Haemophagocytic lymphohistiocytosis: a life threatening complication of lymphoma

Haemophagocytic lymphohistiocytosis (HLH), a hyperinflammatory syndrome leading to organ damage and death, may arise as a complication of lymphomas (L-HLH). L-HLH diagnosis is challenging and optimal treatment strategies, influenced by factors such as timing of onset, lymphoma subtype and disease severity, remain ill-defined. This narrative review summarises recent evidence to support clinicians in navigating the competing priorities posed by L-HLH, including the urgent need to control inflammation, establish a diagnosis and initiate lymphoma-directed therapy, while minimising toxicity and avoiding unnecessary immunosuppression.

While HLH-94 and H-score diagnostic criteria were not specifically designed for L-HLH, the optimised HLH inflammatory index (OHI) was developed in L-HLH patients and predicts the risk of multiorgan failure (MOF) but also benefit from etoposide. Recent evidence also highlights improved survival with early administration of lymphoma targeting drugs while, in critically unwell patients, non-myelosuppressive treatment with anakinra, ruxolitinib and intravenous immunoglobulins (IVIg) might offer a survival advantage. Finally, novel markers such as C-X-C motif chemokine ligand 9 (CXCL-9), recently shown to identify patients responding to interferon γ blockade, might become more widely available in the future.

L-HLH encompasses a wide range of clinical presentations that force clinicians to balance competing priorities. Recent evidence improves patients stratification and supports early administration of lymphoma targeting drugs when feasible, etoposide in high risk patients and non-myelosuppressive regimens in critically unwell patients.