Evaluation of Prognostic Factors for Malignant Transformation of Monoclonal Gammopathy of Undetermined Significance

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5123-5123
Author(s):  
Federico Sackmann ◽  
Claudia Corrado ◽  
Isolda Fernandez ◽  
Miguel A Pavlovsky ◽  
Pablo Mountford ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Malignant Transformation ◽  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Bone Lesions ◽  
Monoclonal Protein ◽  
Lytic Bone Lesions ◽  
Beta 2 ◽  
Beta 2 Microglobulin ◽  
Undetermined Significance

Abstract Background: monoclonal gammopathy of undetermined significance (MGUS) has a prevalence of 1 to 3%. Although it has an indolent evolution, some patients (pts) will develop a malignant transformation. Thus, prognostic factors that may identify pts who will progress are important. We update our experience published before. Methods: we performed a retrospective analysis of 387 pts with MGUS diagnosed between 1982 and 2008 in our institution to identify simple haematological variables associated with progression. Actuarial progression free survival (PFS) and overall survival (OS) were also calculated. MGUS was diagnosed when monoclonal component (MC) was present at a concentration of 3 gr per decilitre or less, no or only moderate amounts of monoclonal light chains in the urine, absence of lytic bone lesions, anemia, hypercalcemia and renal insufficiency related to monoclonal protein; and if performed a proportion of plasma cells of 10 percent or less. MC was detected by agarose gel and/or cellulose acetate electrophoresis in serum and/or urine. The identification of the MC was performed by immunoelectrophoresis or immunofixation and the quantification of immunoglobulins, by radial immunodifussion. Progression to myeloma was defined by: MC > 3 gr/dl, plasma cell infiltration > 10%, or associated lytic bone lesions. Progression to another B-cell neoplasm was considered when there was histologic evidence of the disease. The identification of prognostic factors was made using Cox models. PFS and OS were calculated using the Kaplan Meier method and the curves were compared with the log-rank test. Results: The median (md) age at diagnosis was 62 years (range 24–89 years) and 18% of the pts were younger than 50. Anemia not related to the monoclonal protein was present in 18% of the pts. Albumin, beta 2 microglobulin and erythrocyte sedimentation rate (ESR) were normal in 88%, 50% and 41% of the pts, respectively. MC was 0.6 gr/dl (range 0.1–2.9). In 70% of the cases it was IgG, 15% IgA, 13% IgM and 2% biclonal. The light chain was Kappa in 65% of the pts. Bence Jones was detected in only 9%. Uninvolved immunoglobulins (UI) were reduced in 21% of the pts. Bone marrow analysis were performed in 79 pts (20%) and md plasma cell infiltration was 3 (range 0 – 10). The 387 pts were followed for 2340 person-years (md 4.75 years, range 0 – 31) during which 31 pts (8%) evolved to a malignancy (23 multiple myeloma, 7 NHL, and 1 amyloidosis) and 17 (4.6%) died (3 related to progressive disease, 6 related to non hematological malignancy, 2 associated to cardiovascular disorders, 2 secondary to infection and 4 of unknown cause). PFS and OS at 10 years were 89% and 91%, respectively. The overall risk of progression was 1.3% per year. Among all the variables analysed (age, gender, hemoglobin, albumin, beta 2 microglobulin, ESR, type and concentration of MC, Bence Jones and reduction of UI), only MC concentration (HR 4.81, CI 2.2 – 10.32, p = 0.00007) and ESR (HR 3.67, CI 1.7 – 7.88, p = 0.001) had prognostic value for progression. Conclusions: MC concentration and ESR at diagnosis identified a subgroup of pts with higher risk of transformation in our experience.

scholarly journals Differential diagnosis of monoclonal gammopathy of undetermined significance

Hematology ◽  
2012 ◽  
Vol 2012 (1) ◽  
pp. 595-603 ◽  
Author(s):  
Giampaolo Merlini ◽  
Giovanni Palladini
Keyword(s):  
Differential Diagnosis ◽  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Cell Clone ◽  
Organ Damage ◽  
Organ Injury ◽  
Al Amyloidosis ◽  
Monoclonal Protein ◽  
Undetermined Significance

Abstract Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic plasma cell disorder occurring in 4.2% of adults > 50 years of age, which can progress into symptomatic diseases either through proliferation of the plasma cell clone, giving rise to multiple myeloma and other lymphoplasmacellular neoplasms, or through organ damage caused by the monoclonal protein, as seen in light-chain amyloidosis and related conditions. Differential diagnosis of asymptomatic and symptomatic monoclonal gammopathies is the determinant for starting therapy. The criteria for determining end-organ damage should include markers of organ injury caused by the monoclonal protein. Patient assessment and optimal follow-up are now performed using risk stratification models that should also take into account the risk of developing AL amyloidosis. Patients with low-risk MGUS (approximately 40% of all MGUS patients) need limited assessment and very infrequent follow-up. The ongoing development of novel molecular biomarkers and advanced imaging techniques will improve the identification of high-risk patients who may benefit from early therapeutic intervention through innovative clinical trials.

