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Cold agglutinin disease.

ABSTRACT: Primary chronic cold agglutinin disease (CAD) is a well-defined clinicopathologic entity in which a specific, clonal lymphoproliferative B-cell bone marrow disorder results in autoimmune hemolytic anemia. The immune hemolysis is entirely complement-dependent, predominantly mediated by activation of the classical pathway and phagocytosis of erythrocytes opsonized with complement protein C3b. Typical clinical features in CAD have diagnostic and therapeutic implications. Pharmacologic treatment should be offered to patients with symptom-producing anemia or disabling circulatory symptoms. CAD should not be treated with corticosteroids. Based on an individualized approach, rituximab monotherapy or rituximab-fludarabine in combination is recommended as first-line therapy. Rituximab-bendamustine is still an investigational therapy. Although complement-modulating agents are still to be considered experimental in CAD, therapy with the anti-C1s monoclonal antibody TNT009 seems promising.

SUBMITTER: Berentsen S

PROVIDER: S-EPMC6142439 | biostudies-other | 2016 Dec

REPOSITORIES: biostudies-other

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Cold agglutinin disease.

Berentsen Sigbjørn S

Hematology. American Society of Hematology. Education Program 20161201 1

Primary chronic cold agglutinin disease (CAD) is a well-defined clinicopathologic entity in which a specific, clonal lymphoproliferative B-cell bone marrow disorder results in autoimmune hemolytic anemia. The immune hemolysis is entirely complement-dependent, predominantly mediated by activation of the classical pathway and phagocytosis of erythrocytes opsonized with complement protein C3b. Typical clinical features in CAD have diagnostic and therapeutic implications. Pharmacologic treatment sho ...[more]

PMID: 27913484

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Cold agglutinin disease: current challenges and future prospects.

Project description:Cold agglutinin disease (CAD) is a complement-dependent, classical pathway-mediated immune hemolytic disease, accounting for 15-25% of autoimmune hemolytic anemia, and at the same time, a distinct clonal B-cell lymphoproliferative disorder of the bone marrow. The disease burden is often high, but not all patients require pharmacological treatment. Several therapies directed at the pathogenic B-cells are now available. Rituximab plus bendamustine or rituximab monotherapy should be considered first-line treatment, depending on individual patient characteristics. Novel treatment options that target the classical complement pathway are under development and appear very promising, and the C1s inhibitor sutimlimab is currently being investigated in two clinical Phase II and III trials. These achievements have raised new challenges and further prospects, which are discussed. Patients with CAD requiring therapy should be considered for clinical trials.

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Project description:Cold agglutinin disease (CAD) is a rare form of autoimmune hemolytic anemia with limited epidemiological and clinical data. We used the Danish National Patient Registries to examine CAD occurrence and risk of thromboembolic events (TEs) and mortality in CAD patients compared with a matched cohort from the general population in Denmark. We identified 72 patients diagnosed with CAD and 720 matched controls between 1999 and 2013. For 2013, the most recent year of study, crude incidence of CAD was 0.18 per 100 000 inhabitants per year and prevalence was 1.26 per 100 000 inhabitants. Risk of TEs was higher in the CAD patient cohort than in the comparison cohort at 1 year (7.2% of CAD patients had TEs vs 1.9% of comparisons), 3 years (9.0% vs 5.3%), and 5 years (11.5% vs 7.8%) after the index date. The median survival was 8.5 years. CAD patients had increased mortality compared with the general population cohort (adjusted hazard ratio [aHR], 1.84; 95% confidence interval [CI], 1.10-3.06; P = .020), with the highest mortality observed during the first 5 years after diagnosis (aHR, 2.27; 95% CI, 1.32-3.89; P = .003). Mortality rates 1 and 5 years after diagnosis were 17% and 39% in the CAD group vs 3% and 18% in the comparison cohort, respectively. CAD is a rare illness characterized by increased risk of TEs and mortality.

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