Acromegaly associated with monoclonal gammopathy of undetermined significance (MGUS)

Here we report the case of a 65-year-old woman with acromegaly complicated with monoclonal gammopathy of undetermined significance (MGUS). The patient visited Shimane University Hospital for treatment of spinal canal stenosis, and was diagnosed as acromegaly with GH 43.1 ng/ml, insulin-like growth factor (IGF)-I 510 ng/ml and the detection of a pituitary adenoma by MRI. She was also diagnosed as MGUS with IgG 2208 mg/dl, the existence of IgG-kappa type monoclonal protein, and 5.6% plasma cells in bone marrow. After a pituitary adenoma was operatively removed by transsphenoidal approach, IgG levels, as well as GH and IGF-I levels, decreased spontaneously and simultaneously. We suspect a pathogenetic link between acromegaly and MGUS in this case, because both GH and IGF-I are known to directly promote immunoglobulin production from plasma cells, thus inducing the proliferation of the cells in vitro.     

Incidence and evolution of monoclonal gammopathy of undetermined significance (MGUS) in Greece

Monoclonal gammopathy of undetermined significance (MGUS) is a relatively common condition among individuals older than 70 years. The actuarial risk of MGUS progression to an overt plasma cell malignancy (PCM) after 20 years of follow-up has been reported to be as high as 30%. The purpose of this study was to evaluate the incidence and evolution of MGUS in a Greek population: 1564 consecutive patients older than 50 years who were admitted to the Department of Clinical Therapeutics at the University of Athens School of Medicine for various reasons over a 26-month period were evaluated with serum protein electrophoresis. In cases in which a monoclonal protein was detected, a panel of tests was performed to rule out an underlying plasma cell malignancy (PCM). Serum levels of interleukin (IL)-6, IL-6-soluble receptor (IL-6SR), IL-1 beta, and transforming growth factor beta 1 were also measured in the MGUS cases. Patients with MGUS were monitored at regular intervals for evidence of multiple myeloma or other PCMs. The incidence of MGUS was 4% and there was a positive correlation with increasing age. The median value of serum M peak was only 5.3 g/l. After a median follow-up of 71 months, only two patients developed multiple myeloma (60 and 75 months after initial diagnosis). Our data are consistent with those of other epidemiological studies regarding the incidence of MGUS, but the monoclonal protein levels and the probability of evolution to a malignant plasma cell disorder appeared to be lower in our study than in other series. Our data support the hypothesis that individuals with low M peak values require only regular annual follow-up examinations.     

The incidental monoclonal protein: Current approach to management of monoclonal gammopathy of undetermined significance (MGUS)

‘Monoclonal gammopathy of undetermined significance’ (MGUS) is a pre-malignant disorder characterized by limited clonal proliferation of the bone marrow plasma cells without any evidence of end-organ damage. A better understanding of the prevalence rates, natural history, and the risk factors for progression of MGUS, provides further insight into the clinical approach to management of this condition. The clinical implications of MGUS such as the risk of fracture, miscellaneous conditions associated with a monoclonal M-protein, and a practical approach to the management of MGUS patients based on a risk-stratification model are discussed in this review.     

Prevalence and progression of monoclonal gammopathy of undetermined significance and light-chain MGUS in Germany

We determined the prevalence and progression rate of monoclonal gammopathy of undetermined significance (MGUS) and light-chain MGUS (LCMGUS) in Germany utilizing the biobank of the population-based Heinz Nixdorf Recall Study. The Heinz Nixdorf Recall Study comprises 4,814 men and women aged 45-75?years. To detect monoclonal proteins, standard serum electrophoresis was combined with parallel screening immunofixation using pentavalent antisera. Additionally, free light chains (FLC) were measured in all samples. Definition of MGUS included M-protein concentration, laboratory results, and disease history. LCMGUS was defined as abnormal FLC ratio, increase in FLC causing the abnormal ratio, and lack of intact immunoglobulin. One hundred sixty-five MGUS cases were identified among 4,702 screened samples (prevalence 3.5%, 95% confidence interval (CI) 3.0-4.1; median age 63?years, range 47-75?years; 103 (62%) male; IgG 59%, IgA 17%, IgM 17%, biclonal 4.8%, kappa 56%, and lambda 44%). Five cases progressed (0.6%/year, 95% CI 0.2-1.4). An abnormal FLC ratio was detected in 220 samples. Thirty-nine of these showed intact immunoglobulin. Thirty-four of the remaining met LCMGUS criteria (prevalence 0.7%, 95% CI 0.5-1.0). None of the LCMGUS cases progressed. We demonstrate a MGUS prevalence of 3.5% and a LCMGUS prevalence of 0.7% in the general population aged 45-75?years in Germany using a sensitive screening approach.     

