Dynamic Contrast-Enhanced Magnetic Resonance Imaging Identifies a Subgroup of Patients with Asymptomatic Monoclonal Plasma Cell Disease and Pathologic Microcirculation

Hillengaß, Jens; Zechmann, Christian M.; Bäuerle, Tobias; Wagner-Gund, Barbara; Heiß, Christian; Benner, Axel; Ho, Anthony D.; Neben, Kai; Hose, Dirk; Kauczor, Hans‐Ulrich; Goldschmidt, Hartmut; Delorme, Stefan; Michel, Thomas

doi:10.1158/1078-0432.ccr-08-2310

Cited by 53 publications

(39 citation statements)

References 37 publications

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“…[7][8][9]30 Abnormal bone marrow appearance on an MRI can be detected in a fraction of patients with asymptomatic MM and reportedly can predict an increased risk of progression to symptomatic disease. [7][8][9]30 In our survival analysis, the presence of MRI abnormalities was associated with a higher (although not significant) probability of progression (cumulative probability of progression at 5 years, 50.1% vs 23.9%; P ¼ .110).…”

Section: Discussionmentioning

confidence: 99%

Beta‐2‐microglobulin is an independent predictor of progression in asymptomatic multiple myeloma

Rossi

Fangazio

Paoli

et al. 2010

Cancer

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BACKGROUND: Although serum beta-2 microglobulin (B2M) represents a key variable for symptomatic multiple myeloma (MM) prognostication, its role in predicting the risk of progression of asymptomatic MM to symptomatic disease has not been explored. METHODS: This study was bases on a consecutive series of 148 patients with asymptomatic MM and explored the cumulative probability of progression to symptomatic MM as the primary endpoint. RESULTS: In univariate analysis, a serum B2M level >2.5 mg/L was associated with an increased probability of disease progression (5-year risk, 64.5%; P < .001) along with serum monoclonal component (sMC) (P < .001), urinary monoclonal component (uMC) (P < .001), and bone marrow plasma cells (BMPCs) (P < .001). In multivariate analysis, serum B2M was selected as an independent predictor of progression (hazard ratio, 3.30; P ¼.002). Serum B2M was combined with sMC, uMC, and BMPC to create a risk-stratification model based on 4 groups with different risk of progression: very low (5-year risk, 0%), low-intermediate (5-year risk, 19.6%), high-intermediate (5-year risk, 60.7%), and high (5-year risk, 80.7%). The model that included serum B2M along with sMC, uMC, and BMPC was able to predict disease progression better than the model that was based on sMC, uMC, and BMPC without serum B2M (C statistics, 0.760 vs 0.726). CONCLUSIONS: The current results indicated that 1) serum B2M is an independent predictor of asymptomatic MM progression, and 2) serum B2M adds prognostic information when combined with the most widely used prognosticators of asymptomatic MM progression.

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Section: Discussionmentioning

confidence: 99%

Beta‐2‐microglobulin is an independent predictor of progression in asymptomatic multiple myeloma

Rossi

Fangazio

Paoli

et al. 2010

Cancer

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“…62 Differences with regard to cellular and secreted components of the microenvironment have also been observed in MGUS compared with MM patients. 63 Conversion from precursor to full-blown disease has been proposed to be related to an "angiogenic switch" resulting from an alteration in the milieu of pro-and anti-angiogenic cytokines allowing for malignant proliferation [64][65][66] . Finally, microRNAs, short, noncoding RNA sequences that modulate many biological processes by pairing with target mRNAs and regulating their expression, 67 have been implicated as playing a role in myelomagenesis.…”

Section: Need For Better Molecular and Immunophenotypic Markersmentioning

confidence: 99%

Monoclonal Gammopathy of Undetermined Significance and Smoldering Myeloma: New Insights into Pathophysiology and Epidemiology

