Characteristics of Late Onset Neutropenia in Rheumatologic Patients Treated with Rituximab: a Case Review Analysis from a Single Center

Background: Late onset neutropenia (LON) secondary to rituximab has been reported as an adverse event in the treatment of hematological malignancies but reports on autoimmune diseases are scarce.

Aim: To review the characteristics of LON in rheumatologic patients from a single center.

Design: Retrospective case record study.

Methods: Clinical and laboratory data since the introduction of rituximab in our clinic in 2006 were collected and analyzed retrospectively. LON was defined as an absolute neutrophil count <1.0 × 10(9)/l occurring 4 weeks after the last rituximab infusion.

Results: LON was identified in eight patients (6% of all patients receiving rituximab). All patients had complicated and refractory disease and had been treated with a median of 4.5 different immunosuppressive drugs prior to rituximab. LON appeared after a median interval of 23 weeks with recovery of LON after a median of 6.5 days. Four patients had concomitant infection at the onset of neutropenia, when six patients had both low immunoglobulin M and immunoglobulin G. Six patients were rechallenged with rituximab without recurrence of LON.

Conclusion: The characteristics of LON after rituximab treatment in patients with autoimmune disease are comparable with experiences from hematological malignancies. LON seems to precede B-cell recovery implying a perturbation of the granulocyte homeostasis. LON with its rapid recovery does not seem to increase the risk for serious infection in contrast to the sustained hypogammaglobulinemia that may follow rituximab. The risk of LON recurrence after rechallenge is low.