Mitoxantrone is a synthetic anthracenedione that intercalates with DNA, causing cross-linking and strand breaks. Mitoxantrone also inhibits topoisomerase II, interfering with DNA repair.15- 17 This agent produces generalized immunosuppression by inhibiting the migration of monocytes and lymphocytes, inducing apoptosis in dendritic cells, decreasing secretion of proinflammatory cytokines such as tumor necrosis factor, interleukin 2, and interferon γ, inhibiting B cell function and macrophage-mediated myelin degradation, and enhancing T-cell suppressor function.18- 21 Interestingly, recent articles have indicated that mitoxantrone promotes differential inhibitory effects on the subgroups of leukocytes. First, Neuhaus and colleagues11 reported that the inhibitory effect of mitoxantrone on non–antigen-specific mitogen-activated peripheral blood T cells and B cells was significantly diminished compared with that of antigen-specific T cells. Additionally, mitoxantrone preferentially targets antigen-presenting cells.11 A previous study by Chan and colleagues12 corroborated this finding when they observed that mitoxantrone induced immediate cell death, with a predominant susceptibility of B cells, among peripheral blood leucocytes in patients with MS. Furthermore, Duddy and colleagues reported that treatment with mitoxantrone resulted in increased B-cell production of the immunoregulatory cytokine interleukin 10 and decreased production of the proinflammatory cytokines tumor necrosis factor α and lymphotoxin.13 Naive and memory B-cell subsets preferentially produce distinct effector cytokines. For example, interleukin 10 is produced almost exclusively by naive B cells, whereas lymphotoxin and tumor necrosis factor α are largely produced by memory B cells.13 The current results correspond with those of previous articles in which mitoxantrone preferentially inhibited B cells, especially memory B cells, in patients with NMO. Considering that humoral immunity plays a pivotal role in the pathogenesis of NMO, preferential depletion of effector B cells by mitoxantrone provides the immunological background to explain the clinical effect without complications such as severe infection due to global immunosuppression.