scholarly journals Follow-up Care of Monoclonal Gammopathy of Undetermined Significance: A Guide for Primary Care Physicians

2021 ◽  
Vol 8 (5) ◽  
Author(s):  
Hammad Z ◽  
◽  
Hernandez E ◽  
Tate S ◽  
◽  
...  
Keyword(s):  
Plasma Cell ◽  
Primary Care Physicians ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Organ Damage ◽  
M Protein ◽  
Bone Lesions ◽  
Al Amyloidosis ◽  
End Organ Damage ◽  
Undetermined Significance

Monoclonal Gammopathy of Undetermined Significance (MGUS) is a condition in which M protein, an abnormal monoclonal immunoglobulin, is present in the blood at a nonmalignant level. Specifically, it is defined by: blood serum M protein concentration <3 g/dL (<30 g/L), <10% plasma cells in the bone marrow, and no evidence of end organ damage [1,2]. Evidence of end organ damage includes hypercalcemia, renal insufficiency, anemia, and bone lesions. These are indicative of MGUS progression and which can be attributed to the monoclonal plasma cell proliferative process [3]. MGUS occurs in 3% of the general population older than 50 years. Incidence increases with age and varies with sex with higher rates observered in males than females [1,4]. MGUS is the most common plasma cell disorder, with 60% of patients that present to the Mayo Clinic with a monoclonal gammopathy being diagnosed with MGUS [3]. While it is typically an asymptomatic condition, it is premalignant disorder to other monoclonal gammopathies. Multiple Myeloma (MM) is almost always preceded by MGUS and the majority of patients will have detectable levels of M protein for at least 5 years prior to MM diagnosis [5,6]. MGUS also precedes immunoglobulin light chain (AL) amyloidosis and Waldenstrom Macroglobulinemia (WM) and tends to progress to disorders at a fixed but unrelenting rate of 1% per year [4].

IgM Multiple Myeloma: Disease Definition, Prognosis, and Differentiation From Waldenstrom's Macroglobulinemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1828-1828 ◽  
Author(s):  
Steven Schuster ◽  
Angela Dispenzieri ◽  
S. Vincent Rajkumar ◽  
Alvaro Moreno Aspitia ◽  
Robert Kyle ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Median Overall Survival ◽  
Bone Lesions ◽  
Lytic Lesions ◽  
Lytic Bone Lesions ◽  
Plasma Cell Disorder ◽  
Definition Of ◽  
Cell Disorder

Abstract Abstract 1828 Poster Board I-854 Background IgM Multiple Myeloma (MM) and Waldenstrom's Macroglobulinemia (WM) are two hematologic diagnoses with the common variable of an IgM monoclonal gammopathy. Distinguishing these two diagnoses is critical as the approach to therapy is different. A study by Avet-Loiseau et al demonstrated the presence of t(11;14) translocations in 7 of 8 patients with IgM MM that was absent in all of a series of 17 cases of WM (Semin Oncol 2003 30:2;153). However, 6 of the 8 IgM MM cases lacked classic lytic lesions. Method A priori, based on the literature and the natural history of MM, we defined IgM MM as a symptomatic clonal plasma cell proliferative disorder characterized by a serum IgM monoclonal protein (regardless of size) plus presence of t(11;14) on fluorescent in situ hybridization (FISH) and/or lytic bone lesions felt to be related to the underlying plasma cell disorder. The cases for the study were screened by a computerized database search for ‘IgM’ and ‘Myeloma’ of all patients seen at Mayo Clinic in the last 30 years at all three sites (Rochester, Arizona and Florida). Patients identified on the computerized screen were then audited by chart review to identify the study cohort. Results 38 cases were identified on initial screen of the computerized database as potential patients with IgM MM. Of these, a total of 22 cases met our specific definition of IgM myeloma (t(11;14 and/or lytic lesions). Of the remaining 16 cases, 8 were IgM MGUS, 5 were WM based on clinical presentation (hyperviscosity, lymphadenopathy and organomegaly) and biopsy findings of lymphoplasmacytic lymphoma, 1 was excluded due to lack of information, and the remaining 2 patients were indeed considered to have clinical IgM MM. Interestingly, these two patients did not have either the t(11;14) or lytic lesions, but rather had immunophenotypic features suggestive of MM and not WM (CD138+, CD20-). Table 1 summarizes the clinical characteristics of the 22 patients who met our criteria for IgM MM. All 22 patients had lytic bone lesions. Of the 17 evaluated with FISH, 6 (35%) demonstrated the t(11;14) abnormality. Median overall survival by Kaplan-Meier analysis was 37 months represented in Figure 1. Conclusion IgM MM is a discrete clinical entity that can and should be distinguished from WM. Our definition of IgM MM is designed to be specific and requires the presence of a symptomatic IgM secreting plasma cell proliferative disorder plus presence of t(11;14) and/or lytic bone lesions felt related to the underlying plasma cell disorder. In this, the largest series of patients with IgM MM, the t(11;14) abnormality is very specific for IgM MM, but may not be sensitive, being present in approximately 1/3 of patients. The median overall survival is similar to non-IgM myeloma patients treated during this period, and much shorter than what would be expected for WM. The minority of symptomatic patients with IgM monoclonal gammopathy who do not meet this criteria, but have immunophenotypic features more suggestive of MM rather than WM need further study. Disclosures No relevant conflicts of interest to declare.

