Objective: To analyze the clinical presentation and progression risk factors of patients with monoclonal gammopathy of undetermined significance (MGUS) in China. Methods: We retrospectively assessed the clinical features and disease progression of 1 037 patients with monoclonal gammopathy of undetermined significance between January 2004 and January 2022 at Peking Union Medical College Hospital. Results: A total of 1 037 patients were recruited in the study, including 636 males (63.6%) , with a median age of 58 (18-94) years. The median concentration of serum monoclonal protein was 2.7 (0-29.4) g/L. The monoclonal immunoglobulin type was IgG in 380 patients (59.7%) , IgA in 143 patients (22.5%) , IgM in 103 patients (16.2%) , IgD in 4 patients (0.6%) , and light chain in 6 patients (0.9%) . 171 patients (31.9%) had an abnormal serum-free light chain ratio (sFLCr) . According to the Mayo Clinic model for risk of progression, the proportion of patients in the low-risk, medium-low-risk, medium-high risk, and high-risk groups were 254 (59.5%) , 126 (29.5%) , 43 (10.1%) , and 4 (0.9%) , respectively. With a median follow-up of 47 (1-204) months, 34 of 795 patients (4.3%) had disease progression, and 22 (2.8%) died. The overall progression rate was 1.06 (0.99-1.13) /100 person-years. Patients with non-IgM MGUS have a markedly higher disease progression rate per 100 person-years than IgM-MGUS (2.87/100 person-years vs 0.99/100 person-years, P=0.002) . The disease progression rate per 100 person-years in non-IgM-MGUS patients of Mayo classification low-risk, medium-low risk and medium-high risk groups were 0.32 (0.25-0.39) /100 person-years, 1.82 (1.55-2.09) /100 person-years, and2.71 (1.93-3.49) /100 person-years, which had statistically difference (P=0.005) . Conclusion: In comparison to non-IgM-MGUS, IgM-MGUS has a greater risk of disease progression. The Mayo Clinic progression risk model applies to non-IgM-MGUS patients in China.
Male ; Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Monoclonal Gammopathy of Undetermined Significance ; Retrospective Studies ; Risk Factors ; Immunoglobulin Light Chains ; Disease Progression

Humans ; Paraproteinemias ; Monoclonal Gammopathy of Undetermined Significance ; Kidney ; Mass Spectrometry

OBJECTIVE: To summarize and compare the clinical baseline characteristics of patients with monoclonal gammopathy of undetermined significance (MGUS), primary light chain amyloidosis (pAL), multiple myeloma (MM), or MM with concurrent amyloidosis, especially the differences in cytogenetic abnormalities. METHODS: The clinical data of 15 cases of MGUS, 34 cases of pAL, 842 cases of MM and 23 cases of MM with concurrent amyloidosis were analyzed and compared retrospectively. RESULTS: Cytogenetic statistics showed that the incidence of t (11; 14) in the four groups (MGUS vs pAL vs MM vs MM with concurrent amyloidosis) was 0%, 33.3%, 16.4%, and 15.8%, respectively (P=0.037); that of 13q deletion was 20.0%, 14.7%, 45.8% and 56.5%, respectively (P<0.001); gain of 1q21 was 50.0%, 12.5%, 47.4% and 40.9%, respectively (P=0.001). Proportion of pAL patients with 0, 1 and≥2 cytogenetic abnormalities (including 13q deletion, 17p deletion, 1q21 amplification and IgH translocation) accounted for 41.9%, 41.9% and 16.1%, respectively; while the proportion of the same category in MM was 17.6%, 27.3%, and 55.2% respectively; this ratio of MM with concurrent amyloidosis was more similar to MM. Subgroup analysis showed that genetic abnormalities (including 13q deletion, 17p deletion and 1q21 amplification) were comparable within t (11; 14) negative and positive groups. Compared with positive cases, t(11; 14) negative patients with MM or MGUS were more likely to have 13q deletions and multiple genetic abnormalities. CONCLUSION Clinical characteristics of pAL, especially cytogenetic abnormalities, are significantly different from MM with concurrent amyloidosis. It suggests that although the onset characteristics are similar, actually the two diseases belong to different disease subtypes which should be carefully predicted and identified.
Amyloidosis ; Humans ; In Situ Hybridization, Fluorescence ; Monoclonal Gammopathy of Undetermined Significance/complications* ; Multiple Myeloma ; Retrospective Studies

OBJECTIVE: To study the distribution of monoclonal gammopathy of undetermined significance(MGUS) in different age, sex and ethnic people over 40 years old. METHODS: Five hundred and ninety-six people(over 40 years old) examened in the Health Examination center of the First Affiliated Hospital of Xinjiang Medical University from July 2017 to September 2017 were selected. Among 596 people, male 310, female 286, Han people 488, and Uygur ethnic people 108. According to age, 596 people were divided into 3 groups, (40-59 years old group, 60-79 years old group, over 80 years old group). First, all samples were screened by capillary serum protein electrophoresis. If the suspected monoclonal bands were found in the electrophoretogram, and then the specific protein types were determined by serum immunofixation electrophoresis. RESULTS: The total incidence of MGUS in 596 screened population was 4.027%. The incidence of MGUS in 40-59 years old group, 60-69 years old group and over 80 years old group were 1.762%, 2.929% and 10% respectively, and the differences among the groups were statistically significant(P<0.05). The incidence of MGUS in male (5.806%) was significantly higher than that in female (2.097%)(χ=5.177，P<0.05). Binary Logistic regression analysis showed that over 80 years old and male were independent risk factors for MGUS(P=0.001, OR=4.188, 95%CI: 1.814-9.673, P=0.048, OR=2.605, 95%CI: 1.009-6.725). The types of immunoglobulin in patients with MGUS were mostly IgG, IgG(66.7%) was significantly more than IgA (29.2%)(χ=21.375，P<0.05)，and there was no significant difference in the incidence of MGUS between people with in Kappa and Lambda. CONCLUSION The age increase and male may increase the incidence of MGUS, the IgG is the most common type of immunoglobcdin in pathogenesis of MGUS, so the early screening should be done.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Immunoglobulins ; Incidence ; Male ; Middle Aged ; Monoclonal Gammopathy of Undetermined Significance ; Paraproteinemias ; Risk Factors

