Malignancy-associated haemophagocytic lymphohistiocytosis

Haemophagocytic lymphohistiocytosis (HLH) is an inflammatory syndrome that can occur with cancer (malignancy-associated HLH) or with immune-activating therapies for cancer. Patients with lymphoma appear to be at particularly high risk for malignancy-associated HLH. The familial form of HLH is characterised by uncontrolled activation of macrophages and cytotoxic T cells, which can be identified by genetics or specific immune markers. However, the pathophysiology of malignancy-associated HLH is not well understood, and distinguishing pathological immune activation from the laboratory and clinical abnormalities seen in cancer and cancer treatment is challenging. Emerging diagnostic tools, such as serum cytokine or chemokine concentrations, flow cytometry, and other functional measures, are discussed. Mortality remains high with current approaches. Targeted therapy, including blockade of specific cytokines such as IL-1, IL-6, and IFNγ, and inhibition of the JAK-STAT pathways might improve outcomes for some patients. Finally, we discuss a framework for thinking of malignancy-associated HLH within a larger umbrella concept of cytokine storm syndrome.