Primary chronic cold agglutinin disease (CAD) is a clonal lymphoproliferative disorder accounting for 13-15% of autoimmune haemolytic anaemias. Significant advances have been made in treatment, which was largely unsuccessful until recently. The essential clinical, immunological and pathological features are reviewed, focusing on their relevance for therapy. Non-pharmacological management still seems sufficient in some patients. With the recent improvements, however, drug therapy seems indicated more often than previously thought. Corticosteroids should not be used to treat CAD. Half of the patients respond to rituximab monotherapy; median response duration is 11 months. Fludarabine-rituximab combination therapy is very effective, resulting in 75% response rate, complete remissions in about 20%, and more than 66 months estimated response duration. Toxicity is a concern, and benefits should be carefully weighed against risks. An individualized approach is discussed regarding the choice of fludarabine-rituximab combination versus rituximab monotherapy. Patients requiring treatment should be considered for prospective trials.
© 2011 Blackwell Publishing Ltd.