Incidence, clinical course, and prognosis of secondary monoclonal gammopathy of undetermined significance in patients with multiple myeloma

Wadhera, Rishi K.; Kyle, Robert A.; Larson, Dirk R.; Dispenzieri, Angela; Kumar, Shaji; Lazarus, Hillard M.; Rajkumar, S. Vincent

doi:10.1182/blood-2011-04-349175

Cited by 35 publications

(65 citation statements)

References 25 publications

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“…17) developed secondary MGUS after being diagnosed with biopsy-proven autologous GVHD. 7 Wadhera and associates 16 at the Mayo Clinic recently reported their experiences in 1942 PCM patients. Secondary MGUS was significantly more common in hematopoietic cell transplant recipients than in PCM subjects who had not received this therapy (22.7% vs 1.6%, respectively, Po0.001).…”

Section: Resultsmentioning

confidence: 99%

Secondary MGUS after autologous hematopoietic progenitor cell transplantation in plasma cell myeloma: a matter of undetermined significance

Manson

Campagnaro

Balog

et al. 2011

Bone Marrow Transplant

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Plasma cell myeloma, characterized by clonally aberrant plasma cells that produce abnormal monoclonal Igs, is the most common indication for autologous hematopoietic progenitor cell transplantation (AHPCT) in North America. We observed appearance of new monoclonal gammopathies different from the original protein in the post-AHPCT setting and termed this condition 'secondary MGUS' (monoclonal gammopathy of undetermined significance). Hence, we performed a retrospective, single institution review of serum protein electrophoresis/immunofixation electrophoresis data in 92 AHPCT recipients from the period 2000 --2009. In all, 22 of 92 patients (24%) undergoing AHPCT met criteria for secondary MGUS. Contrary to previous studies, often referred to as 'abnormal protein banding,' we did not observe this condition as a favorable prognostic indicator in affected patients when compared with the control group (P ¼ 0.686). However, we did note that a subgroup of the study cohort who developed secondary MGUS after a prolonged latency (410 months) had an improved median OS compared with the remainder of the study cohort (75 months vs 41 months, P ¼ 0.005). As there have been significant advancements in understanding the pathobiology and clinical significance of MGUS, we believe that secondary MGUS merits dedication of resources for investigation to determine its true clinical relevance, prognostic value and pathophysiology.

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Section: Resultsmentioning

confidence: 99%

Secondary MGUS after autologous hematopoietic progenitor cell transplantation in plasma cell myeloma: a matter of undetermined significance

Manson

Campagnaro

Balog

et al. 2011

Bone Marrow Transplant

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“…Further, information about isotype and electrophoretic migration position is needed when following response to therapy so that one may distinguish relapse of the original clone from the development of oligoclonal bands and/or a second (usually reactive) M-protein. Such additional M-proteins commonly occur after autologous stem cell transplants with rates as high as 73% being reported [7][8][9][10]. The development of oligoclonal bands and/or a second M-protein following autologous stem cell transplantation in MM has been reported to be a favorable prognostic sign for most patients [11].…”

Section: Introductionmentioning

confidence: 99%

Challenges of measuring monoclonal proteins in serum

Keren

Schroeder

2016

Clinical Chemistry and Laboratory Medicine (CCLM)