Monoclonal gammopathy of undetermined significance in systemic transthyretin amyloidosis (ATTR)

Objective: To identify the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in patients with transthyretin (ATTR) amyloidosis.

Patients and methods: We performed a retrospective analysis of patients with biopsy-proven ATTRwt (wild-type transthyretin amyloid protein) and genopositive ATTR V122I (valine-to-isoleucine substitution at position 122 of the TTR gene) amyloidosis evaluated at the Amyloidosis Center at Boston University and Boston Medical Center between 1 January 2003 and 31 December 2016.

Results: There were a total of 226 patients with ATTRwt and ATTR V122I amyloidosis evaluated during the specified time frame with 155 and 71 patients in each cohort, respectively. Those with complete medical records, 140 patients with ATTRwt and 57 V1221 ATTRm subjects, were included in the analyses. Fifty-five patients (39%) in the ATTRwt cohort and 28 patients (49%) in the ATTR V122I cohort had an MGUS, as indicated by an abnormality in the serum-free light-chain ratio and/or serum immunofixation electrophoresis.

Conclusion: These data confirm the high prevalence of coexistent MGUS with ATTR amyloidosis in this patient population, with an MGUS rate that is higher than the general population. These findings also highlight the importance of a thorough diagnostic evaluation in patients with amyloidosis to determine the precursor protein, as the clinical course and treatment of AL (light-chain amyloid protein) and ATTR amyloidosis are distinct.     

