scholarly journals Multiparameter Flow Cytometry for the Identification of Neoplastic Plasma Cells in POEMS Syndrome with IgG-kappa Gammopathy: Successful Treatment Using Lenalidomide and Dexamethasone

2019 ◽  
Vol 58 (23) ◽  
pp. 3461-3468
Author(s):  
Sho Ikeda ◽  
Takahiro Kobayashi ◽  
Masaya Saito ◽  
Atsushi Komatsuda ◽  
Kumi Ubukawa ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Successful Treatment ◽  
Plasma Cells ◽  
Poems Syndrome ◽  
Multiparameter Flow Cytometry

Defining Complete Response in Multiple Myeloma: Role of the Serum Free Light Chain Assay and Multiparameter Flow Cytometry.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1479-1479 ◽  
Author(s):  
Roger G. Owen ◽  
J. Anthony Child ◽  
Andy C. Rawstron ◽  
Sue Bell ◽  
Kim Cocks ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Light Chain ◽  
Plasma Cells ◽  
Complete Response ◽  
Free Light Chain ◽  
Multiparameter Flow Cytometry ◽  
High Dose ◽  
Reference Laboratory ◽  
Serum Free ◽  
Serum Free Light Chain

Abstract It is becoming increasingly clear that the use of immunofixation (IF) to define complete response (CR) in MM has its limitations. Paraprotein concentration is not a direct measure of tumour bulk and maximal responses may take many months to achieve which inevitably underestimate CR rates in therapeutic schedules that contain the sequential use of different agents. The purpose of this study was to prospectively assess the applicability and value of the serum free light chain (SFLC) assay and multiparameter flow cytometry (MFC) to assess CR in the intensive pathway of the MRC Myeloma IX Trial. In this trial patients are initially randomised to induction with CVAD or CTD and patients with stable disease or better proceed to high dose melphalan (HDM) with stem cell support. There is a second randomisation to maintenance thalidomide or no further therapy. SFLC as well as standard serum and urine paraprotein assessments were performed in a central reference laboratory at the following time points: presentation, end of induction, day 100 post HDM and 3 monthly until relapse. Similarly MFC in which neoplastic plasma cells are identified and differentiated from normal plasma cells on the basis of CD19 and CD56 expression was evaluated (again in a central laboratory) at presentation, end of induction and day 100 following HDM and annually until relapse. An initial analysis of 207/1114 randomised patients was performed and the results are detailed below - End of induction Day 100 post HDM IF negative 16.3% 49.4% SFLC normal 46.1% 78.6% MFC negative 10.2% 50.7% The SFLC assay was informative in 95% of patients and provided for a more rapid assessment of response than conventional methods. A normal SFLC assay at the end of induction appeared to predict for attainment of an IF-neg CR at day 100 (70% IF-neg CR if SFLC normal vs 30% when SFLC abnormal at the end of induction). It should however be noted that 58% of patients who failed to achieve an IF-neg CR at day 100 had a normal SFLC assay. MFC provides for a direct assessment of residual neoplastic plasma cells. The assay was informative in 96.7% of patients and has a reproducible sensitivity of 0.01%. The majority of patients (89.8%) had detectable disease at the end of induction with a median of 0.7% neoplastic plasma cells (range 0.01–14%). Further cytoreduction was provided by the HDM such that 49.3% had flow detectable disease at day 100 with a median of 0.26% neoplastic plasma cells (range 0.02–8%). 30% of patients with IF-neg CR had detectable disease while 21% of patients with a persistent paraprotein had no detectable disease in their marrow. The majority of the latter patients had IgG paraproteins and it is postulated that many of these pts will ultimately achieve an IF-neg CR. We would conclude that given the kinetics of paraprotein clearance in MM it may be more appropriate to define CR on the basis of a normal SFLC assay and the absence of minimal residual disease by MFC. In this way it should be possible to more accurately define the CR rate achieved by individual components of multi-agent sequential regimens.

