achieve these goals.