Cold agglutinin disease revisited: a multinational, observational study of 232 patients
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- 23 July 2020
- journal article
- research article
- Published by American Society of Hematology in Blood
- Vol. 136 (4), 480-488
- https://doi.org/10.1182/blood.2020005674
Abstract
We retrospectively studied 232 patients with cold agglutinin disease (CAD) at 24 centers in five countries. In Norway and a northern region of Italy, the study was close to being population-based. For the first time, we demonstrate 4-fold differences between cold and warmer climates regarding prevalence (20 versus 5 cases/million) and incidence (1.9 versus 0.48 cases/million/year). Mean baseline hemoglobin level was 9.3 g/dL, but 27% had hemoglobin < 8 g/dL. Identification of typical features of 'CAD-associated lymphoproliferative disorder' in the bone marrow was greatly increased by centralized biopsy assessment. CAD seems to be associated with a slightly increased risk of venous thrombosis. This work included a follow-up study of therapies, focusing on the long-term outcomes of the rituximab plus bendamustine and rituximab plus fludarabine regimens. Rituximab plus bendamustine therapy resulted in responses in 35 (78%) of 45 patients; 24 (53%) achieved complete response. Interestingly, these rates were still higher than observed in the original (2017) prospective trial, and we also found a shift towards deeper responses with time. This is explained by the prolonged time to response seen in many patients, probably related to long-lived plasma cells. In patients responding to rituximab-bendamustine, median response duration was not reached after 88 months, and estimated 5-year sustained remission was 77%. The regimen appeared safe regarding late-occurring malignancies. Rituximab plus fludarabine therapy seems to carry a higher risk of long-term adverse effects.Keywords
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