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Commentary (Cheson): Rituximab in the Treatment of Autoimmune Hemolytic Anemia

Commentary (Cheson): Rituximab in the Treatment of Autoimmune Hemolytic Anemia

Based on its B-cell-depleting properties, rituximab as a single agent or in combination with immunosuppressive chemotherapy drugs has been used to successfully treat nonmalignant hematologic conditions such as immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia, cold agglutinin disease, and pure red cell aplasia (Hegde et al: Proc Am Soc Clin Oncol 20:305a[abstract 1218], 2001; Perrota and Abuel: Blood 92:88b[abstract 3360, 1998; Saleh et al: Blood 96:252a[abstract 1086], 2000; Lee et al: Blood 96:596a[abstract 2560], 2000; Rai et al: Blood 96:754a[abstract 3264, 2000; Zecca et al: Blood 97:3995-3997, 2001; Stasi et al: 98:952-957, 2001), with encouraging success. Anecdotal reports also suggest activity for rituximab in systemic lupus erythematosus, rheumatoid arthritis, inflammatory arthropathy, and paraneoplastic pemphigus (Edwards and Cambridge: Rheumatology 40:205-211, 2001; Protheroe et al: Rheumatology 38:1150-1152, 1999; Heizmann et al: Am J Hematol 66:142-144, 2001).

ITP is an autoimmune disorder that may occur alone or in association with a malignant disorder such as CLL. Corticosteroids have been the standard treatment for most patients with ITP, but with long-term benefit in only about 20% of patients. For the remaining patients, treatment options include intravenous immunoglobulins, danazol, and splenectomy, none of which is uniformly effective. Cooper et al (abstract #2180) reported their experience with 21 adult patients with immune thrombocytopenic purpura and platelet counts less than 30,000/µL treated with the standard dose and schedule of rituximab. Of the 14 patients followed for at least 10 weeks, 57% achieved a platelet count greater than 50,000/µL, with a durable complete remission in five of the eight responders.

The promising results from several small studies and anecdotal experiences support the earlier use of rituximab in this indication, as it is preferable to chronic steroid administration, intravenous immunoglobulins, or splenectomy. Rituximab-based regimens are also an active treatment for autoimmune hemolytic anemia (Lee et al: Blood 96:596a[abstract 2560], 2000; Gupta et al: Blood 98:363a[abstract 1529], 2001). Polyclonal antibodies directed against red cell antigens (eg, anti-D) are active in ITP, and in vitro data suggest that monoclonal antibodies directed at red cell antigens might be effective as well (abstract #1849, Lazarus et al).

Pure red cell aplasia is an uncommon complication of CLL. Treatment has included corticosteroids or treatment for the underlying disease. Responses can also be achieved with cyclosporine (Neoral, Sandimmune). A combination of rituximab, corticosteroids, and cyclophosphamide has been useful in treating this complication and at the time of its recurrence (abstract #914, Ghazal et al). Whether this combination is more effective than rituximab alone is not known.

Another potential indication for rituximab is to treat patients with an acquired antibody against coagulation factors. Ege and Besa (abstract #2241) reported an anecdote of a patient with a circulating anticoagulant to von Willebrand factor who did not respond to steroids. Two cycles of rituximab resulted in normalization of the coagulation parameters. Other reports (abstracts #2232, Karwal et al; #2233, Wiestner et al) show activity in patients with an anti-factor VIII antibody.

 

 
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