Abstract
Cytogenetic alterations form the basis for risk stratification for multiple myeloma (MM) and guide the selection of therapy; however, current pathology assays performed on bone marrow samples can produce false‐negatives due to the unpredictable distribution and rarity of MM cells. Here, we report on a microfluidic device used to facilitate CD45 depletion to enhance the detection of cytogenetic alterations in plasma cells (PCs). Bone marrow samples from 48 patients with MM were each divided into two aliquots. One aliquot was subjected to classic flow cytometry and fluorescent in situ hybridization (FISH). The other first went through CD45+ cell depletion, further enriched by microfluidic size selection. The enriched samples were then analyzed using flow cytometry and FISH and compared to those analyzed using the classic method only. Unlike the traditional method, the microfluidic device removed the CD45+ leukocytes and specifically selected PCs from the remaining white blood cells. Therefore, the microfluidic method (MF‐CD45‐TACs) significantly increased the percentage of CD38+/CD138+ cells to 37.7 ± 20.4% (P < 0.001) from 10.3 ± 8.5% in bone marrow. After the MF‐CD45‐TAC enrichment, the detection rate of IgH rearrangement, del(13q14), del(17p), and 1q21 gains, rose to 56.3% (P < 0.001), 37.5% (P < 0.001), 22.9% (P < 0.001), and 41.7% (P = 0.001), respectively; all rates of detection were significantly increased compared to the classically analyzed samples. In this clinical trial, this microfluidic‐assisted assay provided a precise detection of cytogenetic alterations in PCs and improved clinical outcomes.
Highlights
Multiple myeloma (MM) is an incurable neoplasm of plasma cells (PCs) that affects more than 20 000 people annually in the United States
As an improvement over traditional methods, we developed a microfluidic method to enrich PCs for flow cytometry and fluorescent in situ hybridization (FISH) assays (Fig. 1)
tetrameric antibody complexes (TACs)) significantly increased the percentage of CD38+/CD138+ cells to 37.7 Æ 20.4% (P < 0.001) from 10.3 Æ 8.5% in unmanipulated bone marrow (Table 1)
Summary
Multiple myeloma (MM) is an incurable neoplasm of plasma cells (PCs) that affects more than 20 000 people annually in the United States. Thalidomide, lenalidomide, and Abbreviations AJH, American Journal of Hematology; DLD, deterministic lateral displacement; FACS, fluorescence-activated cell sorting; FISH, fluorescent in situ hybridization; IMWG, International Myeloma Working Group; MACS, magnetic-activated cell sorting; MF-CD45-TACs, microfluidic– CD45 depletion–tetrameric antibody complexes; MM, multiple myeloma; PCs, plasma cells; PDMS, polydimethylsiloxane; TACs, tetrameric antibody complexes; VRD, bortezomib, lenalidomide, and dexamethasone; VTD, bortezomib, thalidomide, and dexamethasone.
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