Constitutive gp130-JAK-STAT3 Signaling Induces a Plasma Cell Disorder Representing Genetic and Clinical Features of Human Myeloma – a Novel in Vivo Model for the Patient Subgroup Characterized By a STAT3 Target Gene Signature

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 648-648
Author(s):  
Sabine Steidle ◽  
Tobias Dechow ◽  
Katharina Götze ◽  
Martina Rudelius ◽  
Konstanze Pechloff ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mouse Model ◽  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Bone Lesions ◽  
Activation Pattern ◽  
Stat3 Pathway ◽  
Pathway Activation ◽  
Lytic Bone Lesions

Abstract Multiple myeloma (MM) is a plasma cell neoplasm characterized by the clonal expansion of an immunoglobulin-secreting terminally differentiated B cell. MM patients classically suffer from the triade consisting of plasma cell infiltration of the bone marrow, lytic bone lesions and monoclonal gammopathy in plasma and/or urine. During disease progress patients develop end organ damage such as nephropathy, neuropathy and bone marrow insufficiency. New treatment options including immunomodulatory drugs and proteasome inhibitors have prolonged overall survival and quality of life. However MM is still considered an incurable disease by conventional treatment approaches. Deregulated signal transduction pathways, in particular the Interleukin-6-JAK-STAT3 pathway, play an important role in the growth regulation and survival of MM cells. IL-6 binds to the specific IL-6 receptor and this complex associates with two molecules of the ubiquitously expressed common signal transducer gp130, which leads to JAK-STAT3 activation and STAT3 target expression. Using immunohistochemistry for STAT3 phosphorylation and by assessing gene expression data we have identified a recurrent STAT3 pathway activation pattern in approximately 40% of all MM patients, strongly indicating that deregulated gp130 downstream activation constitutes an attractive therapeutic target in MM. Based on these findings we generated a novel retroviral bone marrow transduction-transplantation MM mouse model using a constitutively active form of gp130, L-gp130. This L-gp130 mouse model shows all characteristics of the human disease, including monoclonal gammopathy, bone marrow infiltration with lytic bone lesions, and protein deposition in the kidney. Essentially, as compared to previous MM models, MM penetrance is very high and tumor latency with a median of approximately 200 days short. The disease is easily transplantable into secondary recipient mice. To assess clonality we subcloned and sequenced IgH rearrangements from individual tumors. Our analyses revealed that diseased mice contained monoclonal and oligoclonal B cell expansions, and also demonstrated a germinal center passage. Fluorescence in situ hybridization revealed the occurrence of Myc aberrations, a genetic feature that is associated with aggressive disease and short survival in human MM. A genetic in vivo approach revealed that gp130 signaling collaborates with Myc to induce MM, and that gp130 signaling is responsible and sufficient for directing the plasma cell phenotype and to dominantly regulate the expression of antiapoptotic proteins. Finally, testing of murine primary MM cells isolated from diseased L-gp130 animals with currently used anti-myeloma drugs such as bortezomib, carfilzomib, melphalan and doxorubicin revealed significant anti-tumor activity. In summary, the L-gp130 MM mouse model provides a novel tool with clinical and genetic features of human MM. It offers several clear advantages over existing murine MM models. Regarding the patient subgroup with a recurrent STAT3 pathway activation pattern it may serve as a genetic and preclinical tool for delineating MM pathogenesis, for evaluation of targeted therapies, and for assessment of in vivo treatment resistance. Disclosures Keller: Cellgene: Research Funding.

