From the Guidelines
Treatment of Hemophagocytic Lymphohistiocytosis (HLH) requires prompt, aggressive therapy targeting both the hyperinflammation and any underlying triggers, with the standard first-line treatment following the HLH-94/2004 protocol, which includes dexamethasone, etoposide, and cyclosporine, as recommended by the most recent study 1.
Key Components of Treatment
- Dexamethasone (initially 10 mg/m² daily, tapered over 8 weeks) to reduce inflammation and immune response
- Etoposide (150 mg/m² twice weekly for 2 weeks, then weekly) to delete activated T cells and suppress inflammatory cytokine production
- Cyclosporine (3-5 mg/kg/day, targeting trough levels of 200-300 ng/mL) to inhibit T cell activation and proliferation
Considerations for Treatment
- For CNS involvement, intrathecal methotrexate may be added to the treatment protocol
- Treatment duration typically spans 8 weeks, with continuation therapy for those requiring stem cell transplantation
- Supportive care is crucial, including antimicrobial prophylaxis, IVIG for hypogammaglobulinemia, and transfusion support
- For secondary HLH, treating the underlying cause (infection, malignancy, autoimmune disease) is essential
Salvage Therapies
- Refractory cases may require salvage therapies like alemtuzumab (1 mg/kg/day for 4 days), ruxolitinib (5-10 mg twice daily), or anakinra (2-10 mg/kg/day)
- Allogeneic hematopoietic stem cell transplantation is the definitive treatment for primary HLH and refractory secondary cases, ideally performed during remission
Importance of Prompt Treatment
- HLH represents a life-threatening immune dysregulation where activated macrophages and lymphocytes cause tissue damage and multiorgan failure through excessive cytokine production
- Mortality approaches 50% without appropriate treatment, as reported in the study 1
- Prompt and aggressive treatment is necessary to improve outcomes and reduce mortality in patients with HLH, as supported by the study 1 and 1
From the Research
Treatment Overview
- The treatment of Hemophagocytic Lymphohistiocytosis (HLH) aims at suppressing hypercytokinemia and eliminating the activated and infected cells 2.
- Treatment modalities include immunosuppressive, immunomodulatory, and cytostatic drugs; T-cell antibodies; and anticytokine agents 2.
- In genetic HLH, hematopoietic stem cell transplantation (HSCT) is needed for the correction of the immune defect 2, 3.
Treatment Protocols
- The HLH-94 and HLH-2004 treatment protocols, developed by the Histiocyte Society Study Group for HLH, are frequently used in the treatment of HLH 3, 4.
- These protocols contain etoposide, dexamethasone, and cyclosporine A, which have strong activity against proliferation of cytotoxic T/NK-cells and macrophages, as well as inhibitory activity against the cytokine storm that induces and maintains HLH 4.
- The HLH-2004 study confirmed the efficacy of etoposide and dexamethasone in HLH treatment, with a 5-year probability of survival of 61% 3.
Adult Treatment
- Treatment of HLH in adults requires a more individualized approach, depending on the underlying trigger, disease severity and course, as well as genetic background 4.
- Interdisciplinary patient care with rheumatologists, gastroenterologists, neurologists, pediatricians, the transplant team, and pathologists is a prerequisite to successful treatment 4.
- The algorithm of HLH treatment in adults is based more on expert opinion than on extensive scientific evidence 4.
Key Considerations
- Early treatment and aggressive supportive care are critical for management of HLH 5.
- Prompt diagnosis and treatment are essential, as mortality remains high, especially in adults 6.
- There remains a pressing need for more sensitive, context-specific diagnostic tools and safer, more effective therapies 6.