From the Guidelines
Hemophagocytic Lymphohistiocytosis (HLH) is a life-threatening condition requiring prompt diagnosis and treatment, with symptoms including persistent high fever, enlarged liver and spleen, cytopenia, high ferritin levels, and neurological abnormalities. The treatment of HLH typically begins with immediate immunosuppressive therapy using the HLH-94 or HLH-2004 protocol, which includes dexamethasone, etoposide, and cyclosporine 1. Some key points to consider in the treatment of HLH include:
- The use of pulsed corticosteroids and elements of HLH-94, with a clear indication for immediate administration of etoposide in severe HLH presenting with imminent organ failure 1
- The addition of IV immunoglobulin (IVIG) may be considered, due to its anti-inflammatory potential 1
- The use of anakinra may reduce mortality in sepsis patients with MAS features 1
- A personalized and graded treatment approach is advised, with early recognition and diagnosis of MAS-HLH being essential for efficacious management 1
- In adults, HLH-associated mortality remains high, especially in patients with underlying malignancies, and there is a need for novel agents 1
The disease results from immune dysregulation causing excessive activation of macrophages and T-cells, leading to a cytokine storm and multi-organ damage, as described in the study published in Haematologica in 2015 1.
Key Treatment Considerations
- Immunosuppressive therapy: using the HLH-94 or HLH-2004 protocol, which includes dexamethasone, etoposide, and cyclosporine 1
- Supportive care: including blood product transfusions, antimicrobial prophylaxis, and management of organ dysfunction
- Treatment of underlying infection: crucial in cases of infection-triggered HLH
- Allogeneic hematopoietic stem cell transplantation: often necessary for long-term survival in genetic or refractory HLH
Early recognition and aggressive treatment are essential as mortality rates are high without appropriate intervention, as highlighted in the study published in Blood in 2019 1.
From the Research
Symptoms of Hemophagocytic Lymphohistiocytosis (HLH)
- Fever and malaise are common non-specific symptoms of HLH, often shared with patients across a wide spectrum of conditions 2
- Hepatosplenomegaly, cytopenia, and hyperferritinemia are also characteristic of HLH 3, 4
- The initial symptoms of HLH are non-specific, but if left untreated, it can progress rapidly to multiorgan failure 3
- Significant liver function abnormalities can range from mild elevation of aminotransferases to fulminant hepatic failure with high mortality rates 5
Treatment Options for HLH
- Familial forms of HLH are currently treated with chemotherapy as a bridge to hematopoietic stem cell transplantation 4
- HLH occurring in rheumatic disease (macrophage activation syndrome) is treated with glucocorticoids, IL-1 blockade, or cyclosporine A 4
- In other forms of HLH, addressing the underlying trigger is essential 4
- Liver transplantation may be considered in some cases of HLH with severe liver dysfunction 5
- Early diagnosis and treatment are crucial for survival, and expert consultation is recommended to correctly interpret clinical, functional, and genetic findings and address therapeutic decisions 6