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Abstract Number: 567

Rituximab Associated Late Onset Neutropenia – a Rheumatology Case Series and Review of the Literature

William Monaco1, William F.C. Rigby2 and Jonathan Jones3, 1Internal Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH, 2Geisel School of Medicine at Dartmouth, Lebanon, NH, 3Rheumatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: neutropenia, outcomes, Rheumatoid arthritis (RA), rituximab and treatment

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Session Information

Date: Sunday, November 8, 2015

Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Rituximab (RTX) has been associated with late onset neutropenia (LON), defined as an absolute neutrophil count (ANC) < 1.5 x 109/L at least 4 weeks after the last infusion.  Reports of LON are primarily found in the hematology literature.  We determined the incidence of LON in patients with rheumatic disease at a single tertiary medical center, ascertained patient characteristics, and performed a literature review.

Methods: We performed a retrospective study of patients at Dartmouth-Hitchcock Medical Center that received RTX for a rheumatologic disease between 2006-2014 and developed LON.  In addition, we reviewed 4 case series of LON after RTX was given for rheumatologic disorders.

Results: We found 11 patients who developed LON (6 male and 5 female, average age 63), which was 6.5% of 168 patients receiving RTX.  The most common diagnosis was RA (9 LON patients and 73% of all patients who got RTX).  The average time to LON after RTX therapy was 90 days (range of 40 to 198 days).  The average ANC nadir was 0.5 x 109/L, and while 3 patients received granulocyte colony-stimulating factor (G-CSF), all patients’ neutrophil counts normalized.  The median total dose of RTX prior to LON was 5 gms.  4 patients presented with an infection (biliary sepsis, pneumonia, cellulitis, and perirectal abscess), 2 presented with fever without an infectious etiology, 1 patient complained of abdominal pain, and 4 cases were found with routine blood work (1 of these patients was hospitalized with a large bowel obstruction).  8 of the 11 patients were given a repeat infusion of RTX after recovery of their neutrophil count; none went on to re-develop LON.  Bone marrow biopsies from 4 patients had the predominant cell line as lymphocytes, comprising an average of 41% (range 24-50%) of the cellular aspirate followed by monocytes (16%), promyelocytes (12%), and neutrophils/bands (8%). 

From the literature, we identified 36 patients (8 male and 28 female, average age 55) who developed LON after RTX therapy.  Again, the most common diagnosis was RA (58% of patients).  Compared to our cohort, these patients had similar times to LON, ANC nadir, and average RTX dose prior to LON.  Most patients presented asymptomatically and all survived.  Neutrophil counts recovered in all patients spontaneously or with G-CSF.  If patients received G-CSF, the only difference was time to recovery of neutrophil counts: 6.4 ± 3.2 days with G-CSF vs 11.2 ± 6.3 days without G-CSF (p=0.04).  There were no reported cases of LON recurrence when patients were given RTX after recovery of neutrophil counts.

Conclusion:  LON is a rare complication of RTX affecting approximately 5% of patients.  While these patients can present with infection, they typically recover without serious sequelae.  Among reported cases, RTX rechallenge does not lead to recurrence of neutropenia.  Though the etiology of LON is unknown, there is some evidence that LON is caused by an imbalance of lymphopoiesis and granulopoiesis and/or maturation arrest at the promyelocyte stage.


Disclosure: W. Monaco, None; W. F. C. Rigby, None; J. Jones, None.

To cite this abstract in AMA style:

Monaco W, Rigby WFC, Jones J. Rituximab Associated Late Onset Neutropenia – a Rheumatology Case Series and Review of the Literature [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/rituximab-associated-late-onset-neutropenia-a-rheumatology-case-series-and-review-of-the-literature/. Accessed .
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