Therapy for chronic cold agglutinin disease: perspective for further improvements.

Abstract

Autoimmune haemolytic anaemia (AIHA) is a collective term for several disorders characterized by autoantibody-mediated destruction of erythrocytes1. AIHA are classified into warm-antibody and cold-antibody types, depending on the optimal temperature of action of the autoantibody. Primary chronic cold agglutinin disease (CAD) has been considered more difficult to treat than warm-antibody AIHA2. This is because of the lack of efficacy of therapy with corticosteroids or other non-specific immunosuppressive agents2,3. Unlike patients with warm AIHA, who often have general immune system dysregulation4,5, patients with CAD probably have competent regulation of the immune system, which explains the lack of association between CAD and other autoimmune disorders6. An increasing bulk of data has shown that primary CAD is a clonal, lymphoproliferative bone marrow disorder, which is most often non-progressive and clinically non-malignant3,7. It is not surprising, therefore, that non-specific immunosuppression or mild cytotoxic therapy usually fails to induce remission, while more specific and potent therapy directed at the pathogenic B-cell clone is more likely to succeed3. In this issue of Blood Transfusion, Gueli and colleagues describe a complete remission of more than 3 years’ duration following treatment with rituximab and bendamustine in combination in a heavily pre-treated patient with CAD not responding to previous chemotherapies8. The combination was well tolerated. If representative, this first published case observation may provide a clue to new treatment options in this challenging disease.