From the Guidelines
The treatment of Hemophagocytic Lymphohistiocytosis (HLH) should primarily involve a combination of immunoglobulins, glucocorticosteroids, cyclosporin A, and etoposide (VP16), as outlined in the HLH-94 and HLH-2004 protocols, with the goal of promptly controlling the hyperinflammatory state and addressing any underlying triggers 1. The choice of treatment for HLH depends on the underlying cause, with primary and infection-associated secondary HLH typically managed with immunoglobulins, glucocorticosteroids, cyclosporin A, and etoposide (VP16) 1.
- Key components of the treatment regimen include:
- Glucocorticosteroids to reduce inflammation
- Cyclosporin A to suppress the immune system
- Etoposide (VP16) to control the proliferation of immune cells
- Immunoglobulins to modulate the immune response
- In cases of malignancy-associated HLH, the treatment approach is less clear, but may involve a combination of HLH-directed therapy and malignancy-directed therapy, with etoposide potentially playing a key role in treating both the HLH and the underlying neoplasm 1.
- Supportive care is also crucial, including transfusion support, antimicrobial prophylaxis, and management of organ dysfunction.
- For refractory cases, salvage therapies such as alemtuzumab or anti-interleukin-1 treatment may be considered, and allogeneic hematopoietic stem cell transplantation may be necessary for definitive treatment of primary or refractory secondary HLH 1.
From the Research
Treatment Options for Hemophagocytic Lymphohistiocytosis (HLH)
- The treatment of primary HLH has become standardized based on the HLH-2004 protocol using cyclosporine, etoposide, and dexamethasone with or without intrathecal methotrexate followed by hematopoietic stem cell transplantation 2.
- For secondary HLH, treatment is directed at control of the underlying condition, and if unsuccessful, cytotoxic agents such as those in HLH-2004, steroids, intravenous γ-globulin, or targeted immune therapy have been used 2.
- Immunotherapy targeting CD52 expressed on immune effector cells of HLH is a rational therapeutic approach in patients too ill for traditional cytotoxic chemotherapy, as seen in the successful use of alemtuzumab to treat HLH due to systemic lupus erythematosus 2.
- Anakinra, a recombinant interleukin-1 receptor antagonist, has been reported to treat macrophage activation syndrome (MAS) and rheumatic secondary HLH, and its use as a first-line agent for HLH is being investigated 3.
- Etoposide-based therapy is a standard of care for HLH, and early response markers such as improvement in soluble CD25 (sCD25) can predict survival after treatment 4.
- Salvage therapy for refractory HLH includes alternative therapeutic approaches, and there is a need for more effective therapies with improved understanding of the cellular and molecular mechanisms of HLH 5, 6.
Specific Treatment Approaches
- Alemtuzumab has been used to treat HLH due to systemic lupus erythematosus 2.
- Anakinra has been used to treat secondary HLH, particularly in patients with macrophage activation syndrome (MAS) or rheumatic secondary HLH 3.
- Etoposide and dexamethasone are commonly used in the treatment of HLH, and early response markers can predict survival after treatment 4.
- Hematopoietic stem cell transplantation is used in the treatment of familial forms of HLH 6.
- Glucocorticoids, IL-1 blockade, or cyclosporine A are used to treat HLH occurring in rheumatic disease (macrophage activation syndrome) 6.