Rituximab in autoimmune pancytopenia: a case report and review of literature

Dear Editor, The possibility of eliminating autoreactive B cell clones with the chimeric monoclonal antibody rituximab has made it an attractive treatment for antibody-mediated autoimmune disorders. There has been growing interest in its use in idiopathic-relapsing thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA). There has been little data on using this agent in autoimmune neutropenia. We present a case of autoimmune pancytopenia successfully treated with rituximab. The patient is a 39-year-old White female with a history of autoimmune hepatitis. Her ANA was 1:320, alkaline phosphatase was 173 IU/l, AST was 127 IU/l, and ALT was 97 IU/l. Her hepatitis B and C serologies were negative. A liver biopsy revealed a portal mononuclear infiltrate. Her autoimmune hepatitis was initially treated with prednisone followed by 1 year of azathioprine therapy. Her blood counts were all within normal limits during this treatment period. Ten days after having normal blood counts, she was found to be pancytopenic. Her granulocyte count had decreased to 0.4×10/l, hemoglobin was 5.0 g/dl, and platelets were 9.0×10/l. Azathioprine was stopped at this time. She developed oral bleeding and leg bruising, which required red blood cell and platelet transfusions. She was started on pegfilgrastim and epoetin alpha; however, there was only minimal improvement in her white blood cell count and she continued to require packed red blood cell transfusions approximately every 2 weeks. A bone marrow biopsy revealed a hypercellular marrow with increased megakaryopoiesis indicating a high platelet, erythroid, and myeloid turnover rate. Flow cytometry and molecular cytogenetics were unremarkable. She was subsequently referred to Thomas Jefferson Hematology for further management. On her initial visit, she complained of right upper quadrant pain, oral blood blisters, and ecchymoses. Her physical exam was significant for pallor, two small areas of bleeding on the left buccal mucosa, scattered ecchymoses on her extremities, and tender hepatomegaly 1.5 cm below the costal margin. There were no swollen joints, rash or palpable splenomegaly. Laboratory evaluation was consistent with a hemolytic process. Her haptoglobin was <35 mg/dl and her lactate dehydrogenase was 1,235 IU/l. Her direct antiglobulin test revealed a monospecific anti-IgG and the eluate was reactive with all reagent red cells, consistent with an AIHA. Her granulocyte immunofluoresence test (GIFT) was reactive for direct granulocyte antibodies. The patient was started on prednisone 60 mg daily. Her granulocyte and platelet counts increased to 1.9×10/l and 115×10/l, respectively, but fell when the steroids were tapered. She continued to require regular blood transfusions. Her granulocyte count was 2.0×10/l, hemoglobin was 8.1 g/dl, and platelet count was 7.0×10/l. She was subsequently treated with 4 weekly cycles of rituximab 375 mg/m, which she tolerated well. There was a rapid improvement in the peripheral blood counts seen 1 week after treatment. Her platelet count increased to 115×10/l. Her blood counts peaked at 8 weeks and remained stable. Her subsequent Coombs test and granulocyte antibody tests were negative. Three months after her first round of rituximab, she had a second relapse. Her granulocyte count fell to 0.3×10/l, her Ann Hematol (2007) 86:913–916 DOI 10.1007/s00277-007-0316-4