Ten Color Multiparameter Flow Cytometry in Bone Marrow and Apheresis Products for Assessment and Outcome Prediction in Multiple Myeloma Patients

ObjectiveIn clinical trials (CTs), the assessment of minimal residual disease (MRD) has proven to have prognostic value for multiple myeloma (MM) patients. Multiparameter flow cytometry (MFC) and next-generation sequencing are currently used in CTs as effective tools for outcome prediction. We have...

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Main Authors: Veronika Riebl, Sandra Maria Dold, Dagmar Wider, Marie Follo, Gabriele Ihorst, Johannes M. Waldschmidt, Johannes Jung, Michael Rassner, Christine Greil, Ralph Wäsch, Monika Engelhardt
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-08-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2021.708231/full
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author Veronika Riebl
Sandra Maria Dold
Sandra Maria Dold
Dagmar Wider
Marie Follo
Gabriele Ihorst
Johannes M. Waldschmidt
Johannes Jung
Michael Rassner
Michael Rassner
Christine Greil
Ralph Wäsch
Ralph Wäsch
Monika Engelhardt
Monika Engelhardt
author_facet Veronika Riebl
Sandra Maria Dold
Sandra Maria Dold
Dagmar Wider
Marie Follo
Gabriele Ihorst
Johannes M. Waldschmidt
Johannes Jung
Michael Rassner
Michael Rassner
Christine Greil
Ralph Wäsch
Ralph Wäsch
Monika Engelhardt
Monika Engelhardt
author_sort Veronika Riebl
collection DOAJ
description ObjectiveIn clinical trials (CTs), the assessment of minimal residual disease (MRD) has proven to have prognostic value for multiple myeloma (MM) patients. Multiparameter flow cytometry (MFC) and next-generation sequencing are currently used in CTs as effective tools for outcome prediction. We have previously described 6- and 8-color MFC panels with and without kappa/lambda, which were equally reliable in detecting aberrant plasma cells (aPC) in myeloma bone marrow (BM) specimens. This follow-up study a) established a highly sensitive single-tube 10-color MFC panel for MRD detection in myeloma samples carrying different disease burden (monoclonal gammopathy of unknown significance (MGUS), smoldering multiple myeloma (SMM), MM), b) evaluated additional, rarely used markers included in this panel, and c) assessed MRD levels and the predictive value in apheresis vs. BM samples of MM patients undergoing autologous stem cell transplantation (ASCT).Methods + ResultsThe 10-color MFC was performed in BM and apheresis samples of 128 MM and pre-MM (MGUS/SMM) patients. The markers CD28, CD200, CD19, and CD117 underwent closer examination. The analysis revealed distinct differences in these antigens between MM, MGUS/SMM, and patients under treatment. In apheresis samples, the 10-color panel determined MRD negativity in 44% of patients. Absence of aPC in apheresis corresponded with disease burden, cytogenetics, and response to induction. It also determined MRD negativity in BM samples after ASCT and was associated with improved progression-free survival.ConclusionThese results highlight the significance of the evaluation of both BM and apheresis samples with a novel highly sensitive 10-color MFC panel.
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spelling doaj.art-22ba87e8d4604950ad5bceae64330e702022-12-21T22:20:44ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-08-011110.3389/fonc.2021.708231708231Ten Color Multiparameter Flow Cytometry in Bone Marrow and Apheresis Products for Assessment and Outcome Prediction in Multiple Myeloma PatientsVeronika Riebl0Sandra Maria Dold1Sandra Maria Dold2Dagmar Wider3Marie Follo4Gabriele Ihorst5Johannes M. Waldschmidt6Johannes Jung7Michael Rassner8Michael Rassner9Christine Greil10Ralph Wäsch11Ralph Wäsch12Monika Engelhardt13Monika Engelhardt14Department of Medicine I Hematology and Oncology, Faculty of Medicine, Medical Center – University of Freiburg, Freiburg, GermanyDepartment of Medicine I Hematology and Oncology, Faculty of Medicine, Medical Center – University of Freiburg, Freiburg, GermanyFaculty of Biology, University of Freiburg, Freiburg, GermanyDepartment of Medicine I Hematology and Oncology, Faculty of Medicine, Medical Center – University of Freiburg, Freiburg, GermanyDepartment of Medicine I Hematology and Oncology, Faculty of Medicine, Medical Center – University of Freiburg, Freiburg, GermanyClinical Trials Unit, Faculty of Medicine, Medical Center – University of Freiburg, Freiburg, GermanyDepartment of Medicine I Hematology and Oncology, Faculty of Medicine, Medical Center – University of Freiburg, Freiburg, GermanyDepartment of Medicine I Hematology and Oncology, Faculty of Medicine, Medical