Refractory Autoimmune Cytopenias, Either Associated with Lymphoproliferative Diseases or Idiopathic in Adult Patients, Treated with Anti-CD20 Monoclonal Antibody (Rituximab).

Immune cytopenias (IC) frequently require prolongued administration of immunosupressors, especially when associated with lymphoproliferative disorders (LPD). Rituximab causes in vivo selective destruction of B lymphocytes and supresses the production of antibodies. Three mechanisms are involved; complement dependent cytotoxicity, antibody dependent cellular citotoxicity and the induction of apoptosis. We present 10 patients with IC: 8 autoimmune hemolytic anemia (AIHA), and 2 AIHA plus immune thombocytopenia (Evans’ syndrome). Seven patients had IC associated with LPD, and 3 were idiopathic. LPD were: 3 follicular lymphoma (1 Grade 1, 1 Grade 2, 1 Grade 3), 1 small lymphocytic lymphoma, 3 chronic lymphocytic leukemia. Three patients with idiopathic cytopenias had a long history of recurrent AIHA (2) and Evans’ syndrome (1). Ages ranged between 43 and 81 (median 63 yrs); 6 were female gender and 4 male. All AIHA cases, except 1 pts with cryogrobulins, presented with warm IgG antibodies. Previous evolution included splenectomy in 2 pts and all pts received multiple courses of immunosupression with steroids and others, like azathioprine and cyclophosphamide. All patients with LPD received one or more chemotherapeutic regimens with alkylating agents, fludarabine or CHOP combination. Median time to IC in 7 pts with LPD was 75 months (2–228). Idiopathic cases had 12, 132 and 204 months of previous evolution. Rituximab was administered at 375 mg/m2 every 1 to 3 weeks for 3 to 8 doses (median 4). Six pts received rituximab as monotherapy and 4 pts in combination with chemotherapy. Toxicity was mainly related to the first cycle of rituximab and consisted in chills and fever grade I-II in three pts. Clinical resolution of cytopenia occured in 9/10 pts (90%). 4 of them (44%) resolved with negative direct antiglobuline test. Median time to response was 4 weeks (2–8). One AHIA died with hemolysis progression, six months after rituximab, and 1 pts with AHIA and follicular lymphoma died 8 months after rituximab treatment with progression of LPD without evidence of hemolysis. The rest of the patients remained without IC for 2–42 months (median 18). Rituximab, originally designed to treat B-cell neoplasms, is an active immunosupressive agent in either lymphoproliferative associated or idiopathic autoimmune cytopenias even in non splectomized pts. Its use may avoid the secondary effects of long term administration of steroids, alkylating agents or transfusions.