The persistence of immunophenotypically normal residual bone marrow plasma cells at diagnosis identifies a good prognostic subgroup of symptomatic multiple myeloma patients

Blood ◽  
2009 ◽  
Vol 114 (20) ◽  
pp. 4369-4372 ◽  
Author(s):  
Bruno Paiva ◽  
Maria-Belén Vidriales ◽  
Gema Mateo ◽  
Jose J. Pérez ◽  
Maria Angeles Montalbán ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Plasma Cells ◽  
Progression Free Survival ◽  
Multiparameter Flow Cytometry ◽  
Therapeutic Approaches ◽  
Clinical Value ◽  
Cell Compartment ◽  
Free Survival ◽  
Bone Marrow Plasma

Abstract Multiparameter flow cytometry immunophenotyping allows discrimination between normal (N-) and myelomatous (MM-) plasma cells (PCs) within the bone marrow plasma cell compartment (BMPCs). Here we report on the prognostic relevance of detecting more than 5% residual normal plasma cells from all bone marrow plasma cells (N-PCs/BMPCs) by multiparameter flow cytometry in a series of 594 newly diagnosed symptomatic MM patients, uniformly treated according to the Grupo Español de MM 2000 (GEM2000) protocol. Our results show that symptomatic MM patients with more than 5% N-PCs/BMPCs (n = 80 of 594; 14%) have a favorable baseline clinical prospect, together with a significantly lower frequency of high-risk cytogenetic abnormalities and higher response rates. Moreover, this group of patients had a significantly longer progression-free survival (median, 54 vs 42 months, P = .001) and overall survival (median, not reached vs 89 months, P = .04) than patients with less than or equal to 5% N-PCs/BMPCs. Our findings support the clinical value of detecting residual normal PCs in MM patients at diagnosis because this reveals a good prognostic category that could benefit from specific therapeutic approaches. This trial was registered at www.clinicaltrials.gov as NCT00560053.

scholarly journals Comparison of minimal residual disease detection in multiple myeloma between the DuraClone and EuroFlow methods

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takeshi Yoroidaka ◽  
Kentaro Narita ◽  
Hiroyuki Takamatsu ◽  
Momoko Fujisawa ◽  
Shinji Nakao ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Flow Cytometry ◽  
Minimal Residual Disease ◽  
Plasma Cells ◽  
Residual Disease ◽  
Total Cell ◽  
Multiparameter Flow Cytometry ◽  
Single Tube ◽  
The Cost ◽  
Minimal Residual

AbstractIn this study, the minimal residual disease (MRD) levels in patients with multiple myeloma (MM) were assessed by comparing the new 8-color single-tube multiparameter flow cytometry method (DuraClone), which reduces the cost of antibodies and labor burden of laboratories, with the EuroFlow next-generation flow (NGF) method. A total of 96 samples derived from 69 patients with MM were assessed to determine the total cell acquisition number (tCAN), percentages of total and normal plasma cells (PCs), and MRD levels using two methods. We found that the tCAN was significantly higher with EuroFlow-NGF than with DuraClone (median 8.6 × 106 vs. 5.7 × 106; p < 0.0001). In addition, a significant correlation in the MRD levels between the two methods was noted (r = 0.92, p < 0.0001). However, in the qualitative analysis, 5.2% (5/96) of the samples showed discrepancies in the MRD levels. In conclusion, the DuraClone is a good option to evaluate MRD in multiple myeloma but it should be used with caution.

Utility of 8-colours multiparameter flow cytometry immunophenotyping of plasma cells for the management of monoclonal gammopathy

2013 ◽  
Vol 71 (3) ◽  
pp. 313-323
Author(s):  
Mélanie Gressier ◽  
Michael Chaquin ◽  
Ludovic Lhermitte ◽  
Vahid Asnafi ◽  
Elizabeth Macintyre ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Multiparameter Flow Cytometry

Multiparameter Flow Cytometry Remission Is the Most Relevant Prognostic Factor for Multiple Myeloma Patients Who Undergo Autologous Stem Cell Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 737-737
Author(s):  
Bruno Paiva ◽  
Maria-Belén Vidriales ◽  
Jorge Cerveró ◽  
Gema Mateo ◽  
Jose J. Pérez ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Flow Cytometry ◽  
Stem Cell ◽  
Plasma Cells ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Patient Specific ◽  
Multiparameter Flow Cytometry ◽  
Cell Transplant ◽  
Post Transplant