Center – University of Freiburg, Freiburg, GermanyDepartment of Medicine I Hematology and Oncology, Faculty of Medicine, Medical Center – University of Freiburg, Freiburg, GermanyComprehensive Cancer Center Freiburg (CCCF), Faculty of Medicine, Medical Center – University of Freiburg, Freiburg, GermanyDepartment of Medicine I Hematology and Oncology, Faculty of Medicine, Medical Center – University of Freiburg, Freiburg, GermanyDepartment of Medicine I Hematology and Oncology, Faculty of Medicine, Medical Center – University of Freiburg, Freiburg, GermanyComprehensive Cancer Center Freiburg (CCCF), Faculty of Medicine, Medical Center – University of Freiburg, Freiburg, GermanyDepartment of Medicine I Hematology and Oncology, Faculty of Medicine, Medical Center – University of Freiburg, Freiburg, GermanyComprehensive Cancer Center Freiburg (CCCF), Faculty of Medicine, Medical Center – University of Freiburg, Freiburg, GermanyObjectiveIn clinical trials (CTs), the assessment of minimal residual disease (MRD) has proven to have prognostic value for multiple myeloma (MM) patients. Multiparameter flow cytometry (MFC) and next-generation sequencing are currently used in CTs as effective tools for outcome prediction. We have previously described 6- and 8-color MFC panels with and without kappa/lambda, which were equally reliable in detecting aberrant plasma cells (aPC) in myeloma bone marrow (BM) specimens. This follow-up study a) established a highly sensitive single-tube 10-color MFC panel for MRD detection in myeloma samples carrying different disease burden (monoclonal gammopathy of unknown significance (MGUS), smoldering multiple myeloma (SMM), MM), b) evaluated additional, rarely used markers included in this panel, and c) assessed MRD levels and the predictive value in apheresis vs. BM samples of MM patients undergoing autologous stem cell transplantation (ASCT).Methods + ResultsThe 10-color MFC was performed in BM and apheresis samples of 128 MM and pre-MM (MGUS/SMM) patients. The markers CD28, CD200, CD19, and CD117 underwent closer examination. The analysis revealed distinct differences in these antigens between MM, MGUS/SMM, and patients under treatment. In apheresis samples, the 10-color panel determined MRD negativity in 44% of patients. Absence of aPC in apheresis corresponded with disease burden, cytogenetics, and response to induction. It also determined MRD negativity in BM samples after ASCT and was associated with improved progression-free survival.ConclusionThese results highlight the significance of the evaluation of both BM and apheresis samples with a novel highly sensitive 10-color MFC panel.https://www.frontiersin.org/articles/10.3389/fonc.2021.708231/fullminimal residual diseasemultiple myelomamultiparameter flow cytometryimproved progression-free survivalphenotypic analysesbone marrow
spellingShingle Veronika Riebl
Sandra Maria Dold
Sandra Maria Dold
Dagmar Wider
Marie Follo
Gabriele Ihorst
Johannes M. Waldschmidt
Johannes Jung
Michael Rassner
Michael Rassner
Christine Greil
Ralph Wäsch
Ralph Wäsch
Monika Engelhardt
Monika Engelhardt
Ten Color Multiparameter Flow Cytometry in Bone Marrow and Apheresis Products for Assessment and Outcome Prediction in Multiple Myeloma Patients
Frontiers in Oncology
minimal residual disease
multiple myeloma
multiparameter flow cytometry
improved progression-free survival
phenotypic analyses
bone marrow
title Ten Color Multiparameter Flow Cytometry in Bone Marrow and Apheresis Products for Assessment and Outcome Prediction in Multiple Myeloma Patients
title_full Ten Color Multiparameter Flow Cytometry in Bone Marrow and Apheresis Products for Assessment and Outcome Prediction in Multiple Myeloma Patients
title_fullStr Ten Color Multiparameter Flow Cytometry in Bone Marrow and Apheresis Products for Assessment and Outcome Prediction in Multiple Myeloma Patients
title_full_unstemmed Ten Color Multiparameter Flow Cytometry in Bone Marrow and Apheresis Products for Assessment and Outcome Prediction in Multiple Myeloma Patients
title_short Ten Color Multiparameter Flow Cytometry in Bone Marrow and Apheresis Products for Assessment and Outcome Prediction in Multiple Myeloma Patients
title_sort ten color multiparameter flow cytometry in bone marrow and apheresis products for assessment and outcome prediction in multiple myeloma patients
topic minimal residual disease
multiple myeloma
multiparameter flow cytometry
improved progression-free survival
phenotypic analyses
bone marrow
url https://www.frontiersin.org/articles/10.3389/fonc.2021.708231/full
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