Cold Agglutinin Disease and Cancer

Cold agglutinin disease (CAD) is a disorder in which the immune system mistakenly attacks red blood cells (RBCs) in cold temperatures.

The cause of CAD is often not known, but the disease can sometimes manifest as a secondary autoimmune disorder in response to lymphoid malignancies and, less often, solid tumors.

How cancer can cause CAD

While the actual mechanism by which cancer leads to CAD is not fully known, scientists think that antibodies produced by the immune system against cancer proteins mistakenly bind to proteins that are normally found on the surface of red blood cells and activate their destruction.

Types of cancer associated with CAD

The most common malignancies associated with CAD are lymphomas or leukemias, both blood cancers that can be caused by the abnormal growth of a subset of immune cells called B-cells. B-cells are responsible for producing antibodies against foreign antigens to fight infections and malignancies.

Specific types of lymphoid malignancies that may be associated with CAD include Waldenström macroglobulinemia (WM), chronic lymphocytic leukemia (CLL), monoclonal gammopathy of undetermined significance (MGUS), and other types of non-Hodgkin’s B-cell lymphoma.

Cases of CAD associated with solid tumors are rare, although some have been described for cancers of the lung, colon, cervix, and breast.  CAD mostly appears when these cancers are advanced, meaning they have metastasized or spread.

Other details

In most cases, CAD that develops in the context of cancer is resolved by treating the cancer itself.


Last updated: Aug. 17, 2019


Cold Agglutinin Disease News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.