The significance of monoclonal gammopathy of undetermined significance

Since it is now well established that all patients with multiple myeloma have a preceding monoclonal gammopathy of undetermined significance (MGUS), identification of potential risk factors for the progression becomes most important. In this perspective article, Drs. Kyle and Kumar highlight the need for a better understanding of the etiology and biology of MGUS. See related paper on page 1714.Monoclonal gammopathy of undetermined significance (MGUS) is characterized by a serum M protein concentration of less than 30 g/L, fewer than 10% clonal plasma cells in the bone marrow, and the absence of end-organ damage that can be attributed to the plasma cell proliferative disorder. End-organ damage is defined by hypercalcemia, renal insufficiency, anemia, or bone lesions (CRAB) related to the plasma cell proliferative disease.¹The prevalence of MGUS was 3.2% in 21,463 predominantly white residents of Olmsted County, Minnesota, who were 50 years of age or older.² The prevalence was 4.0% in men and 2.7% in women, 5.3% in persons 70 years of age or older, and almost 9% in men older than 85 years of age. Despite the common occurrence of MGUS, it is markedly underdiagnosed in the general population because this condition is asymptomatic and does not produce the signs or symptoms of multiple myeloma or related disorders. We found that the prevalence of MGUS in Olmsted County was 3.8% in persons 70 years of age, but that the prevalence of clinically detected cases at this age was only 0.8%. Thus, only 21% of patients with MGUS at the age of 70 were detected by clinical practice in Olmsted County.³ In contrast, at the age of 80, 33% of patients with MGUS were detected by routine clinical practice, while the clinical detection rate was only 8% in those 50 years old. Overall, only 22% of patients with a known MGUS were recognized by routine clinical practice in Olmsted County, Minnesota.The prevalence of MGUS in African Americans^{4, 5} and Africans⁶ is approximately double that in whites. The prevalence in Japan is lower than in whites.⁷The cause of MGUS is not known. In a report of atomic bomb survivors, those exposed to high levels of radiation at a young age had an increased risk of MGUS. Pesticides have also been implicated. In a study of pesticide applicators living in Iowa or North Carolina, the age-adjusted prevalence of MGUS was 1.9-fold higher than in men from Minnesota.⁸ A 3-fold or greater risk was found in users of dieldrin, a chlorinated insecticide and the carbon-tetrachloride-carbon disulfide fumigant mixture. There was also an increased risk of MGUS in those exposed to the fungicide chlorthalonil. There is also a genetic element. A report on 247 first-degree relatives of 97 MGUS patients showed an approximate 2-fold higher risk of MGUS in first-degree relatives.⁹What is the importance of MGUS? Is it simply an interesting laboratory finding or is it of importance to the patient? Prior to 1978, the presence of an asymptomatic M protein was often referred to as benign monoclonal gammopathy. In that year, we published the findings of a study of 241 patients with a monoclonal gammopathy but no evidence of multiple myeloma, Waldenström’s macroglobulinemia, AL amyloidosis or a lymphoproliferative disorder. In our study, we coined the term monoclonal gammopathy of undetermined significance (MGUS) to describe such patients because multiple myeloma or a closely related plasma cell disorder developed at a rate of 1.5% per year, indicating that the condition was not entirely benign.¹⁰ This cohort was followed up for 3,579 person-years of observation. Sixty-four patients (27%) developed multiple myeloma or a related disorder. The interval from the recognition of MGUS to diagnosis of multiple myeloma or a related disorder ranged from 1 to 32 years (median 10.4 years). The risk of progression, which was 1.5% per year, was still continuing without change after 25 years of observation.¹¹In order to confirm the findings of the 241 Mayo Clinic patients from the USA and other countries which may be subject to referral bias, we conducted a study of 1,384 patients with MGUS from the 11 counties of Southeastern Minnesota evaluated at the Mayo Clinic from 1960 to 1994.¹² The median age at diagnosis was 72 years, which is 8 years older than that of the original cohort of 241 patients. During a follow-up of 11,009 person-years (median 15.4 years; range, 0 to 35 years), 70% died, indicating a mature follow-up. Multiple myeloma, AL amyloidosis, lymphoma with an IgM serum protein, Waldenström’s macroglobulinemia, plasmacytoma or chronic lymphocytic leukemia developed in 115 patients (8%). The cumulative probability of progression was 10% at 10 years, 21% at 20 years, and 26% at 25 years. Thus, the risk of progression was approximately 1% per year. These patients were at risk of progression, even after more than 25 years of follow-up. The number of patients with progression to a plasma cell disorder (n=115) was 7.3 times the number expected. The risk of developing multiple myeloma was increased 25-fold, that of developing Waldenström’s macroglobulinemia 46-fold, and that of AL amyloidosis 8.4-fold. The risk of lymphoma was moderately increased at 2.4-fold, but this risk was underestimated because only lymphomas associated with an IgM protein were counted in the observed number, while the incidence rates for lymphomas associated with IgG, IgA, and IgM proteins were used to calculate the expected number. Multiple myeloma accounted for 75 of the 115 cases (65%) of progression to a malignant plasma cell disorder. The characteristics of these 75 patients who developed multiple myeloma following the presence of MGUS were comparable with those of the 1,027 patients with newly-diagnosed multiple myeloma who were referred to the Mayo Clinic between 1985 and 1988, except that the Southeastern Minnesota population was older (median 72 years vs. 66 years) and the percentage of men was lower (45% vs. 60%).¹³ This study confirmed that MGUS is indeed an important disorder, in which the risk of progression to malignancy persists indefinitely.The finding that MGUS predisposes to multiple myeloma raises the question of whether multiple myeloma is always preceded by a MGUS or whether the disease can arise de novo. In clinical practice, data from the Mayo Clinic series of 1,027 consecutive patients with multiple myeloma suggest that only 20% of these patients had a known prior diagnosis of MGUS. We had the opportunity of utilizing the USA PLCO (prostate, lung, colorectal, and ovarian) Cancer Screening Trial to address this question. In this study of 77,469 people who were cancer-free, we identified 71 individuals who subsequently developed multiple myeloma during the study in which serially collected serum samples were obtained from 2 years to 9.8 years prior to the diagnosis of the myeloma. The median age of these 71 patients was 70 years and 71.4% were male. MGUS was present in 100% of patients 2 years prior to the diagnosis of multiple myeloma. At 5 years prior to the diagnosis of multiple myeloma, 95% had MGUS while at 8 or more years prior to the diagnosis of multiple myeloma, 82.4% had a preceding MGUS.