Haemophagocytic lymphohistiocytosis post-alemtuzumab

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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.

Image from Wikipedia

The clinical features of HLH include:

  1. Fever
  2. Enlarged liver and/or spleen
  3. Skin rash
  4. Lymph node enlargement
  5. Breathing problems
  6. Easy bruising and/or abnormal bleeding
  7. Kidney abnormalities
  8. Heart problems
  9. 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.

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21 comments

  • Hmmm – does this fit with the B-cell driven autoimmunity hypothesis? The timing looks similar.

    This is a little concerning for someone like me who has already had multiple severe autoimmune problems post alemtuzumab. Rituximab has helped me thus far, but am really hoping to be on the other side of the risk period soon!

  • Maybe a solution to the problem could be to have certified hospitals to administer Lemtrada, those that can offer a timely and specialised response to any issues that might occur. Most of the issues that emerge seem managable with the right approach.

  • Will this and the other complications result in the monthly screening needing to be extended, both in duration and in what we are tested for?
    Agree with Anon about specialist hospitals – I’ve just been referred back to my local NHS from one of the London centres and am concerned as to the capacity to offer effective screening and response if I do have symptoms of any complications.

      • The chickens are coming home to roost, Don Giovannoni.

        It seems your “momentous year” proclamations in circa 2012, and my cautious rebuttals asking for you to be more intelligently circumspect, has finally come full circle, homeboy.

        What do you do now? Is Team G hanging its head in shame?

        Ten years of this increasingly outdated blog has delivered, ultimately, nowt.

        • “Ten years of this increasingly outdated blog ”

          Problem is MS got stuck with neurologists and all it’s untreatable diseases..Then the MRI came in and they all thought if we stop new lesions and relapses..we have cured it. No.

          MS needs hematologists
          and virologists to treat EBV.
          From Betaseron to Ocrevus
          worthless drugs that drained
          govt. coffers and hurt the public
          by stealing $ for healthcare.

          • That’s an interesting point – I hadn’t thought about it quite like that – just how much has the introduction of the MRI influenced MS research and focus upon the visible components of the pathology?

      • It really doesn’t’ make any sense to me:
        1) I want a clear indication who wrote what. It makes thing easier to search and it creates a sense of accountability and it makes us readers feel more connected, more in touch with you authors. You become a living, real person. If you’re using a “generic” name, to me, it just looks like you’re trying to hide who wrote what. (I recognize the irony of saying that and posting as an anonymous 😉 But it is not my blog after all and you owners/admins can easily reconnect my comments from logged IPs. I don’t want to remain anonymous to you, but I prefer to remain anonymous for the rest of the world)
        2) If you’re the only one posting as a BartsMSBlog, it even makes less sense, as from the name itself it seems that this is like an official BartsMSBlog consensus. We regular readers know that you guys don’t have the same opinion all the time – and that is a GOOD thing IMO. I LIKE hearing different perspectives on the same subject.

        BTW, I really admire your and your colleagues thick skin, as this blog attracts too many abusive, angry, bitter, jealous people. But that’s internet communication in general, it just brings out the worst in some people… I say f* them, as no-one is forcing them to be here and read/comment. I don’t always agree with you, but I more than appreciate reading about your opinions.

        • Their bitter because they have MS and pharma are dragging their heels to find a cure when treatment is much more profitable. DMD that damage immune system is not the answer. And When their being prompted to garner pharma accolades it pisses some off.

    • ProfG…..Apparently he was accused of Self Promotion..We’ve had the court case and the jury says who cares “Stay Calm and Carry On”

  • Thanks for sharing this. How many cases have their been of HLH post treatment with Lemtrada? Is it just these two?

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