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Journal Article
Review
How I manage patients with cold agglutinin disease.
British Journal of Haematology 2018 May
Cold agglutinin disease (CAD) is an uncommon autoimmune haemolytic anaemia in which a well-defined, clonal low-grade lymphoproliferative disorder of the bone marrow results in erythrocyte destruction mediated by the classical complement pathway. The pathogenesis, clinical features and diagnostic criteria are reviewed. Although anaemia is mild in some patients, approximately one-third of untreated patients have a haemoglobin level of ≤80 g/l, and about 50% have been considered transfusion dependent for shorter or longer periods. Therapy has improved greatly during the last 15 years. Mild disease can be managed by avoidance of cold and adequate precautions in specific situations, without drug therapy. Corticosteroids should not be used to treat CAD. Patients requiring pharmacological therapy should be considered for prospective trials. Outside clinical studies, the rituximab-bendamustine combination or rituximab monotherapy is recommended in the first line, depending on individual patient characteristics. Second-line options are rituximab-fludarabine in fit patients or, although less strongly documented, a bortezomib-based regimen. Therapies targeting the classical complement pathway are promising, and the complement C1s inhibitor, BIVV009, has shown favourable results in preliminary studies.
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