Abstract Minimal residual disease (MRD) assessment is standard in many hematologic malignancies but is considered investigational in multiple myeloma (MM). We report a prospective analysis of the prognostic importance of MRD detection by multiparameter flow cytometry (MFC) in 295 newly diagnosed MM patients uniformly treated in the GEM2000 protocol (VBMCP/VBAD induction plus autologous stem cell transplant [ASCT]). MRD status by MFC was determined at day 100 post-ASCT. Persistent myelomatous plasma cells (MM-PCs) were detected by MFC in 170 patients (58%), who were considered MRD-positive. Progression-free survival (PFS; median 71 vs 37 months, P < .0001) and overall survival (OS; median not reached vs 89 months, P = .002) were longer in patients who were MRD-negative versus MRD-positive at day 100 post-ASCT, with a 5-year PFS rate of 60% and 22% (P < .0001), respectively. Similar prognostic differentiation was seen in 147 patients who achieved immunofixation (IFx) negative complete response post-ASCT. The 5-year PFS rate was 62% in MRD-negative patients (n=94) versus 30% in MRD-positive patients (n=53; P < .0001), and the respective 5-year OS rates were 87% versus 59% (P = .009). Moreover, MRD− IFx− and MRD− IFx+ patients had significantly longer PFS than MRD+ IFx− patients (median 71, 65, and 37 months, respectively, P = .0002). By multivariate analysis, only MRD status by MFC at day 100 post-ASCT and FISH cytogenetics were identified as independent prognostic factors for PFS, and only MRD status by MFC and age were identified for OS. The relative risks of progression and death among MRD-positive versus MRD-negative patients were 3.64 (P = .002) and 2.02 (P = .02), respectively. Finally, a subgroup of 157 patients in which MRD information was available both pre- and post-ASCT were analyzed. Patients who were MRD-positive both pre- and post-transplant (n=93) had the worst prognosis; patients who were MRD-positive pre-ASCT but improved to MRD-negative post-ASCT (n=48) had an intermediate prognosis, and patients who were MRD-negative both pre- and post-transplant (n=16) had the best prognosis. The 5-year PFS and OS rates in these three prognostic subgroups were 25%, 57%, and 80%, respectively (P = .0001), and 59%, 78%, and 100%, respectively (P = .06). In summary, our results show that MRD evaluation by MFC is a very useful technique to identify patients at different risk of progression. This type of analysis, particularly when performed post-ASCT, may contribute to the design of patient-specific maintenance treatment approaches, as well as the evaluation of the potential benefits of consolidation therapies.

scholarly journals Correlation of multiparameter flow cytometry and bone marrow trephine immunohistochemistry in the identification and characterization of neoplastic plasma cells

2016 ◽  
Vol 179 (3) ◽  
pp. 499-501 ◽  
Author(s):  
Thomas Menter ◽  
Abbas H. Abdulsalam ◽  
Elisabet Nadal-Melsio ◽  
Eva Yebra-Fernandez ◽  
Rashpal S. Flora ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Plasma Cells ◽  
Multiparameter Flow Cytometry ◽  
Bone Marrow Trephine ◽  
Identification And Characterization

New criteria to identify risk of progression in monoclonal gammopathy of uncertain significance and smoldering multiple myeloma based on multiparameter flow cytometry analysis of bone marrow plasma cells

Blood ◽  
2007 ◽  
Vol 110 (7) ◽  
pp. 2586-2592 ◽  
Author(s):  
Ernesto Pérez-Persona ◽  
María-Belén Vidriales ◽  
Gema Mateo ◽  
Ramón García-Sanz ◽  
Maria-Victoria Mateos ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Flow Cytometry ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Progression Free Survival ◽  
Multiparameter Flow Cytometry ◽  
Smoldering Multiple Myeloma ◽  
Uncertain Significance ◽  
Risk Of Progression