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Abstract:The measurement of monoclonal protein (M-protein) is vital for stratifying risk and following individuals with a variety of monoclonal gammopathies. Direct measurement of the M-protein spike by electrophoresis and immunochemical measurements of specific isotypes or free light chains pairs has provided useful information about the quantity of M-protein. Nonetheless, both traditional electrophoresis and immunochemical methods give poor quantification with M-proteins smaller than 10 g/L (1 g/dL) when in the presence of polyclonal immunoglobulins that co-migrate with the M-protein. In addition, measurements by electrophoresis of M-proteins migrating in the β-and α-regions are contaminated by normal serum proteins in those regions. The most precise electrophoretic method to date for quantification involves exclusion of the polyclonal immunoglobulins by using the tangent skimming method on electropherograms, which provides a 10-fold improvement in precision. So far, however, tangent measurements are limited to γ migrating M-proteins. Another way to improve M-protein measurements is the use of capillary electrophoresis (CE). With CE, one can employ immunosubtraction to select a region of interest in the β region thereby excluding much of the normal proteins from the M-protein measurement. Recent development of an immunochemical method distinguishing heavy/light chain pairs (separately measuring IgGK and IgGL, IgAK and IgAL, and IgMK and IgML) provides measurements that could exclude polyclonal contaminants of the same heavy chain with the uninvolved light chain type. Yet, even heavy/light results contain an immeasurable quantity of polyclonal heavy/ light chains of the involved isotype. Finally, use of liquid chromatography-tandem mass spectrometry (LC-MS/MS) looms on the horizon as a means to provide more consistent and sensitive measurements of M-proteins.

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“…The data that needs to be accumulated at diagnosis to establish prognosis can be exhaustive, including standard/ specialized biochemical tests, cytogenetics, specialized staining/flow cytometry and extensive X-ray/MRI analysis [4][5][6][7]. Unfortunately, for a variety of reasons, this plethora of data is regularily not available and a clinician may be faced with not even being able to accurately stage the patient, the very basic of prognostic indicators.…”

Section: Discussionmentioning

confidence: 99%

“…There are a number of factors that influence a MM patient's prognosis and response to therapy [3][4][5][6][7] including: disease stage, renal impairment, tumor burden, severity of anaemia, proliferation index of the plasma cells (PCPI) and chromosomal abnormalities. The International Staging System (ISS), is based on levels of β 2 microglobulin (B2M) and albumin, and the Durie-Salmon Staging (DSS) index that looks at M-protein levels, the presence of bone lesions, haemoglobin (Hb), calcium and serum creatinine levels [8,9].…”

Section: Introductionmentioning

confidence: 99%

Cancer/Testis Antigen Expression Panel Incorporating MAGEC1 and BAGE2 Predicts Multiple Myeloma Disease Stage and Severity

Shires

Teuchert²,

Wienand³

et al. 2016

J Hematol Thrombo Dis

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To provide a single molecular assay that could be used to easily stage Multiple Myeloma patients at diagnosis, we investigated the association between the simultaneous expression of 7 Multiple Myeloma-associated Cancer/Testis Antigens and biochemical parameters that are currently used for disease staging. We analysed the mRNA expression of MAGEC1, MAGEA3/A6, BAGE2, PRAME, NYESO1, SSX2 and PAGE by qualitative reverse transcription PCR using RNA extracted from diagnostic bone marrow samples from 39 patients covering the Multiple Myeloma disease continuum and compared this to levels of key biochemical parameters at diagnosis. We found that the Cancer/Testis Antigen panel was expressed in a specific order that was specifically associated with the severity of disease. This allowed the Cancer/Testis Antigens expression profile to successfully place the patient clearly into either stage I or stage III of the disease, with further sub-stratification in the stage III grouping. In addition, we putatively identified MAGEC1 expression as a confirmatory diagnostic marker for symptomatic Multiple Myeloma and clearly associated BAGE2 expression exclusively with stage III disease. We also demonstrated the novel finding of PAGE expression in Multiple Myeloma, with an association with more advanced disease. We suggest that this particular molecular Cancer/Testis Antigen panel can be used at diagnosis as a single test to clearly stage patients.

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Incidence, clinical course, and prognosis of secondary monoclonal gammopathy of undetermined significance in patients with multiple myeloma

Cited by 35 publications

References 25 publications

Secondary MGUS after autologous hematopoietic progenitor cell transplantation in plasma cell myeloma: a matter of undetermined significance

Secondary MGUS after autologous hematopoietic progenitor cell transplantation in plasma cell myeloma: a matter of undetermined significance

Challenges of measuring monoclonal proteins in serum

Cancer/Testis Antigen Expression Panel Incorporating MAGEC1 and BAGE2 Predicts Multiple Myeloma Disease Stage and Severity

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