CD138 Enrichment Strategy and Results of Chromosome Genomic Array Testing (CGAT) for Multiple Myelomas

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.