Monoclonal gammopathy of uncertain significance (MGUS) and smoldering multiple myeloma (SMM) are plasma cell disorders with a risk of progression of approximately 1% and 10% per year, respectively. We have previously shown that the proportion of bone marrow (BM) aberrant plasma cells (aPCs) within the BMPC compartment (aPC/BMPC) as assessed by flow cytometry (FC) contributes to differential diagnosis between MGUS and multiple myloma (MM). The goal of the present study was to investigate this parameter as a marker for risk of progression in MGUS (n = 407) and SMM (n = 93). Patients with a marked predominance of aPCs/BMPC (≥ 95%) at diagnosis displayed a significantly higher risk of progression both in MGUS and SMM (P< .001). Multivariate analysis for progression-free survival (PFS) selected the percentage aPC/BMPC (≥ 95%) as the most important independent variable, together with DNA aneuploidy and immunoparesis, for MGUS and SMM, respectively. Using these independent variables, we have identified 3 risk categories in MGUS (PFS at 5 years of 2%, 10%, and 46%, respectively; P< .001) and SMM patients (PFS at 5 years of 4%, 46%, and 72%, respectively; P < .001). Our results show that multiparameter FC evaluation of BMPC at diagnosis is a valuable tool that could help to individualize the follow-up strategy for MGUS and SMM patients.

scholarly journals Detection of Clonal Plasma Cells in POEMS Syndrome Using Multiparameter Flow Cytometry

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2697-2697
Author(s):  
Arata Ishii ◽  
Shokichi Tsukamoto ◽  
Naoya Mimura ◽  
Yurie Nagai ◽  
Shinichiro Matsui ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Research Funding ◽  
Plasma Cells ◽  
Poems Syndrome ◽  
Multiparameter Flow Cytometry ◽  
Clone Size ◽  
Aberrant Expression ◽  
Identification Rate ◽  
Company Limited ◽  
Cd56 Expression