¹⁴ The median size of the M protein increased from 0.9 g/dL at 8+ years to 1.6 g/dL at 2 years prior to the diagnosis of multiple myeloma. Approximately one-half of the myeloma patients had a year-by-year increase in M protein until the diagnosis of multiple myeloma. The type of M protein was IgG (68%), IgA (21.5%), IgM (1.5%), or biclonal (3%), and 4.7% had light chain MGUS. Thus, this study established that virtually all patients with multiple myeloma have a preceding MGUS. These findings were confirmed by another study in which 27 of 30 patients with multiple myeloma had a preceding monoclonal protein. Three patients had no evidence of an M protein; one had only one prediagnostic sample available 9.5 years before the diagnosis of multiple myeloma, while the other two patients had IgD myeloma and their most recent prediagnostic samples were 5.3 and 3.3 years prior to the diagnosis of myeloma.¹⁵In this issue of the journal, Kristinsson and colleagues describe an important study determining the mortality patterns and causes of death in MGUS patients in comparison to controls.¹⁶ They identified a nation-wide cohort of 4,259 MGUS patients diagnosed from 1986 to 2005 and compared them to 16,151 matched controls. They demonstrated excess mortality in patients with MGUS. The excess mortality increased with longer follow-up. Younger patients with MGUS had a significantly lower excess mortality rate compared to that of older patients. MGUS patients had an increased risk of dying from multiple myeloma, Waldenström’s macroglobulinemia, other lymphoproliferative malignancies, other hematologic malignancies, amyloidosis, bacterial infections, ischemic heart disease, other heart disease, other hematologic conditions, liver disease, and renal disease. The major shortcoming of this study is that since MGUS was diagnosed clinically, the causes of death besides plasma cell disorders are likely affected by the reason the patient underwent electrophoresis rather than the presence or absence of MGUS detected on that test. This bias can be overcome only if a study is undertaken on a population-wide basis, or if the deaths in patients who were tested and found negative for MGUS can be used as the control group.Nevertheless, we have also found a shorter survival in MGUS patients when compared to the age- and sex-matched normal population. In our report of 241 patients with MGUS, the median survival was 13.7 years, compared to 15.5 years for the USA population using 1930 to 2000 decennial life tables (Figure 1). Each patient was matched to the control population by age, sex, and date of entry.¹¹ The median survival of our 1,384 patients from Southeastern Minnesota was 8.1 years, compared to the 11.8 years expected for Minnesota residents of matched age and sex¹⁷ (Figure 2). Van de Poel et al. reported that the long-term survival of 334 patients with MGUS was slightly shorter than the expected survival of age- and sex-adjusted controls.¹⁸ Survival of patients with MGUS has also been reported in cohorts from the Netherlands¹⁹ and from Denmark.²⁰ Kristinsson et al. have confirmed these findings in their article in this issue of the journal and have extended this work by comparing the causes of death with those of the matched controls.¹⁶Open in a separate windowFigure 1.Survival rate of 241 patients with monoclonal gammopathy of undetermined significance compared with expected survival rate of the USA population using 1930–2000 decennial life tables. Reproduced from Kyle et al.¹¹Open in a separate windowFigure 2.Survival of 1384 patients with monoclonal gammopathy of undetermined significance from South-Eastern Minnesota compared with a normal population (8.1 vs.11.8 years, respectively) ( p <0.001). Reproduced from Kyle et al.¹⁷The goal of our overall efforts is to identify patients with MGUS who are at the highest risk of progression to multiple myeloma or another disorder. The next step is to treat these MGUS patients in an effort to reduce or prevent the development of multiple myeloma. Demonstration of a treatment capable of delaying or preventing progression requires a controlled clinical trial with a placebo comparator arm which shows a low toxicity profile, no impact on quality of life, and an improvement in overall survival. The use of current agents outside the context of clinical trials is not recommended because of the unknown ratio between potential benefit and toxicity. At present, no current agents are recommended for clinical use in MGUS.²¹The benign monoclonal gammopathy patient of the past has been shown to be an important element in unlocking the mysteries of the plasma cell dyscrasias – particularly multiple myeloma. It is well accepted that MGUS patients have an excess risk of developing multiple myeloma and related plasma cell disorders. It has recently been demonstrated that virtually all patients with multiple myeloma have a preceding MGUS.^14,15We first need to try and understand the etiology and biology of MGUS better. Why do blacks have a higher risk of progression than whites? Is the reason for the racial disparity genetic or environmental? What other factors may play a role? It is apparent that genetic factors may predispose patients to develop MGUS and ultimately multiple myeloma or a related disorder. For example, Vachon et al. demonstrated a 2-fold greater risk of MGUS in first-degree relatives of MGUS patients when compared with the control population.⁹ We now need to try and identify specific genes that may be involved in familial predisposition to developing MGUS. Environmental risk factors also need to be studied. It has been shown that exposure to radiation at an early age results in an increased frequency of MGUS ⁷ and that farmers and agricultural workers also have an elevated risk of multiple myeloma.²² Insecticides, herbicides, and fungicides have all been hypothesized as potential causes in this population. It has also recently been reported that a cohort of males exposed to insecticides from North Carolina and Iowa have a 2-fold increased rate of MGUS when compared to an age-adjusted population from Southeastern Minnesota.Second, there are likely many different cytogenetic categories of MGUS that need to be studied in detail, to determine, for instance, whether progression to myeloma is more rapid in those with translocations such as t(4;14).The fact that all patients with multiple myeloma have a preceding MGUS makes it imperative that we identify potential risk factors responsible for the progression of MGUS to a serious plasma cell dyscrasia. Since only a small number of patients with MGUS progress on an annual basis, the number of subjects needed for a preventive strategy is large. Preventive studies therefore need to target those at the highest risk of progression. Definitive studies to prevent progression in high-risk patients will be feasible in the future, but since MGUS is asymptomatic, safety is an important issue in these trials. We believe that demonstration of a treatment capable of delaying progression requires a controlled clinical trial with a placebo comparator arm and such a trial must show that the treatment improves overall survival, preserves quality of life, and has a low toxicity. Treatment of MGUS outside the context of a clinical trial is not recommended because of the uncertain ratio between potential benefit and toxicity. Future studies should refine the risk factors for progression and develop criteria to identify people at high risk of progression who are candidates for preventive trials, as well as identify patients without any risk of progression who can be reassured.     

