Rare CD138 negative plasma cell leukemia with pleomorphic morphology-CD319 to the rescue when traditional markers...

Flow cytometric identification of plasma cells can be confounded by therapeutic anti-CD38 antibodies, a phenomenon commonly encountered during measurable residual disease (MRD) assessment after chemo/immunotherapy. Less frequently, loss of plasmacell gating markers may occur due to the disease process itself. In low-resource settings, diagnostic and MRD flow cytometry panels are tailored for cost-effective use of CD markers. At baseline diagnosis, CD38, CD138, and CD45 are usually sufficient as backbone plasma-cell gating markers, and alternate markers are not routinely required.

We present a case of plasma cell leukemia in which standard diagnostic flow cytometry panels were challenged by variable CD138 expression. Given the difficulty in identifying plasma cells using conventional markers, an expanded flow cytometry panel incorporating antibody CD319 (SLAMF7) was employed.

The inclusion of CD319 enabled reliable detection of clonal plasma cells despite predominant loss of CD138 expression. This approach allowed identification of circulating malignant plasma cells outside the setting of therapeutic anti-CD38 antibody interference.

Use of alternate plasma-cell gating markers beyond the conventional backbone can be critical even in upfront diagnostic settings. Incorporating multiple, non-overlapping plasma-cell markers-including antibodies designed to avoid therapeutic masking-improves plasma-cell detection in both MRD assessment and initial diagnostic flow cytometry panels.