HLH Treatment Guidelines

General Principles

The American Society of Hematology recommends that HLH treatment be individualized according to subtype and underlying cause, with corticosteroids as first-line treatment for most cases and additional specific therapies based on clinical response and HLH type 1, 2
HLH is a severe hyperinflammatory syndrome that requires early recognition and treatment to prevent irreversible organ damage and death, with management adapted to HLH type, triggering cause, and clinical severity 3, 4

First-line treatment: high-dose corticosteroids, such as methylprednisolone 1g/day for 3-5 consecutive days, and simultaneous treatment of the underlying cause 1, 2
Second-line treatment: cyclosporine A (2-7 mg/kg/day) and anakinra (2-10 mg/kg/day SC) for inadequate response to corticosteroids 1, 2

MAS-HLH: first-line treatment with high-dose corticosteroids, and second-line treatment with cyclosporine A, anakinra, or tocilizumab 1, 2, 5
HLH associated with malignancy: treatment directed at the underlying malignancy, along with anti-HLH therapy, with better prognosis in HLH associated with B-cell lymphoma and Castleman disease 1, 2

Frequent clinical reassessment (at least every 12 hours) and monitoring of inflammatory parameters and organ function 1, 2, 5
Supportive care, including ventilation, vasopressors, renal replacement therapy, and transfusions, as needed 5

Factors associated with higher mortality: shock at ICU admission, platelet count <30 g/L, and HLH associated with malignancies 1, 5
Emerging therapies under investigation: ruxolitinib, emapalumab, and alemtuzumab 1, 5

Delayed diagnosis and treatment, which significantly increases mortality 5
Inadequate use of antimicrobials in cases where infection is the primary trigger, and direct application of pediatric protocols without adjustments for adults 3, 4, 5

For patients not responding to corticosteroids within 24-48 hours, the American Society of Hematology recommends adding etoposide (consider reduced dose of 50-100 mg/m² weekly in adults with comorbidities) 6
The European Hematology Association suggests considering rituximab (anti-CD20 antibody) for EBV-triggered HLH, as an addition to the treatment regimen 7
The American Society of Hematology advises that treatment must be tailored to the underlying condition and clinical severity, due to the heterogeneity of adult HLH 6
Consider allogeneic hematopoietic stem cell transplantation for primary HLH and in selected cases of refractory secondary HLH, as recommended by the American Society of Hematology 6

For malignancy-associated HLH, the European Hematology Association recommends treatment that targets both the HLH and the underlying malignancy; etoposide-containing regimens are particularly effective 7