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.

New Criteria To Identify Risk of Progression in Monoclonal Gammopathy of Uncertain Significance: Multiparametric Flow Cytometry Analysis of Bone Marrow Plasma Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3517-3517
Author(s):  
Ernesto Perez-Persona ◽  
María-Belén Vidriales ◽  
Gema Mateo ◽  
Ramón Garcia Sanz ◽  
Marivi Mateos ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Flow Cytometry Analysis ◽  
Dna Index ◽  
Multiparametric Flow Cytometry ◽  
Uncertain Significance ◽  
Risk Of Progression ◽  
Bone Marrow Plasma

Abstract Monoclonal Gammopathy of Uncertain Significance (MGUS) is a monoclonal disorder defined by the presence of a serum monoclonal protein <3g/dL, bone marrow plasma cells < 10% and absence of end-organ damage. The risk of progression to multiple myeloma (MM) is about 1% per year, and therefore these patients require long follow-up. Accordingly, the definition of new parameters that could be used for the identification of patients at risk of progression could be of great value. The aim of the present study is to evaluate the utility of multiparameter flow cytometry analysis of bone marrow (BM) plasma cells (PC) for predicting the risk of progression of MGUS patients. From January 1996 to September 2004, bone marrow aspirate samples from 350 patients, who fulfil the criteria of MGUS according to the International Myeloma Working Group criteria, were analysed by multiparametric flow cytometry. A specific gate on PC was performed based on CD138/CD38 expression and FSC/SSC characteristics and PC were immunophenotypically classified as normal (polyclonal) or aberrant (clonal) according to the expression of CD138, CD38, CD45, CD19 and CD56 antigens. Twenty seven patients (8 %) progressed to MM, with a median time to progression (TTP) of 46 months (range 9 to 109 months). Interestingly, the percentage of aberrant PC within the total BM PC compartment (aPC/BMPCc) clearly identify patients at different risk of progression. Thus, TTP in patients with ≥ 95% aPC/BMPCc was 85 months vs not reached cases with <95% aPC/BMPCc (p=0.0000). Other parameters with a significant influence on progression in the univariate analysis were: paraprotein level (higher vs lower of 2 mg/dl; p= 0.0004), the presence of immunoparesis (no paresis vs. decreased levels in one or two Ig. p= 0.0005), Bence-Jones proteinuria (p= 0.0003), PC BM infiltration assessed both by morphology and flow cytometry (p=0.0074; and p= 0.001, respectively), and DNA index assessed by flow cytometry (diploid vs aneuploid; p=0.0064). Moreover, the cut off level of 95% aPC/BMPCc, also allows the discrimination of two risk categories upon considering only patients at low risk of progression, based on a low paraprotein level or absence of inmunoparesis (p= 0.0000 and p= 0.0000, respectively). On multivariate analysis only the percentage of aPC/BMPCc (≥95%) (p=0.000), the DNA index (p=0.007), and the Bence-Jones proteinuria (p=0.000) showed independent prognostic value. In summary, our results show that multiparameter FC evaluation of BMPC at diagnosis is a simple, cost-effective and valuable tool for predicting the risk of progression of MGUS patients.

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

2021 ◽  
Vol 11 ◽  
Author(s):  
Veronika Riebl ◽  
Sandra Maria Dold ◽  
Dagmar Wider ◽  
Marie Follo ◽  
Gabriele Ihorst ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Flow Cytometry ◽  
Disease Burden ◽  
Outcome Prediction ◽  
Plasma Cells ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Multiparameter Flow Cytometry ◽  
Highly Sensitive

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.

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 Donor-Derived Smoldering Multiple Myeloma following a Hematopoietic Cell Transplantation for AML

2017 ◽  
Vol 2017 ◽  
pp. 1-3
Author(s):  
Bita Fakhri ◽  
Mark Fiala ◽  
Michael Slade ◽  
Peter Westervelt ◽  
Armin Ghobadi
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cell Transplantation ◽  
Monoclonal Gammopathy ◽  
Hematopoietic Cell Transplantation ◽  
Plasma Cells ◽  
Hematopoietic Cell ◽  
Unrelated Donor ◽  
Solid Organ ◽  
Smoldering Multiple Myeloma

Posttransplant Lymphoproliferative Disorder (PTLD) is one of the most common malignancies complicating solid organ transplantation. In contrast, PTLD accounts for a minority of secondary cancers following allogeneic hematopoietic cell transplantation (HCT). Here we report on a 61-year-old woman who received an ABO-mismatched, HLA-matched unrelated donor hematopoietic cell transplantation from a presumably healthy donor for a diagnosis of acute myeloid leukemia (AML). Eighteen months following her transplant, she developed a monoclonal gammopathy. Bone marrow studies revealed 10% plasma cells, but the patient lacked clinical defining features of multiple myeloma (MM); thus a diagnosis of smoldering multiple myeloma (SMM) was established. Cytogenetic and molecular studies of the bone marrow confirmed the plasma cells were donor-derived. The donor lacks a diagnosis of monoclonal gammopathy of undetermined significance, SMM, or MM.

Immunoglobulin Free Light Chain Ratio Is an Independent Risk Factor for Progression of Smoldering Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1487-1487 ◽  
Author(s):  
Angela Dispenzieri ◽  
Robert A. Kyle ◽  
Jerry A. Katzmann ◽  
Dirk Larson ◽  
Joanne Benson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Light Chain ◽  
Plasma Cells ◽  
Free Light Chain ◽  
M Protein ◽  
Baseline Serum ◽  
Smoldering Multiple Myeloma ◽  
Risk Of Progression ◽  
Bone Marrow Plasma

Abstract Background: Smoldering multiple myeloma (SMM) is an asymptomatic plasma cell proliferative disorder with a high risk of progression to symptomatic multiple myeloma. Identification of risk factors that predict progression of SMM to symptomatic MM could identify higher risk patients who might benefit from chemoprevention or more intensive surveillance. We hypothesized that increased monoclonal free kappa or lambda immunoglobulin light chains in smoldering myeloma (SMM), as detected by the serum free light chain (FLC) assay, indicates an increased the risk of progression to active myeloma. Methods: Of 276 pathologically confirmed SMM patients seen at the Mayo Clinic from 1970 to 1995, baseline serum samples obtained within 30 days of diagnosis were available in 273. Results: At a median follow-up of surviving patients of 12.4 years, transformation to active disease has occurred in 161 (59%) patients. An abnormal FLC ratio was present at baseline in 90% of patients. The best break-point for predicting risk of progression was a FLC ratio less than or equal to 0.125 or greater than or equal to 8 (hazard ratio, 2.3; 95% CI, 1.6–3.2) [Figure 1]. The extent of abnormality of FLC ratio was independent of SMM risk categories defined by number of plasma cells in the bone marrow and size of serum M-proteins (bone marrow plasma cells ≥ 10% and serum M protein ≥ 3 g/dL; bone marrow plasma cells ≥ 10% but serum M protein &lt; 3 g/dL; and serum M protein ≥ 3 g/dL but bone marrow plasma cells &lt; 10%). Incorporating the FLC ratio into the risk model, the division of patients into high-, intermediate-, and low-risk groups is 28, 42, and 30% with 5 year progression rates of 76, 51, and 25%, respectively [Figure 2]. Conclusions: The serum immunoglobulin FLC ratio is an important additional determinant of clinical outcome in patients with SMM. Figure Figure Figure Figure

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.

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