Background: CD138 enrichment of multiple myeloma (MM) samples significantly improves the FISH
detection rate. In a pilot study of 46 patients, we previously showed CD138 enrichment
with abnormal plasma cells by flow between 0.5% ~ 40% dramatically improved detection
rate by CGAT: 85% abnormal by CGAT and 89% abnormal by FISH with 80% concordance.
CGAT found additional markers in 83% of the samples, 6.5% of which were not detected
by FISH. In 15% of the cases, FISH uniquely detected low-level abnormalities. Methods: Based on these findings, the MM Pathway testing scheme was implemented. CD138+enrichment
was performed on samples with 0.01% ~ 0.5% plasma cells for FISH only, on samples
with >0.5% ~ 6% plasma cells for both FISH and CGAT, and >6% ~ 40% for CGAT only.
Since implementation, 306 total MM samples were tested. We compared results from 130
of the samples with concurrent karyotype, FISH and CGAT. Results: Overall detection rate was 99.2%, with abnormal karyotype in 40%, abnormal CGAT in
93%, and abnormal FISH in 98.5%. Concordance between FISH and CGAT for high-risk imbalances
was consistently >90%. Besides common MM abnormalities, CGAT found frequent losses
of X, 6q, 14q, and 16q and cnLOH of chromosomes 1, 4, 12, 14, and 16q. A strong association
of 14q cnLOH with t(11;14) was observed, and chromosome 4 abnormalities often concur
with 16q aberrations, half of which were cnLOH. Conclusions: CD138 enrichment is important for MM testing. Our Pathway testing scheme with judicious
use of CGAT and FISH based on plasma cell content offers maximum diagnostic yield.
To read this article in full you will need to make a payment