Prognostic Factors in Malignant Transformation of Monoclonal Gammopathy of Undetermined Significance

2002 ◽  
Vol 43 (8) ◽  
pp. 1713-1714
Author(s):  
Fausto Adami ◽  
Michela Bortolin ◽  
Maurizio Lestani ◽  
Marco Chilosi ◽  
Gianpietro Semenzato
Keyword(s):  
Prognostic Factors ◽  
Malignant Transformation ◽  
Monoclonal Gammopathy ◽  
Undetermined Significance

Malignant Transformation of Monoclonal Gammopathy of Undetermined Significance: Cumulative Incidence and Prognostic Factors

2001 ◽  
Vol 42 (4) ◽  
pp. 609-618 ◽  
Author(s):  
Niels van deDonk ◽  
Okke de Weerdt ◽  
Marijke Eurelings ◽  
Andries Bloem ◽  
Henk Lokhorst
Keyword(s):  
Prognostic Factors ◽  
Malignant Transformation ◽  
Cumulative Incidence ◽  
Monoclonal Gammopathy ◽  
Undetermined Significance

Serum ß2-Microglobulin lin Patients with Monoclonal Gammopathies

1987 ◽  
Vol 2 (3) ◽  
pp. 169-172 ◽  
Author(s):  
Samuele Di Giovanni ◽  
Gaetano Valentini ◽  
Emma Ravazzolo ◽  
Paolo Carducci ◽  
Paolo Giallonardo ◽  
...  
Keyword(s):  
Monoclonal Gammopathy ◽  
Serum Samples ◽  
Monoclonal Protein ◽  
Β2 Microglobulin ◽  
Monoclonal Gammopathies ◽  
Protein Levels ◽  
Neoplastic Process ◽  
The Mean ◽  
Beta 2 Microglobulin ◽  
Undetermined Significance

Beta-2-microglobulin concentrations were determined in serum samples from 45 patients with benign and malignant monoclonal gammopathies. In the group of patients suffering from multiple myeloma or Waldenström macroglobulinemia the mean β2-microglobulin level was significantly higher than in the group with monoclonal gammopathy of undetermined significance. Values above 3 mg/L were highly indicative of a neoplastic process and were observed in all the Waldenström patients and in > 90% of myeloma patients. No significant correlation was noticed between β2-microglobulin and monoclonal protein levels in any of the groups examined.

A Long-Term Study of Prognosis on Monoclonal Gammopathy of Undetermined Significance.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4994-4994
Author(s):  
Delvyn Caedren Case ◽  
Marjorie A. Boyd
Keyword(s):  
Bone Marrow ◽  
Disease Progression ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Lymphocytic Leukemia ◽  
Bone Lesions ◽  
Monoclonal Protein ◽  
Long Term Study ◽  
Progression Of Disease ◽  
Undetermined Significance

Abstract From 1976 to 2006, 547 patients have been identified and followed for monoclonal gammopathy of undetermined significance (MGUS). Criteria of inclusion included presence of serum monoclonal protein of a concentration of 2 g per deciliter or less; no or moderate amounts of monoclonal light chains in the urine; the absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the monoclonal protein; and proportion of plasma cells in the bone marrow of 5% or less. Patients identified as MGUS were followed every 6 months with physical examination, CBC, chemistries, and paraprotein studies. Ages ranged from 32 – 100 years (median 70 years). There were 214 males and 333 females. Over the 30 years of observation, 61 patients have developed disease progression: myeloma 29, lymphoma 12, macroglobulinemia 10, chronic lymphocytic leukemia 7, and amyloid 3. Time to develop myeloma ranged from 2–24 years (median 6 years), macroglobulinemia 2–8 years (median 5 years), and amyloid 3–10 years (median 10 years). Patients developed myeloma throughout the entire period of observation: 2, 3, 3, 4, 4, 4, 4, 5, 5, 5, 6, 6, 6, 6, 6, 7, 7, 8, 8, 9, 10, 10, 11, 14, 15, 15, 18, 20, and 24 years. Survival from diagnosis of myeloma was 1+ – 14+ months (median 36 months) for myeloma and 24 – 108+ months (median 48 months) for macroglobulinemia. The only reliable method of identifying progression of disease to myeloma/macroglobulinemia/amyloid was serial determinations of paraprotein level. In this large series followed for 30 years, with a more restricted diagnosis of MGUS (paraprotein level ≤ 2 g per deciliter and 5% or less bone marrow plasma cells), 1% of all patients identified developed progression of disease. No patient developed disease progression in less than 2 years using the more restricted diagnosis. Risk of progression increased with time with patients developing myeloma even 20 years or longer of follow-up. Serial evaluations of paraprotein levels are indicated in patients identified as MGUS.

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