Multiple myeloma (MM) is a cancer of plasma cells that is associated with low blood counts, bone and calcium disorders and infections. Despite advances in treatment in the past decade, the number of deaths associated with MM has not decreased. The pros and cons of bone marrow analysis are discussed: Cytogenetics (Next Gen. Sequencing), flow cytometry and FISH. Three markers and their interactions are used to identify MM cells by flow cytometry: CD138, the gold standard for detection, CD38 and CD45. CD138 is not a reliable marker because hypoxia leads to decreased expression and missed myeloma cells. The findings for a new model that can detect a new subset of myeloma with significant clonality using CD38 as a more specific marker for cell types other than MM cells are discussed. The definition and assessment of Minimal Residual Disease has changed the way we view therapeutic response in MM, and, with refinement, it can be a force to reform classifications, alter management paradigms, and identify those patients who may yet achieve a functional cure. There is no known way to detect circulating myeloma cells due to hypoxia. However, the new model is promising as it detected >80% of circulating cells, suggesting detecting myeloma without biopsies is possible using the right markers.
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