Elsevier

Seminars in Hematology

Volume 47, Issue 2, April 2010, Pages 180-186
Seminars in Hematology

Rituximab-Associated Neutropenia

https://doi.org/10.1053/j.seminhematol.2010.01.009Get rights and content

Several recent studies have reported the phenomenon of late-onset neutropenia occurring usually several months following the administration of rituximab or rituximab-based therapies. While it appears that late-onset neutropenia is usually not clinically significant and is self-limited, it is important to recognize its existence given the expanding use of rituximab in both hematologic and nonhematologic disorders. Late-onset neutropenia is intriguing biologically and while its pathogenesis and mechanism are not completely understood, many interesting hypotheses have been proposed to explain its occurrence.

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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