In 1997, rituximab was approved by the US Food and Drug Administration (FDA) as a treatment for non-Hodgkin’s lymphoma of B cell that was resistant to chemotherapy. After that, it was applied for treatment for other diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Wegener’s granulomatosis, idiopathic thrombocytopenic purpura (ITP), and Sjögren’s syndrome. Ten years later, its impact on the treatment of blister diseases such as pemphigus was shown [1].

In a 2006 study by Larrar et al., two children with autoimmune hemolytic anemia who were treated with rituximab experienced acute thrombocytopenia and neutropenia [2]. They resolved in several days, which showed that these hematologic effects are directly dependent on the toxicity of rituximab.

In a study by Chairwatanatorn et al. in 2003, neutropenia following application of rituximab was tested in 53 patients [3]. All patients except one were under Hodgkin’s lymphoma treatment. Eight cases of grade 4 neutropenia were observed after 1–5 months of rituximab treatment (five patients only received rituximab and three patients were also under additional chemotherapy); three patients advanced toward sepsis. Neutropenia was not related to other diseases or treatments and was related with reduction of neutrophil precursors, except for one of the patients whose bone marrow had hypoplasia. All cases of neutropenia occurred among the patients whose polymorphonuclear neutrophils (PMN) were normally or weakly reduced [3].

In a study by Tesfa et al. in 2008, neutropenia occurred 4 or more weeks after rituximab treatment in lymphoma patients [4]. However, the mechanism of how rituximab causes neutropenia is still unknown. In a retrospective study of 113 lymphoma patients under rituximab treatment (alone or along with chemotherapy), eight patients (7%) had neutropenia. The average onset was 88 days after receiving their last dosage of rituximab. The average time interval of neutropenia was 54 days. Four of the eight patients underwent stem cell transplantation, three patients had neutropenia with fever, and two of them needed granulocyte colony-stimulating factor (G-CSF) treatment. In the patients who had neutropenia, a cessation in maturation was observed in the promyelocytes category (the same as congenital neutropenia or Kostmann disease) [4].