Early management of hemophagocytic lymphohistiocytosis/macrophage activation syndrome: a systematic literature review

Objectives A systematic literature review was undertaken to summarise and analyse the available evidence on the initial hemophagocytic lymphohistiocytosis and macrophage activation syndrome (HLH/MAS) treatment according to the distinctive pathologic background and/or triggering factors. Methods An electronic search in the main medical databases (PubMed, EMBASE, and Cochrane Library) was conducted, in order to select the studies providing information related to the HLH/MAS therapy. To further maximise the evidence derived from this systematic review, we focused our attention on clinical studies that included and described >10 HLH/MAS cases. Results This literature search led to identify 18,020 articles. After the screening by title, removal of duplicated records, and full-text assessment of the relevant articles, the final search output consisted of 167 articles that provided enough information on the medical management of patients with HLH/MAS In total, 77 clinical studies (including >10 patients) describing the early treatment of HLH/MAS have been included in the present analysis. Conclusions Primary HLH is typically managed according to the HLH-94 or HLH-2004 protocols, with the main aim of bringing the patient to a hematopoietic stem cell transplant (HSCT). Secondary forms of HLH/MAS can arise in 3 main clinical contexts, namely rheumatic disorders, oncological diseases, and previously healthy patients developing specific and/or severe infections. Accordingly, different and variable therapeutic approaches have been applied to these 3 categories of secondary HLH/MAS. Despite the survival improvements achieved in the last decades in patients with HLH/MAS, there is a strong need for prospective and controlled studies focused on each specific group of HLH/MAS.