Detection of clonal plasma cells in POEMS syndrome using multiparameter flow cytometry

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Abstract

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein [M-protein], and skin changes) is a rare systemic disorder characterized by various symptoms caused by underlying plasma cell (PC) dyscrasia. Detection of monoclonal PCs is mandatory for the diagnosis of POEMS syndrome; however, the usefulness of EuroFlow-based next-generation flow cytometry (EuroFlow-NGF) in POEMS syndrome for detecting monoclonal PCs in bone marrow (BM) and the gating strategy suitable for flow cytometry study of POEMS syndrome remain unknown. We employed EuroFlow-NGF-based single-tube eight-color multiparameter flow cytometry (MM-flow) and established a new gating strategy (POEMS-flow) to detect the monoclonal PCs in POEMS syndrome, gating CD38 broadly from dim to bright and CD45 narrowly from negative to dim compared to MM-flow. MM-flow detected monoclonal PCs in 9/25 (36.0%) cases, including 2/2 immunofixation electrophoresis (IFE)-negative cases (100%). However, POEMS-flow detected monoclonal PCs in 18/25 cases (72.0%), including 2/2 IFE-negative cases (100%). POEMS-flow detected monoclonal PCs with immunophenotypes of CD19 ⁻ in 17/18 (94.4%). In six cases where post-treatment samples were available, the size of the clones was significantly reduced after the treatment ( P = 0.031). POEMS-flow can enhance the identification rate of monoclonal PCs in POEMS syndrome and become a valuable tool for the diagnosis of POEMS syndrome.

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International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma.

Shaji Kumar, Bruno Paiva, Kenneth Anderson … (2016)

Treatment of multiple myeloma has substantially changed over the past decade with the introduction of several classes of new effective drugs that have greatly improved the rates and depth of response. Response criteria in multiple myeloma were developed to use serum and urine assessment of monoclonal proteins and bone marrow assessment (which is relatively insensitive). Given the high rates of complete response seen in patients with multiple myeloma with new treatment approaches, new response categories need to be defined that can identify responses that are deeper than those conventionally defined as complete response. Recent attempts have focused on the identification of residual tumour cells in the bone marrow using flow cytometry or gene sequencing. Furthermore, sensitive imaging techniques can be used to detect the presence of residual disease outside of the bone marrow. Combining these new methods, the International Myeloma Working Group has defined new response categories of minimal residual disease negativity, with or without imaging-based absence of extramedullary disease, to allow uniform reporting within and outside clinical trials. In this Review, we clarify several aspects of disease response assessment, along with endpoints for clinical trials, and highlight future directions for disease response assessments.

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Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma

J Flores-Montero, L Sanoja-Flores, B. Paiva … (2017)

Flow cytometry has become a highly valuable method to monitor minimal residual disease (MRD) and evaluate the depth of complete response (CR) in bone marrow (BM) of multiple myeloma (MM) after therapy. However, current flow-MRD has lower sensitivity than molecular methods and lacks standardization. Here we report on a novel next generation flow (NGF) approach for highly sensitive and standardized MRD detection in MM. An optimized 2-tube 8-color antibody panel was constructed in five cycles of design-evaluation-redesign. In addition, a bulk-lysis procedure was established for acquisition of ⩾107 cells/sample, and novel software tools were constructed for automatic plasma cell gating. Multicenter evaluation of 110 follow-up BM from MM patients in very good partial response (VGPR) or CR showed a higher sensitivity for NGF-MRD vs conventional 8-color flow-MRD -MRD-positive rate of 47 vs 34% (P=0.003)-. Thus, 25% of patients classified as MRD-negative by conventional 8-color flow were MRD-positive by NGF, translating into a significantly longer progression-free survival for MRD-negative vs MRD-positive CR patients by NGF (75% progression-free survival not reached vs 7 months; P=0.02). This study establishes EuroFlow-based NGF as a highly sensitive, fully standardized approach for MRD detection in MM which overcomes the major limitations of conventional flow-MRD methods and is ready for implementation in routine diagnostics.

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POEMS syndrome: definitions and long-term outcome.

P Greipp, Rita Basu, S Rajkumar … (2003)

The POEMS syndrome (coined to refer to polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) remains poorly understood. Ambiguity exists over the features necessary to establish the diagnosis, treatment efficacy, and prognosis. We identified 99 patients with POEMS syndrome. Minimal criteria were a sensorimotor peripheral neuropathy and evidence of a monoclonal plasmaproliferative disorder. To distinguish POEMS from neuropathy associated with monoclonal gammopathy of undetermined significance, additional criteria were included: a bone lesion, Castleman disease, organomegaly (or lymphadenopathy), endocrinopathy, edema (peripheral edema, ascites, or effusions), and skin changes. The median age at presentation was 51 years; 63% were men. Median survival was 165 months. With the exception of fingernail clubbing (P =.03) and extravascular volume overload (P =.04), no presenting feature, including the number of presenting features, was predictive of survival. Response to therapy (P <.001) was predictive of survival. Pulmonary hypertension, renal failure, thrombotic events, and congestive heart failure were observed and appear to be part of the syndrome. In 18 patients (18%), new disease manifestations developed over time. More than 50% of patients had a response to radiation, and 22% to 50% had responses to prednisone and a combination of melphalan and prednisone, respectively. We conclude that the median survival of patients with POEMS syndrome is 165 months, independent of the number of syndrome features, bone lesions, or plasma cells at diagnosis. Additional features of the syndrome often develop, but the complications of classic multiple myeloma rarely develop.

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Author and article information

Contributors

Shokichi Tsukamoto: shokichi.tsukamoto@chiba-u.jp

Journal

Journal ID (nlm-ta): Sci Rep

Journal ID (iso-abbrev): Sci Rep

Title: Scientific Reports

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2045-2322

Publication date (Electronic): 6 May 2024

Publication date PMC-release: 6 May 2024

Publication date Collection: 2024

Volume: 14

Electronic Location Identifier: 10362

Affiliations

[1 ]Department of Hematology, Chiba University Hospital, ( https://ror.org/0126xah18) Chiba, Japan

[2 ]Department of Endocrinology, Hematology, and Gerontology, Chiba University Graduate School of Medicine, ( https://ror.org/01hjzeq58) Chiba, Japan

[3 ]Department of Transfusion Medicine and Cell Therapy, Chiba University Hospital, ( https://ror.org/0126xah18) Chiba, Japan

[4 ]Department of Neurology, Chiba University Graduate School of Medicine, ( https://ror.org/01hjzeq58) Chiba, Japan

[5 ]Department of Hematology, International University of Health and Welfare, ( https://ror.org/053d3tv41) Narita, Japan

[6 ]Department of Hematology, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University, ( https://ror.org/02hwp6a56) Kanazawa, Japan

Article

Publisher ID: 61034

DOI: 10.1038/s41598-024-61034-1

PMC ID: 11074311

PubMed ID: 38710832

SO-VID: 5fe83dbe-bcaf-4410-8482-418defd33017

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Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 6 April 2023

Date accepted : 30 April 2024

Funding

Funded by: Research funding and consulting fees from SRL, Inc.

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ScienceOpen disciplines: Uncategorized

Keywords: poems syndrome,multiparameter flow cytometry,euroflow,immunophenotype,flow cytometry,myeloma

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ScienceOpen disciplines: Uncategorized

Keywords: poems syndrome, multiparameter flow cytometry, euroflow, immunophenotype, flow cytometry, myeloma

Detection of clonal plasma cells in POEMS syndrome using multiparameter flow cytometry

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Most cited references 25

International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma.

Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma

POEMS syndrome: definitions and long-term outcome.

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