Abstract Introduction POEMS syndrome is a rare systemic disorder characterized by various symptoms, including polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy (M-protein), and skin changes, which is based on the presence of monoclonal plasma cells (PC). We previously reported the analysis of the clonal immunoglobulin λ light-chain variable region (IGLV) gene rearrangements in POEMS syndrome using next-generation sequencing (NGS), and the clone identification rate was 36.7% (Kawajiri-Manako C, Am J Hematol. 2018;93(9):1161). EuroFlow-based next-generation flow (EuroFlow-NGF) has also been standardized for detecting minimal residual disease in multiple myeloma (MM). However, multiparameter flow cytometry (MFC) utility in detecting clonal PC of POEMS syndrome remains unknown. Therefore, to clarify the feasibility of detecting the clonality with MFC, we analyzed PC of bone marrow samples in patients with POEMS syndrome by MFC and validated gating strategies of PC in POEMS syndrome. Methods Patients with newly diagnosed or relapsed POEMS syndrome (n=25) at Chiba University Hospital from April 2019 to July 2021 were included in this study. Primary bone marrow aspirations were performed after obtaining informed consent following the Declaration of Helsinki. The collected bone marrow samples were analyzed by the SRL-Flow protocols (single-tube 8-color: CD138/CD27/CD38/CD56/CD45/CD19/CyIgκ/CyIgλ), which is highly correlated with EuroFlow-NGF (Takamatsu H, Int J Hematol. 2019;109(4): 377). Furthermore, 21 cases for which data files were available from SRL Inc. were reanalyzed by gating PC with lower expression of CD45 regarding the previous study (Dao LN, Blood. 2011;117(24):6438). This study was approved by the ethics committee of Chiba University Graduate School of Medicine. Results Among 25 patients, the median age was 59 (25-77) years, and 13 (52.0%) were men. The types of M-proteins identified by immunofixation electrophoresis (IFE) were IgA-λ in 12 (48.0%), IgG-λ in 9 (36.0%), IgA-κ in 1 (4.0%), IgG-κ in 1 (4.0%), and negative in 2 patients (8.0%), respectively. The median serum VEGF level was 3,240 (747-9,060) pg/ml. SRL-Flow identified the clonal PC in 9 of 25 (36.0%, λ in 7 and κ in 2): 7 of 23 IFE-positive cases (30.4%) and 2 of 2 IFE-negative cases (100%). The median clone size was 0.03 (0.01-3.78)%, smaller than MM. Interestingly, the clone size was not correlated with the level of serum VEGF (r = -0.17). Aberrant expression of clonal PC in POEMS syndrome was similar to MM: CD19-56+ in 5 (55.6%), CD19-56- in 2 (22.2%), CD19dim56- in 1 (11.1%), and CD19-56dim in 1 (11.1%) patient, respectively. No clone was detected in PC with CD19+56-. The clone identification rate by single-tube 8-color SRL-Flow protocols was lower than expected. Therefore, we reanalyzed the data by gating PC with lower expression of CD45 and CD38. In the reanalysis, we gated broadly for CD38 dim-to-bright and CD138 dim-to-bright cells and narrowly for CD38 dim and CD45 negative-to-dim cells. As a result, we identified the clonal PC in 15 of 21 cases (71.4%, λ in 13 and κ in 2): 13 of 19 IFE-positive cases (68.4%) and 2 of 2 IFE-negative cases (100%)). Of the 15 cases in which monoclonal PC were identified by reanalysis, 8 were negative by SRL-Flow. Of these, 6 were identified by selective gating of CD45- and CD38 dim, and 2 were identified by selective gating of CD45- and CD38+. The median clone size was 0.008 (0.001-3.27)%, smaller than that of MM, and the clone size was not correlated with the level of serum VEGF (r = -0.15). The aberrant expression of the clonal PC in POEMS remained similar to MM for CD19 and CD56 expression: CD19-56+ in 3 (20.0%), CD19-56- in 7 (46.7%), CD19-56dim in 4 (26.7%), and CD19dim 56- in 1 (6.7%) patient, respectively. No clone was detected in PC with CD19+56-. Conclusions EuroFlow-based SRL-Flow protocols detected the clonal PC in about one-third of POEMS patients. Aberrant immunophenotype of clonal PC in POEMS syndrome was similar to MM for CD19 and CD56 expression; however, CD45 and CD38 expression of POEMS PC tended to be downregulated. Selective gating of PC with CD38dim and CD45 negative-to-dim detected clonal PC in 71.4% of cases. This novel gating strategy is more accessible and might improve the identification rate of clonal PC in POEMS syndrome. Disclosures Tsukamoto: Daiichi Sankyo: Honoraria. Yokote: Kowa Company, Ltd.: Honoraria, Other: Scholarship; MSD K.K.: Honoraria, Other: Scholarship, Courses endowed by company; Astellas Pharma Inc.: Honoraria, Other: Scholarship; Mitsubishi Tanabe Pharma Corporation: Honoraria, Other: Scholarship; Amgen K.K.: Honoraria; Taisho Pharmaceutical Co., Ltd.: Honoraria, Other: Scholarship, Research Funding; Nippon Boehringer Ingelheim Co., Ltd.: Honoraria, Other: Scholarship; Janssen Pharmaceutical K.K.: Honoraria; Kao Corporation: Other: Schlarship; Novo Nordisk Pharma Ltd.: Honoraria, Other: Scholarship; Teijin Pharma Limited: Other: Scholarship; Pfizer Japan Inc.: Honoraria, Other: Scholarship; Kyowa Kirin Co., Ltd.: Honoraria; Eli Lilly Japan K.K.: Honoraria, Other: Scholarship; Takeda Pharmaceutical Company Limited: Honoraria, Other: Scholarship; Sanofi K.K.: Honoraria; Ono Pharmaceutical Co., Ltd: Honoraria, Other: Scholarship; AstraZeneca K.K.: Honoraria; Daiichi Sankyo Company, Limited: Honoraria, Other: Scholarship; Novartis Pharma K.K.: Honoraria; Sumitomo Dainippon Pharma Co., Ltd.: Honoraria, Other: Scholarship; Shionogi Co., Ltd.: Other: Scholarship; Bayer Yakuhin, Ltd.: Other: Scholarship. Nakaseko: Novartis Pharma KK.: Honoraria. Takamatsu: Adaptive Biotechnologies, Eisai: Honoraria; SRL: Consultancy; Bristol-Myers Squibb: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding. Sakaida: Bristol Myers Squibb: Research Funding; Chugai: Research Funding; Ono: Research Funding; Kyowa Kirin: Research Funding.

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