Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance

Rajkumar, S. Vincent; Kyle, Robert A.; Therneau, Terry M.; Melton, L. Joseph; Bradwell, Arthur R.; Clark, Raynell J.; Larson, Dirk R.; Plevak, Matthew F.; Dispenzieri, Angela; Katzmann, Jerry A.

doi:10.1182/blood-2005-03-1038

Cited by 570 publications

(491 citation statements)

References 26 publications

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“…6,7 There are also data to suggest that MGUS cases with an abnormal serum-free light chain ratio, non-IgG MGUS and a high-serum M-protein level (X15 g/l) have a 58% absolute risk of developing MM after 20 years of follow-up; in contrast, MGUS cases with none of these risk factors have only a 5% absolute risk of progressing to MM. 4 These observations show a wide variation in the risk of progression to MM among MGUS patients and, importantly, the vast majority of MGUS cases will never develop a lymphoproliferative malignancy. 4 A recent study based on 77 469 healthy adults enrolled in a US nationwide population-based prospective cancer screening trial identified 71 individuals who developed MM during the course of the study.…”

Section: Introductionmentioning

confidence: 87%

“…3 It is characterized by the presence of a monoclonal immunoglobulin (Ig) (M-protein) without evidence of MM or other lymphoproliferative malignancies. 4,5 Based on data from the Mayo Clinic, long-term follow-up of MGUS patients reveals an average 1% annual risk of developing a lymphoproliferative malignancy. 6,7 There are also data to suggest that MGUS cases with an abnormal serum-free light chain ratio, non-IgG MGUS and a high-serum M-protein level (X15 g/l) have a 58% absolute risk of developing MM after 20 years of follow-up; in contrast, MGUS cases with none of these risk factors have only a 5% absolute risk of progressing to MM.…”

Section: Introductionmentioning

confidence: 99%

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Patterns of monoclonal gammopathy of undetermined significance and multiple myeloma in various ethnic/racial groups: support for genetic factors in pathogenesis

2009

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Monoclonal gammopathy of undetermined significance (MGUS) is one of the most common premalignant disorders in Western countries. Recent studies show that almost every multiple myeloma (MM) case is preceded by an MGUS stage. Interestingly, prevalence and incidence patterns for MGUS and MM show striking disparity patterns across ethnic/racial groups, most notably the two-to threefold increase in both these disorders in African Americans compared with Caucasians. In contrast, studies on Asian patients show lower prevalence/ incidence for MGUS/MM compared with Caucasians. Familial aggregation for both MGUS and MM has been observed; the risk for MGUS or MM in family members with these disorders is increased about two-to three fold compared with the general population. Although underlying mechanisms remain unclear, there is evidence of heterogeneity among MGUS patients from different ethnic/racial groups. For example, compared with Caucasians, African-American and African MGUS patients have reportedly lower rates of immunoglobulin M (IgM) MGUS (versus IgG/IgA MGUS) and higher rates of unquantifiable immunoglobulins (Igs). This review focuses on racial disparity and familial aggregation patterns for MGUS and MM and discusses how these observations provide novel clues with regard to pathogenesis.

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Section: Introductionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Patterns of monoclonal gammopathy of undetermined significance and multiple myeloma in various ethnic/racial groups: support for genetic factors in pathogenesis

2009

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“…In a large study of 1,148 MGUS patients at the Mayo Clinic, the 379 (33%) patients with an abnormal serum FLC ratio had a significantly increased risk of progression to myeloma, with a hazard ratio of 3.5 (P < 0.001, CI 2.3-5.5) [17]. In a separate study of 116 patients with SBP, 43 patients had progressed to myeloma by 5 years.…”

Section: Clinical Applicationsmentioning

confidence: 97%

Serum free light chain analysis

2010

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In a variety of hematologic malignancies, immunoglobulin light chains (LC) are overproduced clonally and circulate without being linked by disulphide bonds to the immunoglobulin heavy chain. The recent development of a robust assay known as j and k ''free'' LC (FLC) to quantify the levels of these unbound LC in the serum, and thereby determine their ratio, has led to an explosion of studies that demonstrate its utility in a wide range of hematologic disorders. This article summarizes laboratory testing for serum FLC, with a particular focus on clinical applications for the test. Am. J. Hematol. 85:787-790, 2010. V V C 2010 Wiley-Liss, Inc. BackgroundHematologic malignancies frequently result in the production of monoclonal immunoglobulin. Detection of both intact immunoglobulin and immunoglobulin free light chains (FLC) in the urine and blood has proven to be valuable in the diagnosis, prognosis, and monitoring of treatment of these diseases. One particularly useful property of serum FLC is their short half-life in the blood (j, 2-4 hrs; k, 3-6 hrs) in comparison to intact immunoglobulin (21 days), which provides an opportunity for real-time monitoring of disease progression and response to treatment.For well over a century, testing for the presence of Bence Jones (BJ) protein in the urine was considered to be the gold standard to assess the clonally abnormal levels of immunoglobulin FLC. This technique can detect FLC down to the range of 10-40 mg/L; however, it can be challenging to obtain an accurate 24 hr urine collection, which is necessary for the test [1]. Moreover, due to the high resorptive capabilities of the proximal tubules of the kidney or reduced renal function, patients with low levels of FLC in the serum may not have detectable amounts in the urine [2]. Quantitative alterations of serum immunoglobulins (Igs) may result from polyclonal or monoclonal disorders. The combination of serum protein electrophoresis (SPEP), immunofixation (IFE), and densitometric analysis permits characterization and quantitation of the monoclonal immunoglobulin; however, the sensitivity of SPEP to detect FLC is poor, with a lower limit of sensitivity of 500-2,000 mg/L. Although the IFE does improve sensitivity for the detection of FLC (lower limit of sensitivity 150-500 mg/L), it is a more time-intensive assay and does not allow for quantification. Technical Aspects, Performance, and LimitationsThe development of an accurate and reproducible serum assay to determine j and k FLC concentration with high sensitivity has been a major challenge. A significant barrier to the development of the test is the fact that the unique epitope that is a marker of FLC is ''hidden'' or concealed in the conformational structure of an intact Ig. This precluded the development of a tool such as a specific antibody to detect the ''hidden epitope'' of FLC. This barrier was overcome in 2001 by Bradwell and coworkers [3], who dissociated the FLC from heavy chains and then raised polyclonal antibodies to detect the unique epitopes on j and k LC. T...

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“…19 There is no single prognostic marker to determine which patients will progress, but a serum monoclonal protein level of greater than 1.5 g/dL, a non-IgG monoclonal immunoglobulin, and abnormal serum free light chain ratio are known risk factors for progression ( Table 2). 22,23 Because the risk of progression does not decrease over time, patients with MGUS require lifelong monitoring. It has been suggested that patients with low-risk disease can be monitored by history and physical (HP) only for signs or symptoms of disease progression and do not necessarily need routine laboratory monitoring.…”

Section: MMmentioning

confidence: 99%

Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma in Older Adults

Guerard

Tuchman

2016

Clinics in Geriatric Medicine

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Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance

Cited by 570 publications

References 26 publications

Patterns of monoclonal gammopathy of undetermined significance and multiple myeloma in various ethnic/racial groups: support for genetic factors in pathogenesis

Patterns of monoclonal gammopathy of undetermined significance and multiple myeloma in various ethnic/racial groups: support for genetic factors in pathogenesis

Serum free light chain analysis

Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma in Older Adults

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