A new method that selects and isolates malignant myeloma cells based on their size and molecular markers enables more precise detection of chromosomal abnormalities, University of Southern California researchers show.
The sensitivity of the approach allows physicians to classify patients based on their risk and to tailor treatment regimens, ultimately leading to better outcomes.
The study, “Microfluidic enrichment of plasma cells improves treatment of multiple myeloma,” was published in the journal Molecular Oncology.
Multiple myeloma is a cancer of plasma cells, the type of white blood cells that normally produce antibodies. The management of multiple myeloma usually is designed based on a patient’s chromosomal abnormalities. But in patients with rare plasma cells in their bone marrow, looking directly at a bone marrow biopsy sample might lead to false results.
Researchers hypothesized that enriching bone marrow samples with malignant plasma cells could improve the sensitivity and precision of myeloma diagnosis.
In early disease, plasma cells usually are positive for the CD45 surface protein, whereas CD45-negative cells are more prevalent in patients with advanced disease. This suggested that CD45-negative cells are a useful prognostic tool for categorizing myeloma risk.
Because most white blood cells are positive for the CD45 marker, researchers built the new device to deplete CD45-positive cells from bone marrow samples. Then, using specific markers for malignant plasma cells, they collected cells for chromosomal analysis.
While non-manipulated samples contained only 10.3 percent of plasma cells, the enrichment step increased this proportion to 37.7 percent.
Interestingly, the rates of chromosomal abnormalities detected were significantly different before and after the enrichment step.
Before enriching the bone marrow samples for plasma cells, 11 patients had evidence of chromosomal rearrangements. However, after that step, more than half the patients had at least one chromosomal abnormality.
“Our microfluidic method can enrich plasma cells and significantly increase the detection rates of genetic aberration in patients with multiple myeloma,” the researchers wrote.
The type of genetic abnormality usually determines the treatment regimen for myeloma patients. While Velcade (bortezomib) and Kyprolis (carfilzomib) improve the survival of patients with 14q rearrangements and 17p deletions, Revlimid (lenalidomide) delays disease progression, but does not increase survival.
So, researchers tested if their new diagnostic approach could improve the outcomes of myeloma patients. The method was tested in two myeloma patients classified as low and intermediate risk using standard methods.
After using the device, patients were reclassified as high-risk, and their treatment plans were adjusted accordingly. This led to a very good partial remission and a complete response.
“These two cases provide evidence that our microfluidic-based [method] can be used to improve diagnosis, risk stratification and management of multiple myeloma patients for better treatment outcomes,” the researchers wrote.