Morphologic and cytogenetic variables affect the flow cytometric recovery of plasma cell myeloma cells in bone marrow aspirates

Cogbill, Christopher H.; Spears, Michael D.; vanTuinen, Peter; Harrington, Alexandra M.; Olteanu, Horatiu; Kroft, Steven H.

doi:10.1111/ijlh.12411

Cited by 12 publications

(16 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Also, morphologic heterogeneity and cytogenetic heterogeneity affect the flow cytometric recovery of PCs in bone marrow aspirates of patients with MM (Cogbill et al . ), resulting in inconsistent biomarker profiles (Kim et al . ) and affecting treatment decisions (Nadav et al .…”

Section: Introductionmentioning

confidence: 99%

“…The rarity and sporadic distribution of PCs in bone marrow often leads to false-negative results when fluorescence-activated cell sorting (FACS) or cytogenetic detection is performed directly on a bone marrow biopsy sample. Also, morphologic heterogeneity and cytogenetic heterogeneity affect the flow cytometric recovery of PCs in bone marrow aspirates of patients with MM (Cogbill et al 2015), resulting in inconsistent biomarker profiles (Kim et al 2012) and affecting treatment decisions (Nadav et al 2006). Improving the sensitivity and precision of MM diagnosis could therefore significantly impact clinical outcomes.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Microfluidic enrichment of plasma cells improves treatment of multiple myeloma

et al. 2018

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Microfluidic enrichment of plasma cells improves treatment of multiple myeloma

et al. 2018

View full text Add to dashboard Cite

show abstract

“…BM biopsies are moreover costly, painful and not applicable to evaluation of extramedullary disease [16][17][18][19][20] . All of the above prevent frequent repeats and increase the likelihood of false-negative results 14,21 . Recent studies have also explored the detection of MM through peptides that detect plasma cell released exosomes but these studies have not been applied to the detection of MRD 22 .…”

Section: Introductionmentioning

confidence: 99%

Microfluidic Isolation of Aptamers with Affinity towards Multiple Myeloma Monoclonal Immunoglobulins (M-Ig)

Olsen

Tapia-Alveal

Stojanović

et al. 2020

Preprint

View full text Add to dashboard Cite

Multiple myeloma (MM) is a bone marrow cancer of resident plasma cells that affects 125,000 patients in the U.S. with ~ 30,000 new cases per year. Its signature is the clonal over-proliferation of a single plasma cell that secretes a patient specific monoclonal immunoglobulin (M-Ig). Detecting this patient specific M-Ig could allow sensitive detection of minimal residual disease in multiple myeloma from patient serum. Aptamers, single-stranded oligonucleotides with affinity and specificity to a target molecule, have recently been introduced as affinity reagents able to detect MM M-Igs. Here we adapt these benchtop M-Ig systematic evolution of ligands through exponential enrichment (SELEX) techniques to our bead integrated microfluidic SELEX (BIMS) device to rapidly generate patient specific aptamers. Using MM patient serum, we isolate patient M-Ig specific aptamers rapidly (runtime < 12 hours) with high affinity (KD < 20 nM) while consuming limited quantities of patient M-Ig (< 100 ug).

show abstract

“…(Continued to the next page) may be due to the provision of a blood-diluted sample, or a sample of liquid BM [5,6]. MFI values of β2-microglobulin were not correlated with β2-microglobulin concentrations determined by radioimmunoassay.…”

mentioning

confidence: 99%

“…Conventional 4-color, 2-tube analysis was performed using monoclonal antibodies against CD56, CD19, CD138, and CD45 for surface staining, and using kappa, and lambda monoclonal antibodies for cytoplasmic staining [3]. White blood cell counts were adjusted to 3×10 6 Fig. 2.…”

mentioning

confidence: 99%

Utility of Plasma Cell Screening Tube Kit to Differentiate Neoplastic Plasma Cells from Reactive Plasma Cells

Bang

Choi

2020

Lab Med Online

View full text Add to dashboard Cite

Flow cytometry is a powerful tool for analysis of hematologic malignancies, that provides rapid, quantitative, and multiparametric analysis of heterogeneous cell populations, but requires standardization because of complexities in panel design and interpretation. Here, we compared the Plasma Cell Screening Tube (PCST) kit (Cytognos, Spain) in conjunction with EuroFlow antibody panels for standardization of flow cytometry to a conventional method for diagnosis of plasma cell dyscrasias. Thirty-nine bone marrow samples and one peripheral blood sample from 40 patients were tested. Thirty-three patients were diagnosed with multiple myeloma (MM), and seven were in a reactive state. In PCST implementation, eight antibodies were used for staining, including anti-CD45-Pacific Blue, anti-CD19-PECy7, anti-CD138-OC515, anti-CD38-FITC, anti-CD56-PE, anti-β2microglobulin-PerCPCy5.5, anti-kappa-APC, and anti-lambda-APC-C750. Plasma cells were initially identified using CD38 and CD138; thereafter, CD38+, CD138+ gated cells were analyzed for CD56, CD19, CD45, cytoplasmic kappa, cytoplasmic lambda, and β2-microglobulin. Conventional flow cytometry was performed with six monoclonal antibodies, including anti-CD56-FITC, anti-kappa-FITC, anti-CD19-PE, anti-lambda-PE, anti-CD138-PECy5, and anti-CD45-PECy7 (Beckman Coulter, USA). Monoclonal plasma cells with cytoplasmic light-chain restriction were detected in 30 of 33 (90.9%) MM cases by conventional methods, and 32 of 33 (97.0%) MM cases with the PCST method. No differences were noted between PCST and the conventional method in immunophenotyping and plasma cell percentages (P =0.323). Among plasma cells, levels (%) were significantly higher by the PCST approach than those in the conventional method (97.6% vs 95.8%, P =0.010). PCST exhibited better performance for plasma cell dyscrasias diagnosis, and could improve laboratory efficiency and quality.

show abstract

Morphologic and cytogenetic variables affect the flow cytometric recovery of plasma cell myeloma cells in bone marrow aspirates

Abstract: Similar to prior reports, the greatest loss of PC in BM evaluation occurs between the aspirate and postlysis specimens; however, a small amount occurs from further processing. Additional morphologic and cytogenetic factors also appear to influence recovery in addition to overall PC%.

Cited by 12 publications

References 35 publications

Microfluidic enrichment of plasma cells improves treatment of multiple myeloma

Microfluidic enrichment of plasma cells improves treatment of multiple myeloma

Microfluidic Isolation of Aptamers with Affinity towards Multiple Myeloma Monoclonal Immunoglobulins (M-Ig)

Utility of Plasma Cell Screening Tube Kit to Differentiate Neoplastic Plasma Cells from Reactive Plasma Cells

Contact Info

Product

Resources

About