2-Chlorodeoxyadenosine (2-CdA) has been shown useful in the treatment of Waldenstrom's macroglobulinemia, a B-cell lymphoma that secretes a monoclonal IgM antibody. However, 2-CdA has not proven useful in patients with multiple myeloma, a tumor tha secretes IgG. We are testing the hypothesis that 2-CdA can be used to treat patients with autoimmune disease in association with an IgM or IgA paraprotein, but who do not fulfill criteria for a lymphoma. Patients we have treated during the past 2 years have had the following medical conditions: progressive motor neuropathy with monoclonal anti-GM1 antibody (partial remission), vasculitis due to type II mixed cryoglobulinemia with monoclonal rheumatoid factor (full remission), vasculitis due to monoclonal cold agglutinin (full remission), vasculitis due to type I IgM cryoglobulinemia (full remission in 1 case). We hypothesize that 2-CdA is most effective in patients with autoimmune features in association with IgM paraproteins. We continue long-term followup on patients previously treated in the protocol and to treat patients with IgM paraproteins associated with vasculitis. Bone marrow aspirates will be used to establish human monoclonal antibodies by a recombinatorial DNA method to allow direct comparison of the pathogenetic antibody in vivo and the antibody reconstructed by recombinatorial methods. Precise mapping of the antigenic epitope seen by the pathogenetic antibody will allow better understanding of pathogenesis and better methods to monitor therapy.
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