From the Guidelines
The treatment for Hemophagocytic Lymphohistiocytosis (HLH) involves aggressive immunosuppression to control the hyperinflammatory state, followed by addressing the underlying cause, with the most recent and highest quality study recommending the use of pulsed corticosteroids and elements of HLH-94, including dexamethasone 10 mg/m2 with or without a modified dose of etoposide 1.
Key Components of Treatment
- Initial therapy typically includes dexamethasone and etoposide, with the addition of cyclosporine in some cases
- The HLH-94 protocol, which includes dexamethasone, etoposide, and cyclosporine, aims to suppress the cytokine storm and control T-cell activation
- For refractory cases, additional agents like anakinra, ruxolitinib, or alemtuzumab may be used
- Supportive care is crucial, including management of cytopenias, infection prophylaxis, and neurological monitoring
Considerations for Specific Types of HLH
- For primary (genetic) HLH, allogeneic hematopoietic stem cell transplantation is ultimately necessary for cure, ideally performed once the disease is in remission
- For secondary HLH, treating the underlying trigger (infection, malignancy, or autoimmune disease) is essential alongside immunosuppression
- For EBV-HLH, the addition of rituximab to HLH-directed therapy may be effective in clearing the reservoir of virus, and monitoring of ferritin, sCD25, cell counts, and EBV DNA may guide treatment response 1
Importance of Prompt Treatment
- Untreated HLH has a high mortality rate due to progressive multi-organ failure from uncontrolled inflammation and macrophage activation
- Prompt treatment is critical to prevent irreversible organ damage and subsequent death
- The decision to start HLH-directed treatment depends on clinical judgment and assessment of organ function, with a clear indication for immediate administration of etoposide in severe HLH presenting with imminent organ failure 1
From the Research
Treatment for Hemophagocytic Lymphohistiocytosis (HLH)
The treatment for HLH varies depending on the underlying cause and the severity of the disease. Some key points to consider include:
- Familial forms of HLH are currently treated with chemotherapy as a bridge to hematopoietic stem cell transplantation 2
- HLH occurring in rheumatic disease (macrophage activation syndrome) is treated with glucocorticoids, IL-1 blockade, or cyclosporine A 2
- In other forms of HLH, addressing the underlying trigger is essential 2
- Immunosuppressive treatment protocols have been refined, and experience is gaining with alternative and salvage approaches 3
- Treatment with immune suppressants, etoposide, and allogeneic hematopoietic stem cell transplantation is also used 4
- Newer agents directed at subduing the uncontrolled immune response in a targeted fashion offer promise in this highly morbid disease 4
- Most centers use steroids and either etoposide-based (HLH-94/HLH-2004) or doxorubicin-based (CHOP) initial therapy regimens 5
Treatment Outcomes
The outcomes of treatment for HLH vary depending on the severity of the disease and the underlying cause. Some key points to consider include:
- More than 50% of children who undergo transplant survive, but adults have quite poor outcomes even with aggressive management 4
- Mortality in larger treatment-focused studies ranged from 20 to 88% 5
- Genetic HLH is always lethal if adequate therapy is not administered 6
- Severe acquired cases often lead to death without appropriate treatment 6
Future Research Directions
There is a need for more research on the treatment of HLH, particularly in adults. Some key areas for future research include: