Anti-CD20, a chimeric monoclonal antibody (rituximab), binds avidly to the CD20 antigen, which is expressed almost exclusively on the surface of B-cells in different stages of their development. The observed elimination of B cells from serum and lymphoid tissue of patients treated with anti-CD20 suggests that this agent could have a beneficial effect in immune diseases such as chronic immune thrombocytopenic purpura (cITP), autoimmune hemolytic anemia or hemophilia with inhibitors. Anti-CD20 was given to two children with refractory cITP and another two with hemophilia and FVIII inhibitors. All 4 children had frequent admissions to the hospital and poor quality of life. Anti-CD20 was administered at a dose of 375mg/m2, once weekly, for 4 consecutive weeks. B cells were measured in peripheral blood with monoclonal antibodies CD19 and CD20, before induction of treatment and in certain time-points after drug administration. Case 1: A 5 2/12-year old girl with cITP, diagnosed at the age of 2 3/12, presented with profound thrombocytopenia and recurrent hemorrhages from several systems, including CNS. She was refractory to any available therapy, therefore an unsuccessful splenectomy was performed at the age of 3 6/12. Following splenectomy, she continued to be severely thrombocytopenic and symptomatic, not responding even to immunosuppressive agents. Patient received anti-CD20, three years from the onset of the disease. Case 2: A 7 4/12 -year old boy was diagnosed as having ITP at the age of 5 9/12. Due to frequent bleedings, not responsive to the available therapy plus azathioprime, he was administered anti-CD20 to postpone splenectomy. Case 3 and 4: Two severely affected hemophiliacs (F VIII<1 u/dl) with high responding inhibitors (maximum titers 17.6 and 80 BU), aged 13 6/12 and 3 7/12 years respectively, received rituximab to possible reduce the inhibitor titer to<5 BU in order to initiate immune tolerance therapy (ITT).
Results: Both cITP patients initially increased their platelet values to 90′109/L and 40′109/L respectively for the first three months. 17 and 9 months from the initiation of the rituximab, children were asymptomatic, although they presented with fluctuations of the platelet values (10–30′109/L). Both hemophiliacs reduced their inhibitor titer to 4.8 BU and 4.0 BU respectively, therefore ITT was applied. Case 3, lost the antibody within 21 days and he has been on successful prophylactic therapy for the last 6 months. Case 4 had an initial increase in titer, followed by a decline. Despite the frank reduction of CD-19 and CD-20 B-cells, none of the patients suffered any infection.
Conclusion: Anti-CD20 seems to be an optional therapeutic tool for children with refractory cITP or hemophiliacs with high titer inhibitors, in case ITT has to be applied. Although patients may have a poor laboratory response, they acquire a better quality of life minimizing hospital admissions. However, long-term complications have to be studied in a larger scale.