Rapid assessment of hyperdiploidy in plasma cell disorders using a novel multi-parametric flow cytometry method

Surbhi Sidana, Dragan Jevremovic, Rhett P. Ketterling, Nidhi Tandon, Angela Dispenzieri, Morie Gertz, Patricia T Greipp, Linda Baughn, Francis K. Buadi, Martha Lacy, William Morice, Curtis Hanson, Michael Timm, David M Dingli, Suzanne R. Hayman, Wilson Gonsalves, Prashant Kapoor, Robert A. Kyle, Nelson Leung, Ronald S. GoJohn A. Lust, S Vincent Rajkumar, Shaji K Kumar

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Trisomies of odd numbered chromosomes are seen in nearly half of patients with multiple myeloma (MM) and typically correlate with a hyperdiploid state and better overall survival (OS). We compared DNA ploidy of monoclonal plasma cells (as a surrogate for the presence of trisomies) assessed simultaneously by PCPRO (plasma cell proliferative index), a novel method that estimates DNA index by multi-parametric flow cytometry to fluorescence in situ hybridization (FISH) in 1703 patients with plasma cell disorders. The distribution of ploidy was hyperdiploid: 759 (45%), diploid 765 (45%), hypodiploid: 71 (4%), tetraploid/near-tetraploid: 108 (6%). FISH identified trisomies in 82% (621/756) of patients with hyperdiploidy by PCPRO and no trisomy by FISH was observed in 88% (730/834) of patients without hyperdiploidy. 95% (795/834) of patients without hyperdiploidy on PCPRO had one or less trisomy by FISH. Sensitivity and specificity of PCPRO for detecting hyperdiploidy was 86% (621/725) and 84% (730/865), respectively. Sensitivity increased to 94% (579/618) for patients with more than one trisomy. Newly diagnosed MM patients with hyperdiploidy on PCPRO (147/275) had better OS compared to nonhyperdiploid patients (median not reached vs 59 months, P = 0.008) and better progression free survival (median: 33 vs 23 months, P = 0.03). Within the hyperdiploidy group, patients with high-hyperdiploidy (DNA index: 1.19-1.50) versus those with low-hyperdiploidy (DNA index: 1.05-1.18) had superior OS (3 year OS of 88% vs 68% P = 0.03). Ploidy assessment by flow cytometry can provide rapid, valuable prognostic information and also reduces the number of copy number FISH probes required and hence the cost of FISH.

Original languageEnglish (US)
JournalAmerican Journal of Hematology
DOIs
StateAccepted/In press - Jan 1 2019

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Polyploidy
Plasma Cells
Flow Cytometry
Trisomy
Fluorescence In Situ Hybridization
Ploidies
Tetraploidy
Survival
DNA
Multiple Myeloma
Diploidy
Disease-Free Survival
Chromosomes
Costs and Cost Analysis
Sensitivity and Specificity

ASJC Scopus subject areas

  • Hematology

Cite this

Rapid assessment of hyperdiploidy in plasma cell disorders using a novel multi-parametric flow cytometry method. / Sidana, Surbhi; Jevremovic, Dragan; Ketterling, Rhett P.; Tandon, Nidhi; Dispenzieri, Angela; Gertz, Morie; Greipp, Patricia T; Baughn, Linda; Buadi, Francis K.; Lacy, Martha; Morice, William; Hanson, Curtis; Timm, Michael; Dingli, David M; Hayman, Suzanne R.; Gonsalves, Wilson; Kapoor, Prashant; Kyle, Robert A.; Leung, Nelson; Go, Ronald S.; Lust, John A.; Rajkumar, S Vincent; Kumar, Shaji K.

In: American Journal of Hematology, 01.01.2019.