Blood clonal B-cell excess in patients with monoclonal gammopathy of undetermined significance (MGUS): association with malignant transformation

Fifty-seven patients with monoclonal gammopathy of undetermined significance (MGUS) were analysed for the presence of blood clonal B-cell excess (CBE), defined as a lymphocyte surface membrane κ/λ light chain ratio outside the normal range (> 3.5 in κ-type MGUS and <0.9 in λ-type MGUS). 15 patients (26%) had a CBE. The patients were followed for a median time of 8.4 years (range 0.5–20.2). Eight of the 15 CBE⁺ MGUS patients (53%) developed a B-cell malignancy as compared to 7/42 patients (17%) in the CBE group and the difference in event-free (malignancy-free) observation time was statistically significant (P = 0.01). Cox's regression analysis showed that the presence of CBE was the most powerful predictor of progression to a malignant disease. Two patients with a normal κ/λ ratio at first test were analysed repeatedly during follow-up. Subsequently, a CBE appeared which gradually increased in size preceding the clinical diagnosis of a malignant disease.     

Blood clonal B-cell excess in patients with monoclonal gammopathy of undetermined significance (MGUS): association with malignant transformation

A Leu– Pro substitution at position 129 of the ci globin gene was detected in three members of a Tunisian family by sequencing the whole a₂ and i DNA. The mutation was verified by dot-blot allele-specific hybridization as well as by digestion of PCR and RT-PCR products with Nci I, since the aj^{129 T_>c} mutation creates an additional recognition site for the above-mentioned enzyme. The Q,_ii29(Hi2)Leup_{ro substitution} disturbs helix H resulting in a-thal trait most probably because the unstable a-globin chain variant cannot form a/3 dimers. A search for the abnormal Hb and for the abnormal a globin chain by isoelectric focusing, carboxymethyl cellulose chromatography and electrospray ionization mass spectrometry was negative. In the heterozygous state, the _Qii29(Hi2) Leu-Pro _varj_{ant is man}if_est_ed by microcytosis (MCV73fl), whereas in the homozygous state there is moderate anaemia with marked microcytosis (Hb 11–6 g/dl, MCV 65 fl).     

