Hemophagocytic lymphohistiocytosis (HLH) is an immune-mediated disorder characterized by hyperactivation of the immune system, leading to a cytokine storm responsible for organ failures. Consequently, patients with HLH often require intensive care management, where their short-term prognosis is compromised (1-month mortality: 30 to 40%).
Therapeutic management is urgent and consists in treating associated pathologies and employing immunomodulatory therapy. Currently, there are no clear and consistent recommendations for guiding immunomodulatory treatment in HLH due to the lack of high-level evidence studies. Experts recommend corticosteroid therapy for mild forms, whereas etoposide is proposed for severe cases, especially those with organ failures. However, in clinical practice, its use in patients with multi-organ failure is not systematic due to concerns about potential severe side effects and uncertainty regarding the contribution of severe sepsis to the clinical and biological presentation. Consequently, initiation of etoposide is sometimes delayed.
Our hypothesis is that early treatment of severe HLH associated with organ failure using etoposide could reduce organ failures associated with this syndrome. Therefore, we aim to compare two strategies for initiating etoposide in severe HLH in intensive care: an early strategy where etoposide is prescribed at the onset of HLH-related organ failure, and a delayed strategy where etoposide is prescribed only if there is unfavorable progression (or lack of improvement) after treating associated pathologies, associated with corticosteroid therapy.
Adult patient
Hscore ≥ 169
Diagnosis of HLH established by the multidisciplinary team caring for the patient(A 24/7 hotline will be available in case of diagnostic uncertainty: this will be the direct line to the on-call intensivist at Avicenne Hospital, who can contact the coordinating investigator as needed)
First episode of HLH
Moribund patient with refractory distributive shock: multi-organ failure requiring noradrenaline > 2.5 µg/kg/min and imminent risk of death.
Inability to administer etoposide within 12 hours.
Patient treated with etoposide prior to admission to the intensive care unit.
Hypersensitivity to etoposide or any of its excipients.