Lack of clinical efficacy of rituximab in the treatment of autoimmune neutropenia and pure red cell aplasia: implications for their pathophysiology

Abstract

We describe 11 patients with severe refractory autoimmune cytopenias treated with the anti-CD20 monoclonal antibody rituximab. Six patients had autoimmune neutropenia (AIN), two had pure red cell aplasia (PRCA), one had AIN and autoimmune haemolytic anaemia, one had AIN and immune thrombocytopaenia purpura (ITP) and one had PRCA and ITP. Rituximab was administered at a dose of 375 mg/m(2) as an intravenous infusion weekly for 4 weeks. Six of eight patients with AIN and all three patients with PRCA did not respond. Two patients died: one with resistant AIN and autoimmune haemolytic anaemia died of pneumocytis pneumonia infection, and one with PRCA and ITP died of an acute exacerbation of bronchiectasis. Rituximab in AIN and PRCA appears to be less effective than Campath-1H when compared to historical data from our group. This supports the hypothesis that T cells may be important in the pathophysiology of AIN and PRCA.

Disease-Specific Complications of Chronic Lymphocytic Leukemia

“…Rituximab has been successful in the treatment of PRCA 41 but another study noted that it was less effective in refractory autoimmune neutropenia. 42 Nonhematological autoimmune phenomena Autoimmune conditions affecting nonhematological tissues are rare but well-described, and in some instances have been precipitated by therapy ( Table 3). Numerous antibodies can be detected serologically in CLL patients but only infrequently correlate with clinical disease.…”

Thymoma with Concomitant Pure Red Cell Aplasia, Good’s Syndrome and Myasthenia Gravis Responding to Rituximab

“…Several reports have shown successful treatment of PRCA with rituximab in patients with B cell lymphoproliferative disorders, mostly chronic lymphocytic leukemia [15,16]. Conversely, results of rituximab therapy have been disappointing in patients with severe, resistant and life-threatening PRCA refractory to conventional immunosuppression, as in idiopathic PRCA [17]. To our knowledge, our patient represents the first reported case of a thymoma with three associated paraneoplastic autoimmune disorders, namely PRCA, Good's syndrome, and myasthenia gravis responding to anti-CD20 therapy, namely rituximab.…”

Rituximab for the treatment of autoimmune cytopenias

“…40,41,93 Success has been reported in single cases of PRCA complicating CLL, 91,92 AIN in immunodeficient children, 40 and AIN combined with ITP. 90 Results of rituximab therapy have been disappointing, however, in several other cases of AIN and PRCA.…”

“…90 Results of rituximab therapy have been disappointing, however, in several other cases of AIN and PRCA. 93 A more important role of T-cell abnormalities as compared to humoral autoimmunity has been proposed as an explanation, 93,94 although such statements are uncertain in these heterogeneous and rare conditions.…”