Rituximab associated neutropenia: Description of three cases and an insight into the underlying pathogenesis

BACKGROUND: To describe Rituximab associated neutropenia (RAN), and to explore its underlying mechanism. CASE REPORT: We describe three patients with RAN. The effect of patient's plasma on colony forming unit, Granulocyte-Monocyte (CFU-GM) was measured by the addition of plasma to the culture of a healthy bone-marrow. Repeated tests were performed after recovery of white count. In the leukopenic period the patient's plasma inhibited CFU growth completely. Control plasma did not have such an effect. Addition of patient's cell supernatant to bone marrow cells did not change the number of CFU. The same effect was demonstrated in normal control. After recovery the patient's plasma did not inhibit colony formation, similar to control. CONCLUSIONS: RAN is a clinically significant side effect. It may take place during treatment or several months afterwards. Circulating antibodies in the plasma may be responsible for this unique BM toxicity.