title: Rituximab associated late-onset neutropenia-a rheumatology case series and review of the literature.
abstract: Recently in the rheumatology literature, Rituximab (RTX) has been associated with late-onset neutropenia (LON), defined as an absolute neutrophil count (ANC) <1.5 × 10(9)/L at least 4 weeks after the last infusion. We determined the incidence of LON in patients with rheumatic disease at a single tertiary medical center, ascertained patient characteristics including results of bone marrow biopsies performed on four neutropenic patients, and performed a literature review. The incidence at our institution was 6.5 %, similar to that reported in the literature. Bone marrow biopsies from four neutropenic patients had the predominant cell line as lymphocytes, comprising an average of 41 % (range 24-50 %) of the cellular aspirate suggesting that there is a selective reduction in granulopoiesis and maturation arrest at the promyelocyte stage. Sixty percent of patients presented without serious infections, and all survived without adverse sequelae. Treatment with granulocyte colony-stimulating factor shortened time to recover of ANC but did not change overall outcomes. Among 25 patients re-challenged with RTX after resolution of LON, only two developed recurrence of LON. Among patients at our institution and identified from a review of the literature, LON is not usually associated with serious infections that lead to significant adverse outcomes, G-CSF therapy does not appear to be necessary as it does not change outcomes, and RTX re-treatment after recovery from LON appears safe.
authors.affiliation: Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH, 03756, USA. william.e.monaco@hitchcock.org.
authors.forename: William E
authors.initials: WE
authors.lastname: Monaco
authors.affiliation: Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH, 03756, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Jones
authors.affiliation: Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH, 03756, USA.
authors.forename: William F C
authors.initials: WF
authors.lastname: Rigby
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced* / Q000453:epidemiology; D012189:Retrospective Studies; D012216:Rheumatic Diseases / Q000188:drug therapy*; D000069283:Rituximab / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D018501:Antirheumatic Agents; D000069283:Rituximab
keywords: Late-onset neutropenia; Rheumatic diseases; Rheumatoid arthritis (RA); Rheumatology; Rituximab