After yesterday’s post on alemtuzumab-related posts, many people are asking about haemophagocytic lymphohistiocytosis (HLH), which has been included as a complication of alemtuzumab treatment as is now in the SmPC (summary of product characteristics).
HLH is a condition in which the body makes too many activated macrophages and lymphocytes. People with HLH usually develop systemic symptoms, which may include fever, enlarged liver or spleen, cytopenias (decreased number of blood cells), and neurological abnormalities. HLH may either be inherited or acquired. The acquired causes of HLH include infection, medications that suppress the immune system, autoimmune diseases, immunodeficiencies, certain types of cancer and/or metabolic diseases. Interestingly, HLH can rarely result from an inappropriate immune response to the Epstein-Barr virus or another viral illness.
The clinical features of HLH include:
- Enlarged liver and/or spleen
- Skin rash
- Lymph node enlargement
- Breathing problems
- Easy bruising and/or abnormal bleeding
- Kidney abnormalities
- Heart problems
- Increased risk for certain cancers (leukaemia, lymphoma)
Many people with this condition also develop neurologic abnormalities. The neurological symptoms vary but may include irritability, fatigue, abnormal muscle tone, seizures, neck stiffness, mental status changes, ataxia, blindness, paralysis, and/or coma.
In acquired HLH, it is often necessary to treat the underlying condition. Antibiotics or antiviral medications are used to treat or prevent infections that may have triggered the exaggerated immune response. People with HLH are usually treated with chemotherapy and/or immunotherapy to destroy excess immune cells which can lead to life-threatening inflammation.
Case 1: The first post-alemtuzumab case reported below was treated with intravenous corticosteroids and a molecular adsorbent recirculation system procedure, presumably to remove autoantibodies. Unfortunately, she died one month after the first hospital admission due to liver failure.
Case 2: In comparison, the second post-alemtuzumab case responded to oral corticosteroid treatment combined with 2 doses of rituximab. He did well and has remained in remission from an HLH perspective.
Although emapalumab (Gamifant), an anti-interferon-gamma antibody, is licensed as a treatment for refractory HLH, we are not aware of it being tried in the post-alemtuzumab setting and whether the pathogenesis of the condition post-alemtuzumab is similar to that of the congenital or acquired HLH in children.
Saarela et al. Hemophagocytic lymphohistiocytosis in 2 patients with multiple sclerosis treated with alemtuzumab. Neurology. 2018 May 1;90(18):849-851.