Landgren

2010

Hematology

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Routine screening for monoclonal gammopathy of undetermined significance (MGUS) is not indicated. Despite this fact, MGUS is a common finding in medical practice. Almost all individuals diagnosed with MGUS represent incidental cases diagnosed when physicians order serum protein electrophoresis, immunofixation, or both, as part of the work-up of a number of common symptoms and laboratory abnormalities. In the absence of reliable molecular predictors of outcome, the detection of an early precursor state typically imposes a complex situation for the patient and the responsible physician-usually, it leads to a lot of questions that lack clear answers. In the past years, several novel insights have been gained in the area of multiple myeloma (MM) precursor disease. This review focuses on results from recent investigations and discusses implications for diagnostic work-up, clinical management, and patient counseling. More specifically, it sheds light on the following commonly asked questions by patients and physicians: i) what is the risk of progression from precursor to full-blown MM, and are there ways to risk-stratify patients?; ii) is MM always preceded by a precursor state, and is there anything that could or should be done to delay or prevent progression?; and iii) why do some individuals develop MM precursor diseases, and is there a reason to screen the family? Definitions and Epidemiology From 'Benign Monoclonal Protein' to Monoclonal Gammopathy of Undetermined SignificanceThe concept of monoclonal versus polyclonal gammopathies was initially raised in 1960 by Jan Waldenström, 1 who described patients with a narrow band of hypergammaglobulinemia on electrophoresis as having a monoclonal-or M-protein. Many of these patients had multiple myeloma (MM) or macroglobulinemia, while others had no evidence of malignancy. Waldenström considered these patients to have "essential hypergammaglobulinemia" or a "benign monoclonal protein."Based on the observation that otherwise healthy individuals with these protein abnormalities turned out to have an excess risk of developing MM, Waldenströ m's macroglobulinemia, light-chain amyloidosis, or related disorders, Robert Kyle coined the term "monoclonal gammopathy of undetermined significance" (MGUS) in 1978. 2 According to diagnostic criteria provided by the International Myeloma Working Group (IMWG) in 2010, 3 MGUS is defined as follows (and all three criteria must be met): i) serum monoclonal protein under 3 g/dL; ii) clonal bone marrow plasma cells under 10%; and iii) absence of end-organ damage such as hypercalcemia, renal insufficiency, anemia, and bone lesions that can be attributed to the plasma-cellproliferative disorder.Screening studies have found MGUS to be present in approximately 3.2% of Caucasians above the age of 50 years. 4 Prevalence appears to be roughly twice as high among African men, African-American women, and obese individuals. 5,6 Chronic antigen stimulation 7-11 and pesticide exposure have also been associated with an excess risk of MGUS/MM. 12,13 Rece...

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“…Correspondingly, patients with multiple myeloma show a higher bone marrow microvessel density (MVD) than patients with SMM, MGUS, or healthy individuals (3). Increased bone marrow microcirculation is associated with adverse outcome in patients with multiple myeloma (4,5) as well as SMM (6), and angiogenesis is directly linked to the development of multiple myeloma-related bone disease (7,8). Furthermore, patients in remission after therapy showed a significantly decreased MVD compared with those with residual disease (9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

“…Dynamic contrast-enhanced MRI (DCE-MRI) is a noninvasive imaging modality to study bone marrow microcirculation in patients with monoclonal plasma cell diseases (6,(13)(14)(15). In patients with solid tumors, it has become a valuable tool to quantify treatment response beyond measuring tumor size.…”

Section: Introductionmentioning

confidence: 99%

Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Assessment of Antiangiogenic Treatment Effects in Multiple Myeloma

Merz

Ritsch

Kunz

et al. 2015

Clinical Cancer Research

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Purpose: To noninvasively assess bone marrow microcirculation before and after therapy in patients with newly diagnosed multiple myeloma with dynamic contrast-enhanced MRI (DCE-MRI).Experimental Design: Ninety-six patients received DCE-MRI before and after primary treatment for newly diagnosed multiple myeloma. For the 91 evaluable patients, treatment consisted of high-dose therapy (HDT) with autologous stem cell transplantation (ASCT) in 82 patients and chemotherapy without ASCT in 9 patients. In addition, 33 healthy volunteers were imaged as the control group. Analysis of DCE-MRI was performed according to the two-compartment model by Brix to quantify amplitude A (associated with blood volume) and exchange rate constant k ep (reflecting vessel permeability and perfusion).Results: Nonresponders showed significantly higher A-values before the start of therapy compared with responders (P ¼ 0.02). In both responders and nonresponders to therapy, A-values dropped significantly (P ¼ 0.004 and <0.001, respectively) after primary therapy, whereas lower values for k ep were found only in responders (P < 0.001). Depth of remission was significantly correlated to decreased bone marrow microcirculation: Patients in near complete response (nCR) or complete remission (CR) after treatment showed significantly lower values for A compared with patients not achieving nCRþCR. The application of HDT or novel agents had no significant effect on DCE-MRI parameters after therapy, although patients treated with novel agents more often achieved nCRþCR (42%/12.5%; P < 0.002). Higher k ep -values at second MRI were positively correlated to shorter overall survival (HR 3.53; 95% confidence intervals, 1.21-10.33; P ¼ 0.02).Conclusion: Parameters from DCE-MRI are correlated to remission after primary therapy and outcome in newly diagnosed multiple myeloma.

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Dynamic Contrast-Enhanced Magnetic Resonance Imaging Identifies a Subgroup of Patients with Asymptomatic Monoclonal Plasma Cell Disease and Pathologic Microcirculation

Cited by 53 publications

References 37 publications

Beta‐2‐microglobulin is an independent predictor of progression in asymptomatic multiple myeloma

Beta‐2‐microglobulin is an independent predictor of progression in asymptomatic multiple myeloma

Monoclonal Gammopathy of Undetermined Significance and Smoldering Myeloma: New Insights into Pathophysiology and Epidemiology

Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Assessment of Antiangiogenic Treatment Effects in Multiple Myeloma

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