Autoimmune hemolytic anemia (AIHA), Immune thrombocytopenia (ITP) and other autoimmune complications and extranodal involvement in CLL

[CLLerinOz]

"Autoimmune conditions are common in CLL and are often managed in a distinct manner from primary autoimmune disease. Leukemic involvement of other organs is rare in CLL and should be managed in a distinct manner from CLL without these manifestations. The following review summarizes the diagnosis and management of common autoimmune phenomenon related to CLL as well as an organ site specific approach to extranodal involvement in CLL."

This review article by Max J. Gordon and Alessandra Ferrajoli was published in the American Journal of Hematology on 01 May 2022. It's titled "Unusual complications in the management of chronic lymphocytic leukemia".

The article covers the following AUTOIMMUNE COMPLICATIONS:

Autoimmune hemolytic anemia (AIHA) - "Autoimmune hemolytic anemia (AIHA) occurs in approximately 5%–10% of patients with CLL and is most frequently of the IgG warm antibody (wAIHA) subtype, although IgM autoreactive antibodies targeting red blood cells and lead to cold agglutinin disease (CAD) can also be observed."

Immune thrombocytopenia (ITP) - "Immune thrombocytopenia (ITP) occurs in around 1%–5%" with CLL

"Co-occurring AIHA and ITP is called Evans syndrome and occurs in <1% of patients with CLL."

"Hypogammaglobulinemia is observed in ~25% of patients with CLL at diagnosis and subsequently develops in an additional 25% of patients throughout the course of their disease. Hypogammaglobulinemia contributes to the increased risk of infection in patients with CLL. Additionally, hypogammaglobulinemia can exacerbate autoimmune complications, particularly AIHA and ITP."

These rarer conditions are also discussed:

Pure red cell aplasia and autoimmune granulocytopenia - "pure red cell aplasia (PRCA) and autoimmune granulocytopenia (AIG) each occur in less than 1% of patients with CLL."

Acquired von Willebrand disease and acquired hemophilia A

Non-hematologic autoimmune conditions: Paraneoplastic pemphigus, Glomerulonephritis, Angioedema due to acquired C1 esterase inhibitor deficiency ("C1 esterase inhibitor deficiency has been reported in up to 4% of patients with CLL but is rarely symptomatic") and Myasthenia gravis (MG).

Figure 1 in the article provides a table titled "Treatment of autoimmune cytopenias in patients with CLL"

The article also covers EXTRANODAL INVOLVEMENT in the:

skin

central nervous system (CNS)

kidney

lung

heart and

gastrointestinal organ systems

The article concludes:

"The autoimmune phenomenon, especially AIC, complicates the management of the patient with CLL and contribute to the heterogeneous clinical course of the disease. AIHA and ITP are the most common manifestations and may occur at any point in the clinical course of the disease. In patients with CLL who meet IWCLL criteria for treatment and have AIC, CLL-directed therapies are utilized and are often effective in treating both CLL and AIC. In patients who do not meet treatment criteria for CLL, the optimal management of AIC consists of immunosuppression. Usually CLL has the typical leukemia phenotype but can, in rare cases, infiltrate any organ. Symptomatic extranodal involvement with CLL is an indication for treatment. Otherwise unexplained organ dysfunction in a patient with CLL should prompt evaluation of leukemic infiltration. Treatment in these instances should take into consideration sites of disease and the presence of organ function compromise."

onlinelibrary.wiley.com/doi...

Gordon, MJ, Ferrajoli, A. Unusual complications in the management of chronic lymphocytic leukemia. Am J Hematol. 2022; 97( S2): S26- S34. doi:10.1002/ajh.26585

This is an unlocked post so others can find it and our community. If you have questions specific to a particular condition described in this post, you may prefer to start your own, locked post on our site.

[CLLerinOz Administrator]

Figure 1 in the article presents a table titled "Treatment of autoimmune cytopenias in patients with CLL".

The article also contains the following summary of extranodal involvement in CLL.

Sites of extranodal involvement in CLL.

[CLLerinOz Administrator in reply to CLLerinOz]

This summary article, Strategies for Managing Autoimmune Complications in CLL, by Rose McNulty appeared in AJMC on Nov 13 2022.

ajmc.com/view/strategies-fo...

It reminds us that "While chronic lymphocytic leukemia (CLL) typically progresses slowly, awareness of rare but potentially serious complications is crucial to improve outcomes."

[CLLerinOz Administrator]

Key words here are 'rare' and 'awareness'. The article emphasises proper management of both the more common and the rare conditions which is a good thing. 😀

[LynnB1947]

CLLerinOZ - thanks for posting this article. Excellent information for rare complications to blood cancers. Nine years before I was diagnosed with SLL, I was diagnosed with membranous glomerulonephritis. At the time, I also had "B symptoms" - unexplained fevers & fatigue. I was treated with prednisone & cytoxan (cyclophosphamide), and the disease has been in remission since 2005. I was diagnosed with SLL in 2013 and treated with ibrutinib from 2014-2023. Currently on a drug holiday.

I suspected that my glomerulonephritis might be connected to my SLL. This article seems to confirm that.

Now I have a friend with follicular lymphoma (FL), and he appears to be suffering with AIHA and Paraneoplastic pemphigus. I sent this article to his wife as he has been hospitalized since July 3 with severe anemia, mouth sores, and blistering skin. I hope they will decide to go to a cancer hospital like MDA and perhaps get help from the author of this paper .... Dr. Alessandra Ferrajoli.

Thanks for sharing .... LynnB

[CLLerinOz Administrator in reply to LynnB1947]

Thanks for your reply, LynnB,

With fewer than 1% of those with CLL experiencing glomerulonephritis, you can count yourself unlucky that you were diagnosed with both conditions. Good to hear you've not been troubled by the glomerulonephritis for such a long time.

I hope your friend with FL gets the help he needs to control such difficult and uncomfortable symptoms.

CLLerinOz

[LynnB1947 in reply to CLLerinOz]

I'm hoping my friend with FL doesn't really have paraneoplastic pemphigus as that it appears to be very hard to treat. Perhaps his edema, blistering, bed sores, and mouth sores are caused by something that's less threatening.

[CLLerinOz Administrator in reply to LynnB1947]

I hope so, too. It sounds very difficult to be going through, whatever the cause.

CLLerinOz