Prognosis in monoclonal gammopathy of undetermined significance

Eighty-seven patients with monoclonal gammopathy of undetermined significance (MGUS) were followed for a period of 1–20 years, median 91 months. Transformation to multiple myeloma occurred in 14 patients of whom seven died as a consequence of the disease. There were 13 unrelated deaths. The actuarial probability of survival was 80% at 10 years and 44% at 15 years and the probabilities of malignant conversion for the same periods were 17% and 30% respectively. The most significant factor influencing the probability of malignant conversion was the increase of monoclonal protein above the level of 30 g/l during the observation period ( P <0.001), followed by an increase of M-protein to more than 50% above the baseline level ( P =0.02) and a decreased level of uninvolved immunoglobulins ( P =0.054).     

Soluble CD16 (sCD16), a marker of malignancy in individuals with monoclonal gammopathy of undetermined significance (MGUS)

There are no well-defined host markers to determine which patients with a diagnosis of monoclonal gammopathy of undetermined significance (MGUS) will progress to multiple myeloma (MM). In this preliminary study we measured plasmatic soluble Fcγ receptor type III (sFcγRIII or sCD16) in 54 individuals with MGUS, 35 patients with multiple myeloma (MM) and 29 healthy controls. We confirmed, through receiver operating characteristic (ROC) curve analysis, that a low level of sCD16 discriminates MM patients from controls. Indeed, for a sCD16 value of 1.3 μg/ml, the sensitivity, as well as the specificity, of this discrimination were both equal to 83%, i.e. 83% of MM patients had a plasmatic sCD16 value <1.3 μg/ml compared with only 17% of controls. Moreover, ROC curve analysis showed that a low sCD16 level also identifies among MGUS patients a subgroup of patients who rapidly progress towards multiple myeloma: in this comparison, for a sCD16 level of 1.3 μg/ml, sensitivity and specificity were 70% and 79% respectively. Therefore a low sCD16 level in MGUS indicated a high likelihood of rapid evolution to MM. In contrast to sCD16, soluble IL-6R did not appear to be discriminant in this study.     

Monoclonal gammopathy of undetermined significance (MGUS) in patients with solid tumors: effects of chemotherapy on the monoclonal protein

The aim of this study was to assess the effect of systemic chemotherapy on the monoclonal protein levels of patients with solid tumors who also have a monoclonal gammopathy of undetermined significance (MGUS). All patients with solid tumors who were referred to our department for consideration of systemic chemotherapy were evaluated with serum protein electrophoresis (SPEP) for the presence of MGUS. When MGUS was confirmed with immunofixation, serial SPEP was performed during and after completion of chemotherapy. Over a 6-year period, 21 patients with solid tumors and MGUS were prospectively identified and assessed. At least 50% reduction of serum monoclonal protein was noted in 4 of 11 patients treated with paclitaxel or docetaxel with a platinum analogue and in 5 of 7 patients who received an irinotecan-containing regimen. Our data indicate that in MGUS patients treated with irinotecan-containing chemotherapy regimens, a high incidence of reduction in their monoclonal protein levels is observed. Since topotecan, another topoisomerase I inhibitor, has some activity in multiple myeloma, further evaluation of irinotecan may be warranted. Evaluation of larger numbers of MGUS patients treated with chemotherapy for their underlying malignancy may help identify in vivo potentially active agents and regimens for patients with overt myeloma.     

Prognostic factors in monoclonal gammopathy of undetermined significance

A retrospective evaluation of 285 patients with monoclonal gammopathy of undetermined significance was performed to identify variables associated with progression, actuarial progression free survival (PFS) and overall survival (OS). Three variables, level of uninvolved immunoglobulins (HR 4.98, CI95% 2 -12.4, p=0.0006), monoclonal protein concentration (HR 4.04, CI95% 1.6-10.34, p=0.004), and erythrosedimentation rate (HR 3.94, CI95% 1.33-11.6, p=0.01), showed independent prognostic significance. With a median follow-up of 66 months (range 6-378), PFS and OS at 10 years were 89% and 91% respectively.     

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意义未明单克隆免疫球蛋白血症(monoclonal gammopathy of undetermined significance,MGUS)指血清中出现单克隆免疫球蛋白,但缺乏浆细胞病或其他相关疾病,如Waldenstr(o)ms巨球蛋白血症(WM)、原发性淀粉样变(AL)、B细胞淋巴瘤(B-NHL)、慢性白血病(CLL)的证据和特征.曾一度被称作为"良性单克隆免疫球蛋白病(benign monoclonal gammopathy,BMG)",后证实一部分病例可发展演变为恶性疾病,故以MGUS命名之.