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Splenic marginal zone lymphoma (SMZL) is an uncommon indolent B-cell lymphoma causing marked splenic enlargement with CD20-rich lymphoma cells infiltrating blood and bone marrow. In the pre-rituximab era, the treatment of choice for patients with symptomatic splenomegaly or threatening cytopenia was splenectomy, since chemotherapy had limited efficacy. Responses to splenectomy occurred in approximately 90% of patients. However, SMZL patients are often elderly and poor surgical risks. Since approval of rituximab, treatment of such patients with the anti-CD20 antibody both alone or in combination with chemotherapy has shown remarkable responses. In retrospective series of rituximab monotherapy totaling 52 patients, including both chemotherapy-naive and -refractory patients, overall responses of 88% to 100% were noted with marked and prompt regression of splenomegaly and improvement of cytopenias. Sustained responses occurred both with and without rituximab maintenance in 60% to 88% of patients at 3 years. Relapsed patients responded to second courses of rituximab monotherapy. Overall survival was comparable to that reported following splenectomy. Rituximab in combination with purine nucleosides may provide further improvement in progression-free survival; however, confirmatory prospective trials are necessary. These results suggest that splenectomy should no longer be considered as initial therapy for SMZL but rather as palliative therapy for patients not responsive to immunotherapy with or without chemotherapy.

We previously reported durable complete responses following brief courses of rituximab and prednisone with or without cyclophosphamide in four patients with autoimmune haemophilia and inhibitor titres of 5-60 BU. We report here responses to this monoclonal anti-CD20 antibody in four additional patients, including two patients with inhibitor titres >200 BU. Factor VIII levels became normal 2-35weeks after 4 or 8 weekly doses of rituximab, brief courses of prednisone and in one patient immunoglobulin. Complete responses are ongoing at 10 months in two patients. Two patients relapsed: a patient whose initial inhibitor titre was 525 BU relapsed at 3.5 months and a long-term prednisone-dependent patient at 8.5 months. Both responded to second courses of rituximab and prednisone and are in remission. Our experience suggests that rituximab is a safe and effective addition to immunosuppression with prednisone and cyclophosphamide to treat autoimmune haemophilia, and may permit early discontinuation or even avoidance of these potentially toxic agents. High-titre inhibitor patients, however, may require multiple courses of rituximab or the addition of cyclophosphamide. Pending randomized studies, we propose an algorithm based on our experience and other reports for incorporating rituximab in the treatment of this rare disorder.

Plasma exchange is the standard treatment for thrombotic thrombocytopenic purpura (TTP). For patients refractory to plasma exchange, treatment options are limited and often unsuccessful. The platelet thrombi that form in acquired TTP are believed to result from the presence of procoagulant ultralarge multimers of von Willebrand factor (VWF) in the circulation due to autoantibody inhibition of VWF cleaving protease (ADAMTS-13), the enzyme that normally cleaves the ultralarge multimers. Rituximab, a chimeric monoclonal antibody against CD20, has been recognized as a useful therapy for antibody-mediated autoimmune disease. We therefore treated four patients with recurrent TTP with 2 or 4 weekly doses of rituximab in addition to corticosteroids, vincristine, plasma, or continuing plasma exchange. Three patients responded with prompt improvement in microangiopathic hemolytic anemia and thrombocytopenia, which allowed plasma exchange to be discontinued or avoided and prednisone to be rapidly discontinued. Two of the 3 responders have remained in unmaintained complete remission for 13+ months. The third patient relapsed at 13 months; a second course of rituximab and prednisone resulted in an unmaintained remission for 6+ months. All four patients were tested for ADAMTS-13 activity and its inhibitor at a point in their course when samples were available. Low ADAMTS-13 activity was noted in 3 patients tested at relapse, and the inhibitor activity was detectable in 2 patients. ADAMTS-13 activity increased during remission in one of these 2 patients although the patient had a persistence of the inhibitor. One patient tested only during remission had a normal ADAMTS-13 level. We conclude that rituximab may have a role and deserves further study in the treatment of patients with relapsing TTP., (Copyright 2004 Wiley-Liss, Inc.)

Autoantibodies against factor VIII (FVIII) are rare but can cause life-threatening bleeding requiring costly factor replacement and prolonged immunosuppression. We report 4 consecutively treated patients whose acquired FVIII inhibitors responded rapidly to immunosuppressive regimens that included rituximab, a monoclonal antibody against CD20(+) B cells. Three patients had spontaneously occurring inhibitors. The fourth, a patient with mild hemophilia A, developed both an autoantibody and an alloantibody following recombinant FVIII treatment. Pretreatment FVIII activities ranged from less than 1% to 4% and inhibitor titers from 5 to 60 Bethesda units (BU). One patient with polymyalgia rheumatica who developed the inhibitor while receiving prednisone responded to single agent rituximab. The hemophilia patient had rapid resolution of the autoantibody, whereas the alloantibody persisted for months. Responses continue off treatment from more than 7 to more than 12 months. This report adds to the growing evidence that rituximab has efficacy in immune disorders resulting from autoantibody formation.