[Treatment of severe idiopathic cold-agglutinin diseases using interferon-alpha 2b]

Cold agglutinin disease is an immunohemolytic anemia in which the autoantibody directly agglutinates human red blood cells below body temperature, maximally at 0 to 5 degrees C. The disease is considered to occur in primary (idiopathic) or secondary forms. The secondary form is noticed in the setting of infections (e.g. Mycoplasma pneumoniae, infectious mononucleosis), or patients with lymphoproliferative disorders. Affected patients show varying clinical presentation ranging from mild to serious hemolytic anemia, episodic hemoglobinuria, acrocyanosis, or other peripheral vaso-occlusive events which are all occasioned by cold exposure. In mild chronic cold agglutinin disease preventing cold exposure usually suffices to avoid disease exacerbation. However, treatment of severe disease is difficult. Splenectomy or glucocorticoids are generally disappointing, but exceptions have been reported. Treatment with alkylating agents, as for example chlorambucil or cyclophosphamide, may be effective in some patients. However, late effects, and in particular their carcinogenic potential when used as long-term treatment, must be born in mind. We report on a 59-year-old woman with severe cold agglutinin disease who was at first treated successfully with chlorambucil and prednisone. Based on in vitro evidence, primary cold agglutinin disease can be considered as a low grade malignant lymphoproliferative disorder in which interferon-alpha has been shown to be an effective therapeutic agent, at least in forms such as hairy cell leukemia. We therefore switched therapy to interferon-alpha 2b (three million units/m2 body surface area subcutaneously three times weekly). 18 months after treatment initiation there was no remission, but improvement of clinical and laboratory signs of the disease was noted.(ABSTRACT TRUNCATED AT 250 WORDS)