Rituximab-associated agranulocytosis in children with refractory idiopathic nephrotic syndrome: case series and review of literature

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Agranulocytosis has been reported as a delayed-onset complication of rituximab treatment. However, the exact incidence and risk factors of this complication in patients with nephrotic syndrome remain unknown.


Records of 213 rituximab treatments for 114 patients with refractory nephrotic syndrome between February 2006 and April 2013 were reviewed to identify episodes of agranulocytosis (defined as an absolute neutrophil count of <500 mm3).


Eleven episodes of agranulocytosis were detected in 11 patients. Median time of onset of agranulocytosis was 66 days (range, 54–161 days) after rituximab treatment. Nine patients experienced acute infections and received antibiotics. All but one patient received granulocyte colony-stimulating factor. Agranulocytosis resolved in all cases within a median of 3 days. The incidence of agranulocytosis was 9.6% in total patients and 5.2% in all treatments. Median age of the 11 patients who developed agranulocytosis was 6.4 years at the first rituximab treatment, significantly younger than the median age of the 103 patients who did not (median, 12.5 years; P = 0.0009). Five patients received re-treatment with rituximab. No recurrence of agranulocytosis was observed in any patient.


It is important to pay extra attention to this clinically serious delayed-onset complication as it may be accompanied by life-threatening infections such as sepsis. Further clinical studies are needed to clarify its pathogenesis.

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