Sustained Response to Anti-CD20 Monoclonal Antibody in Severe Acute Primary Immune Thrombocytopenic Purpura: Report of One Adult Case

The usefulness of anti-CD 20 monoclonal antibody (rituximab) has been reported in chronic forms of immune thrombocytopenic purpura (ITP) lasting months to years. We administered rituximab 375 mg/m2 weekly × 4 in the acute phase of severe symptomatic adult primary ITP refractory to different therapies over a 30 days period. Platelet count began to rise after the third injection and subsequently fully recovered and stabilized with a follow-up of 16 months to date, suggesting the potential utility of rituximab also in selected cases of acute primary ITP. There is still a lack of firm evidence on management strategies for adult primary immune thrombocytopenic purpura (ITP) not responding to first-line therapy and also due to side effects of second-line drugs (1). Anti-CD20 monoclonal antibody (Rituximab) has been reported to be safe and useful in chronic refractory or relapsing ITP (2). In primary forms it has been used months to years after the onset of disease (3–5). We report here the case of severe symptomatic ITP occurring in a 24-year-old man who was successfully given rituximab 30 days after disease onset and failure of 5 different lines of therapy (Fig. 1). A previously healthy 80-kg white worker was referred to us on January 21, 2003, because of petechiae and easy bruising since the previous week. His personal history was unremarkable. Physical examination disclosed several large hematomas both at the limbs and trunk and fine petechiae involving the oral mucosa and legs. No splenomegaly or lymph node enlargement was observed. Platelet count was 8 × 109/L. A bone marrow aspirate was rich in megakaryocytes. The diagnosis of primary ITP was made based on the absence of multisystem autoimmune disease, lymphoproliferative disorders, myelodysplastic syndromes, drug-induced thrombocytopenia, chronic liver disease, and viral and bacterial infection. Despite the administration of different combined or sequential therapies, as summarized in the Figure, platelet count failed to improve. Namely, steroids, i.v. immunoglobulin (Ig), plasmapheresis, oral cyclophosphamide, and danazol were ineffective, the last being stopped also because of liver enzyme elevation. Further treatment was deemed necessary owing to several episodes of headache, hematochezia, and epistaxis, in addition to continuing easy bruising and petechiae, without platelet count increase after platelet transfusion. On February 20, 2003, following premedication with acetaminophen 500 mg and chlorpheniramime 10 mg, rituximab (Mabthera, Roche, Milan), 375 mg/m2, was infused in saline at a final concentration of 1.5 mg/mL, four times at 1-week interval, starting each time at 50 mg/hour, with subsequent infusion rate increase up to 200 mg/hour, without side effects. Hemorrhagic mucocutaneous manifestations disappeared along with platelet count recovery between the third and fourth cycles. Platelet count rose to 132 × 109/L at 30 days and reached fully normal values in August 2003. Prednisone was tapered until withdrawal in October. Complete response persists 16 months after rituximab administration with no evident side effects. A spontaneous recovery cannot be excluded. However, the relationship between rituximab administration and platelet count increase, together with the unusual resistance to previous therapy, make such an hypothesis less likely. The