B-cell repopulation is temporally associated with relapses in NMOSD.

CD27⁺ memory B-cell monitoring may better predict relapse risk than CD19⁺ alone.

Fixed rituximab dosing may lead to overtreatment or insufficient disease control.

Relapses can occur even without B-cell repopulation, suggesting other mechanisms.

Standardized protocols and personalized retreatment based on flow cytometry may improve clinical outcomes.

To evaluate the utility of peripheral blood B-cell counts, specifically CD19+ and CD27+ lymphocytes by flow cytometry, in patients with neuromyelitis optica (NMO) treated with rituximab.

A systematic review was conducted following the PRISMA guidelines. Searches were performed in PubMed, LILACS, Cochrane, and ClinicalTrials databases up to July 2024, including studies in English, Spanish, and French. Studies were selected based on predefined eligibility criteria, and data extraction was performed independently by two reviewer teams. Risk of bias was assessed using the JBI Critical Appraisal Tool, and the certainty of evidence was evaluated with the GRADE methodology.

A total of 3325 studies were identified, of which 22 met the inclusion criteria, analyzing 633 patients. Most studies used rituximab induction schemes of 375 mg/m² weekly (46%) or 1 g biweekly (38%). Retreatment protocols varied widely, and 84.6% of studies measured CD19+ cells, while 42.3 % also included CD27+ memory B cells. The most common depletion thresholds were <1% for CD19+ and <0.05% for CD27+. Repopulation occurred between 2.5 and 12.72 months, with 26% peaking at 6 months. Recurrent disease was reported in 200 patients (31.5%), with 64.5% of relapses associated with B-cell repopulation. However, 35% of relapses occurred without B-cell return. The quality of evidence was limited due to methodological heterogeneity, small sample sizes, and variability in monitoring protocols.

B-cell repopulation appears to be temporally associated with relapses in NMO, highlighting the potential value of CD19+ and CD27+ monitoring by flow cytometry to guide retreatment strategies. However, relapses also occurred in the absence of repopulation, suggesting other pathophysiological mechanisms. There is a pressing need for standardized treatment protocols and prospective, multicenter studies to define the optimal use of B-cell monitoring in clinical practice.

B-cell monitoring

CD19+ lymphocytes

CD27+ memory B cells

Flow cytometry

Neuromyelitis optica

Relapse

Rituximab

Systematic review

© 2025 The Authors. Published by Elsevier B.V.