A review article recently published in Cancers discusses treatment approaches to autoimmune hemolytic anemia (AIHA) associated with chronic lymphocytic leukemia (CLL). AIHA occurs in about 10% of patients with chronic CLL.

The treatment of these patients should be carefully pondered and individualized depending on the presence of clinical symptoms, Autore et al wrote.

In cases of cold agglutinin disease (CAD), a type of AIHA, the authors suggest the use of warming coils to transfuse blood. They wrote, “In emergency situations, although the role of blood transfusion is crucial, immunoglobulins (0.4 g/kg for 5 days or 1 g/kg for 2 days) could be used as a bridging treatment but immunosuppressive drugs could be added.”

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There are also cases, though rare, in which CAD patients might need repeated transfusions despite being treated with a high dose of corticosteroids and rituximab. In these cases, patients should be admitted to an intensive care unit.

A strategy to reduce transfusion support may include the administration of immunoglobulins and/or plasma exchange. Plasma exchange can decrease intravascular levels of the immunoglobulin M (IgM) monoclonal protein. It is a valuable option in cases of urgency or when other options are unavailable. Therefore, according to Autore et al, it is recommended to exchange the plasma volume with albumin daily or every other day, even in the absence of prospective studies.

On the other hand, it is not advisable to treat CAD with the therapeutic approaches used in warm AIHAs. These treatments were not proven to be effective in most cases. For instance, an effective response to corticosteroids usually requires high-dose regimens.

Hence, the current guidelines suggest the introduction of a CLL-directed therapy in refractory patients. For example, patients with severe CAD may benefit from chemoimmunotherapy with bendamustine-rituximab. However, if patients are unfit for this regimen, first-line treatment with rituximab as a single agent is recommended, as it showed good overall response rates.

Additional treatments, such as Bruton’s tyrosine kinase (BTK) inhibitors, might add value to the treatment of CAD in patients with CLL, but further studies are needed.


Autore F, Pasquale R, Innocenti I, Fresa A, Sora’ F, Laurenti L. Autoimmune hemolytic anemia in chronic lymphocytic leukemia: a comprehensive review. Cancers (Basel). 2021;13(22):5804. doi:10.3390/cancers13225804