Exclusive Occurrence of <i>k</i> Chains in Isolated Cold Haemagglutinins

Harboe, Morten; Furth, R. Van; Schubothe, H.; Lind, K.; Evans, Robert S.

doi:10.1111/j.1600-0609.1965.tb01303.x

Cited by 95 publications

(24 citation statements)

References 22 publications

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“…Considering the lack of effect of corticosteroids and conventional immunosuppressive agents, 1,6,9 it may be hypothesized that mechanisms related to unspecific immune suppression are not essential. Previous studies of rituximab therapy were based on the presence of a clonal lymphoproliferative B-cell disorder in the bone marrow of most if not all patients with primary CAD, 2,4,9,24 testing the hypothesis that targeting the pathogenic cell clone would provide an efficient therapy. 11,12 We previously found, however, that PR was often achieved even though the median IgM level reduction was modest (only 54%).…”

Section: Discussionmentioning

confidence: 99%

“…The epidemiology, pathogenetic mechanisms and clinical features of chronic cold agglutinin disease (CAD) have been quite extensively elucidated in the literature, [1][2][3][4][5] but therapy remains suboptimal. [6][7][8][9][10] Although most authors emphasize the importance of avoiding cold exposure, a population based study showed that drug therapy had been attempted in more than 70% of the patients, 9 indicating that counseling is insufficient as sole therapeutic measure in a majority.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

High response rate and durable remissions following fludarabine and rituximab combination therapy for chronic cold agglutinin disease

Berentsen

Randen

Vågan

et al. 2010

Blood

148

109

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IntroductionThe epidemiology, pathogenetic mechanisms and clinical features of chronic cold agglutinin disease (CAD) have been quite extensively elucidated in the literature, 1-5 but therapy remains suboptimal. [6][7][8][9][10] Although most authors emphasize the importance of avoiding cold exposure, a population based study showed that drug therapy had been attempted in more than 70% of the patients, 9 indicating that counseling is insufficient as sole therapeutic measure in a majority. The requirement for effective pharmacologic treatment is also highlighted by hemoglobin (Hgb) levels less than 8.0 g/dL in one-third and cold-induced circulatory symptoms in more than 90% of unselected patients with CAD, whereas 50% of such patients were found to have received blood transfusions during the course of the disease. 9 Corticosteroids, conventional immunosuppressive drugs and alkylating agents are generally ineffective. 6,9 Treatment with the monoclonal anti-CD20 antibody rituximab is the only well-documented effective therapy, leading to partial responses (PRs) in 45%-60% of the patients, but complete responses (CRs) are rare. 9,11,12 A median response duration of 11 months (range, 2-42 months) has been reported. 11 Although rituximab therapy is effective in polyclonal autoimmune diseases, 13,14 part of the rationale for rituximab in CAD was the demonstration of a monoclonal, B-cell lymphoproliferative bone marrow disorder in more than 90% of patients traditionally classified as having primary CAD. 4,9,11 Histologic signs of nonHodgkin B-cell lymphoma were present in bone marrow biopsy specimens from 75% of unselected patients with CAD in a population based study. 9 The most frequent type was lymphoplasmacytic lymphoma (LPL), which was found in 50% of the patients.We wanted to improve on the results achieved by rituximab single-agent therapy in patients with primary CAD. The purine analogues, eg fludarabine and cladribine, are powerful therapeutic agents in a variety of lymphoproliferative diseases. Although therapy with fludarabine for CAD has not been studied systematically, successful treatment was reported in one patient. 15 Histologic remission of the bone marrow lymphoproliferative disorder was observed after cladribine therapy in a series of 5 patients, but clinical remission was not achieved. 8 Fludarabine therapy, alone or in combination with rituximab, has yielded high response rates in Waldenström macroglobulinemia (WM), which is considered a closely related entity. [16][17][18] Furthermore, treatment with the fludarabine and rituximab combination has been found feasible and efficient in follicular lymphoma. 19 In the present study we have investigated the potential of fludarabine and rituximab in combination in patients with CAD requiring treatment. Methods Study designWe conducted a prospective, uncontrolled multicenter trial of combination therapy with fludarabine and rituximab in patients with CAD requiring An Inside Blood analysis of this article appears at the front of this issue.The publication cos...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

High response rate and durable remissions following fludarabine and rituximab combination therapy for chronic cold agglutinin disease

Berentsen

Randen

Vågan

et al. 2010

Blood

148

109

View full text Add to dashboard Cite

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“…[5][6][7] The CAs are almost invariably of the immunoglobulin (Ig) Mk class and have specificity for the I carbohydrate antigen on the erythrocyte surface. [8][9][10][11] Temperatures below normal central body temperature facilitate binding to the antigen, causing agglutination and complement-dependent hemolysis. 2,9,12 The predominant mechanism of erythrocyte breakdown, known as extravascular hemolysis, is phagocytosis of cells opsonized with complement protein C3b, generated by the classical pathway.…”

Section: Introductionmentioning

confidence: 99%

Bendamustine plus rituximab for chronic cold agglutinin disease: results of a Nordic prospective multicenter trial

Berentsen

Randen

Oksman

et al. 2017

Blood

109

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“…The first monoclonal immunoglobulin ever described was a CA from a patient with CAD (Christenson et al , 1957), and monoclonal immunoglobulin (Ig) Mκ was a recurrent finding in subsequent studies (Harboe et al , 1965). In a larger cohort of 86 patients, we detected monoclonal IgMκ in more than 90%, whereas monoclonal IgG, IgA or λ light chain restriction were rare findings (Berentsen et al , 2006).…”

Section: Clonality As Background For Therapymentioning

confidence: 99%

How I manage cold agglutinin disease

Berentsen¹

2011

Br J Haematol

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SummaryPrimary 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 fludarabinerituximab combination versus rituximab monotherapy. Patients requiring treatment should be considered for prospective trials.

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Exclusive Occurrence of k Chains in Isolated Cold Haemagglutinins

Cited by 95 publications

References 22 publications

High response rate and durable remissions following fludarabine and rituximab combination therapy for chronic cold agglutinin disease

High response rate and durable remissions following fludarabine and rituximab combination therapy for chronic cold agglutinin disease

Bendamustine plus rituximab for chronic cold agglutinin disease: results of a Nordic prospective multicenter trial

How I manage cold agglutinin disease

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