Cold Agglutinin Disease Medication

  • Author: Sharon Georgy, MD; Chief Editor: Michael A Kaliner, MD   more...
 
Updated: Nov 15, 2010
 

Medication Summary

Folic acid supplementation is advisable in individuals with cold agglutinin disease to meet the increased requirements of increased RBC production due to hemolytic anemia.

Immunosuppressive and immunomodulating drugs are seldom necessary; however, in cases with underlying malignancies, these agents are required to treat the malignancy. Potent immunosuppression to reduce the production of monoclonal antibody and to reduce/eliminate the abnormal lymphocyte clone has been achieved with cyclophosphamide (1200 mg) and vincristine (2 mg) administered intravenously (IV) on day 1 and prednisone (80 mg/d) administered orally (PO) for 5 days, with some beneficial effect in an anecdotal case.[17] The same patient was treated 10 months later with IV fludarabine (25 mg/m2) daily for 5 days and then every 28 days for 3 courses. Following a third course of treatment, the patient went into remission that lasted at least 4 years.[17]

Rituximab has been widely recognized as being very effective for treating cold agglutinin disease. One study documented a high response rate and durable remissions following therapy using a combination of fludarabine and rituximab. While the results from this study appear positive, extreme caution should be exercised as the immunosuppressive effects of rituximab superimpose on those of fludarabine.[52]

Bear in mind that one uncommon reported adverse effect of fludarabine is the appearance of a warm autoantibody–induced autoimmune hemolytic anemia. However, according to the authors' experience, persons with Coombs-positive hemolytic anemias have been treated effectively with fludarabine. Responses to interferon alfa therapy have been reported. This therapy may be useful for some B-cell neoplasms.[53]

Chlorambucil has also been used to treat cold agglutinin disease.[54] Corticosteroids alone may not be routinely useful in all patients with cold agglutinin disease, although occasionally a patient may have a clinical response. Patients with mixed cold and warm immune hemolytic anemia are more likely to have a response because of the warm antibody component.

In general, use of chemotherapeutic agents, which have long-term consequences for the patient and are associated with secondary malignancies such as leukemias that are hard to treat, requires very careful decision making in collaboration with a well-informed patient. These agents should be used only for life-threatening, severely symptomatic disease. Therapy also may need to be administered intermittently or infrequently, as the case demands. Tailor therapy to individual needs. Only currently used drugs are discussed. These will change as newer drugs become available for use.

Although alkylating agents have been used in the past and references to these treatments are part of standard texts, the authors suggest that these drugs not be used in patients with cold agglutinin disease because of the potential for long-term adverse effects of such therapy for an essentially benign disorder.

The reader is advised to read the package insert approved by the US Food and Drug Administration (FDA) before using any of the agents listed.

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Immunosuppressive Alkylating Agents

Class Summary

The metabolites of immunosuppressive alkylating agents cross-link DNA, thereby interfering with cell proliferation. These agents are not needed in patients with idiopathic cold agglutinin disease.

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Cyclophosphamide (Cytoxan)

 

Chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells. Cystitis can develop with long-term administration; the leukemogenic potential should be kept in mind. Primary (idiopathic) form of the disease is unlikely to require use of this class of drugs.

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Glucocorticoids

Class Summary

Glucocorticoids are used for their immunosuppressant properties.

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Prednisone (Deltasone, Sterapred, Meticorten)

 

Immunosuppressant for treatment of autoimmune or lymphoproliferative disorders. Modulates lymphocytes and decreases antibody production. Frequently used with alkylating agents.

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Interferons

Class Summary

Interferons have had variable success in cold agglutinin–induced hemolytic anemia. Expense and serious adverse effects are issues to consider up front before choosing this class of drug. Interferons are used in the treatment of lymphoproliferative disorders.

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Interferon alfa-2b (Intron-A)

 

Identifying the proper drug for use in a patient depends on patient characteristics and patient participation in the decision-making process. No guarantees of success can be given with any therapy in cold agglutinin disease. Interferon alfa is manufactured by recombinant DNA technology. Mechanism of effect is not clearly understood. However, direct antiproliferative effects against many different kinds of malignant cells have been shown in clinical disease states (eg, lymphoma, melanoma, CGL) and modulation of host immune response may play important roles.

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Vitamin, Water Soluble

Class Summary

Water-soluble vitamins are necessary for hematopoiesis.

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Folic acid (Folvite)

 

Important cofactor for enzymes used in the production of RBCs. Chronic hemolytic process requires additional folate.

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Immunosuppressant Agent

Class Summary

Immunosuppressant agents include antibodies that are directed against the CD20 antigen found on the surface of B-lymphocytes.

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Rituximab (Rituxan)

 

Effective lowering of IgM and IgG levels is achievable with this anti – B cell antibody. Hypersensitivity reactions can be severe; users of the drug should become completely familiar with the adverse reactions known to occur.

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Contributor Information and Disclosures
Author

Sharon Georgy, MD  Resident Physician, Department of Internal Medicine, University of South Florida

Sharon Georgy, MD is a member of the following medical societies: Phi Beta Kappa

Disclosure: Nothing to disclose.

Coauthor(s)

Richard F Lockey, MD  University Distinguished Health Professor, Professor of Medicine, Pediatrics and Public Health, Joy McCann Culverhouse Chair in Allergy and Immunology, University of South Florida College of Medicine; Director, Division of Allergy and Immunology, James A Haley Veterans' Hospital

Richard F Lockey, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Allergy Asthma and Immunology, American Association for the Advancement of Science, American College of Chest Physicians, American College of Occupational and Environmental Medicine, American College of Physicians, American Medical Association, and Florida Medical Association

Disclosure: Nothing to disclose.

Rajalaxmi McKenna, MD, FACP  Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Harry L Messmore, Jr, MD  Professor, Department of Medicine, Division of Hematology/Oncology, Loyola University Stritch School of Medicine

Harry L Messmore, Jr, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Angiology, American College of Physicians, American Heart Association, American Society of Hematology, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Specialty Editor Board

Jeffrey Lee Kishiyama, MD  Assistant Clinical Professor of Medicine, University of California, San Francisco, School of Medicine; Consulting Staff, Allergy and Asthma Associates of Santa Clara Valley Research Center

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

Samuel R Marney, Jr, MD  Director, Associate Professor, Department of Internal Medicine, Division of Allergy and Immunology, Vanderbilt University School of Medicine

Samuel R Marney, Jr, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology, American College of Physicians, and Tennessee Medical Association

Disclosure: Nothing to disclose.

Timothy D Rice, MD  Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, St Louis University School of Medicine

Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians

Disclosure: Nothing to disclose.

Chief Editor

Michael A Kaliner, MD  Clinical Professor of Medicine, George Washington University School of Medicine; Chief, Section of Allergy and Immunology, Washington Hospital Center; Medical Director, Institute for Asthma and Allergy

Michael A Kaliner, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Allergy, Asthma and Immunology, American Society for Clinical Investigation, American Thoracic Society, and Association of American Physicians

Disclosure: Alcon Consulting fee Consulting; Greer Consulting fee Consulting; Sanofi Consulting fee Consulting; Schering/Merck Consulting fee Consulting; Teva Consulting fee Consulting; Meda Honoraria Speaking and teaching; Ista Consulting

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Peripheral blood smear showing several clumps of RBCs with the largest in the center. These are typical of aggregates seen in persons with cold agglutinin disease.
 
 
 
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