Research output: Contribution to journalArticle

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abstract = "Trisomies of odd numbered chromosomes are seen in nearly half of patients with multiple myeloma (MM) and typically correlate with a hyperdiploid state and better overall survival (OS). We compared DNA ploidy of monoclonal plasma cells (as a surrogate for the presence of trisomies) assessed simultaneously by PCPRO (plasma cell proliferative index), a novel method that estimates DNA index by multi-parametric flow cytometry to fluorescence in situ hybridization (FISH) in 1703 patients with plasma cell disorders. The distribution of ploidy was hyperdiploid: 759 (45{\%}), diploid 765 (45{\%}), hypodiploid: 71 (4{\%}), tetraploid/near-tetraploid: 108 (6{\%}). FISH identified trisomies in 82{\%} (621/756) of patients with hyperdiploidy by PCPRO and no trisomy by FISH was observed in 88{\%} (730/834) of patients without hyperdiploidy. 95{\%} (795/834) of patients without hyperdiploidy on PCPRO had one or less trisomy by FISH. Sensitivity and specificity of PCPRO for detecting hyperdiploidy was 86{\%} (621/725) and 84{\%} (730/865), respectively. Sensitivity increased to 94{\%} (579/618) for patients with more than one trisomy. Newly diagnosed MM patients with hyperdiploidy on PCPRO (147/275) had better OS compared to nonhyperdiploid patients (median not reached vs 59 months, P = 0.008) and better progression free survival (median: 33 vs 23 months, P = 0.03). Within the hyperdiploidy group, patients with high-hyperdiploidy (DNA index: 1.19-1.50) versus those with low-hyperdiploidy (DNA index: 1.05-1.18) had superior OS (3 year OS of 88{\%} vs 68{\%} P = 0.03). Ploidy assessment by flow cytometry can provide rapid, valuable prognostic information and also reduces the number of copy number FISH probes required and hence the cost of FISH.",
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AU - Sidana, Surbhi

AU - Jevremovic, Dragan

AU - Ketterling, Rhett P.

AU - Tandon, Nidhi

AU - Dispenzieri, Angela

AU - Gertz, Morie

AU - Greipp, Patricia T

AU - Baughn, Linda

AU - Buadi, Francis K.

AU - Lacy, Martha

AU - Morice, William

AU - Hanson, Curtis

AU - Timm, Michael

AU - Dingli, David M

AU - Hayman, Suzanne R.

AU - Gonsalves, Wilson

AU - Kapoor, Prashant

AU - Kyle, Robert A.

AU - Leung, Nelson

AU - Go, Ronald S.

AU - Lust, John A.

AU - Rajkumar, S Vincent

AU - Kumar, Shaji K

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N2 - Trisomies of odd numbered chromosomes are seen in nearly half of patients with multiple myeloma (MM) and typically correlate with a hyperdiploid state and better overall survival (OS). We compared DNA ploidy of monoclonal plasma cells (as a surrogate for the presence of trisomies) assessed simultaneously by PCPRO (plasma cell proliferative index), a novel method that estimates DNA index by multi-parametric flow cytometry to fluorescence in situ hybridization (FISH) in 1703 patients with plasma cell disorders. The distribution of ploidy was hyperdiploid: 759 (45%), diploid 765 (45%), hypodiploid: 71 (4%), tetraploid/near-tetraploid: 108 (6%). FISH identified trisomies in 82% (621/756) of patients with hyperdiploidy by PCPRO and no trisomy by FISH was observed in 88% (730/834) of patients without hyperdiploidy. 95% (795/834) of patients without hyperdiploidy on PCPRO had one or less trisomy by FISH. Sensitivity and specificity of PCPRO for detecting hyperdiploidy was 86% (621/725) and 84% (730/865), respectively. Sensitivity increased to 94% (579/618) for patients with more than one trisomy. Newly diagnosed MM patients with hyperdiploidy on PCPRO (147/275) had better OS compared to nonhyperdiploid patients (median not reached vs 59 months, P = 0.008) and better progression free survival (median: 33 vs 23 months, P = 0.03). Within the hyperdiploidy group, patients with high-hyperdiploidy (DNA index: 1.19-1.50) versus those with low-hyperdiploidy (DNA index: 1.05-1.18) had superior OS (3 year OS of 88% vs 68% P = 0.03). Ploidy assessment by flow cytometry can provide rapid, valuable prognostic information and also reduces the number of copy number FISH probes required and hence the cost of FISH.

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