Rituximab-Associated Neutropenia
Section snippets
Incidence and Onset of Late-Onset Neutropenia Following Rituximab
Late-onset neutropenia following rituximab has now been reported by a number of groups (Table 1).9, 13, 14, 15, 16, 17, 18, 19 In our study, we evaluated 153 previously untreated patients treated on DA-EPOCH (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) protocols at the National Cancer Institute (NCI) and included the histologies diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and Burkitt lymphoma (BL).9 To control for confounding causes of
Postulated Mechanisms of Late-Onset Neutropenia: Granulocyte Homeostasis and the Role of SDF-1/CXC Ligand 12
Several mechanisms for late-onset neutropenia following rituximab have been postulated but currently there is no direct evidence for one mechanism. While we have hypothesized that it may be related to perturbations in SDF-1 levels at the time of B-cell recovery interfering with neutrophil egress from the bone marrow, others have postulated alternative mechanisms including neutropenia due to autoantibody production following rituximab treatment and the expansion of T-LGL populations that may
Granulocyte Inhibition/Destruction
Several other mechanisms of late neutropenia following rituximab have been proposed by other groups. Papadaki et al reported the occurrence of neutropenia following rituximab treatment in patients who showed evidence of LGLs in the peripheral blood and bone marrow.12, 20 These were characterized by a predominance of CD3+CD8+CD57+CD28− T cells. The authors hypothesized that LGLs caused neutropenia through CD95-induced apoptosis caused by Fas and Fas-ligand secretion by LGLs in addition to Fas
Conclusions
Late-onset neutropenia following rituximab therapy is not uncommon and is likely to be significantly underdetected. While rituximab has been associated with the development of neutropenia early after administration and following high-dose therapy, the pathogenesis of late-onset neutropenia appears to be unique and distinct. Given the wide use of rituximab in the management of B-cell disorders and its ever-increasing indications in autoimmune and other diseases, it is important to recognize this
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