Swallowing can be affected by a variety of systemic diseases. The etiology of dysphagia in the geriatric population is usually overlooked due mainly to a presumed diagnosis of presbyphagia or difficulty in revealing the direct cause. On the other hand, dysphagia can be a meaningful clinical sign of premalignant systemic disease. A 78-year-old man, without any prior medical or family history, was admitted with the chief complaint of dysphagia with recent aspiration pneumonia. Instrumental swallowing tests revealed a severe degree of dysphagia due to decreased laryngopharyngeal sensation and weakness of the pharyngeal constrictor muscles. Extensive workup, including electromyography and laboratory tests, revealed severe sensorimotor peripheral polyneuropathy related to monoclonal gammopathy. Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant precursor of multiple myeloma, which is characterized by the proliferation of monoclonal proteins. These conditions are often associated with peripheral polyneuropathy, ataxia, and sometimes even muscle weakness. Although dysphagia can occur in other systemic disorders, such as vasculitis or paraneoplastic syndrome-related malignancies, there are few reports of dysphagia related to MGUS. The patient was followed up for three years. The MGUS showed no further progression, but the patient showed no improvement, indicating a protracted clinical course and poor prognosis when dysphagia is related to MGUS.
Aged ; Ataxia ; Deglutition ; Deglutition Disorders ; Diagnosis ; Electromyography ; Hand ; Humans ; Monoclonal Gammopathy of Undetermined Significance ; Multiple Myeloma ; Muscle Weakness ; Muscles ; Paraproteinemias ; Pneumonia, Aspiration ; Polyneuropathies ; Prognosis ; Sensation ; Vasculitis

Anemia ; Humans ; Male ; Middle Aged ; Monoclonal Gammopathy of Undetermined Significance ; Paraproteinemias

Although neutrophilia can manifest from various causes, it is important to be able to distinguish chronic neutrophilic leukemia (CNL) from neutrophilic leukemoid reactions (NLR). In this paper, we describe four cases of leukocytosis with neutrophilia, including one case of CNL with a T618I mutation in colony stimulating factor 3 receptor (CSF3R) and three cases of NLR associated with malignancy or sepsis, which were initially suspected as CNL. Of the three NLR cases, one was associated with ovarian cancer, one with monoclonal gammopathy of undetermined significance and one with multiple myeloma with sepsis. This study demonstrated that confirming the clonality of myeloid cells with CSF3R T618I could contribute to making an accurate differential diagnosis between CNL and NLR in patients with solid cancers or plasma cell neoplasms caused by paraneoplastic syndromes and/or infection.
Colony-Stimulating Factors ; Diagnosis, Differential ; Humans ; Leukemia, Neutrophilic, Chronic* ; Leukemoid Reaction* ; Leukocytosis ; Monoclonal Gammopathy of Undetermined Significance ; Multiple Myeloma ; Myeloid Cells ; Neoplasms, Plasma Cell ; Neutrophils* ; Ovarian Neoplasms ; Paraneoplastic Syndromes ; Sepsis

Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) that presents with abdominal pain, weight loss, and diarrhea. Although the etiology has not been fully elucidated, both environmental and genetic causes are known to be involved. In chronic inflammatory conditions such as IBD, B lymphocytes are chronically stimulated, and they induce monoclonal expansion of plasma cells, sometimes resulting in monoclonal gammopathy of undetermined significance. Immunomodulators that are commonly used to control inflammation, such as tumor necrosis factor-α (TNF-α) blockers could increase the possibility of hematologic malignancy. The pathogenesis of multiple myeloma in association with TNF-α inhibitor therapy is attributed to decreased apoptosis of plasma cell populations. Here, we describe a case of a 36-year-old male patient who was diagnosed with immunoglobulin A subtype smoldering multiple myeloma during the treatment for CD with infliximab and adalimumab. We report this case along with a review of the literature on cases of multiple myeloma that occurred in conjunction with CD.
Abdominal Pain ; Adalimumab ; Adult ; Apoptosis ; B-Lymphocytes ; Crohn Disease* ; Diarrhea ; Hematologic Neoplasms ; Humans ; Immunoglobulin A ; Immunologic Factors ; Inflammation ; Inflammatory Bowel Diseases ; Infliximab ; Male ; Monoclonal Gammopathy of Undetermined Significance ; Multiple Myeloma* ; Necrosis ; Plasma Cells ; Tumor Necrosis Factor-alpha ; Weight Loss

To detect the expression of miR-221/222 in serum and plasma cells in patients with monoclonal gammopathy of undetermined significance(MGUS) and multiple myeloma(MM), and to explore the possibility of miR-221/222 as biomarkers in the diagnosis and prognosis predicting of MGUS and MM.Bone marrow and serum samples from 14 patients with newly diagnosed MGUS, 81 patients with newly diagnosed or relapsed MM and 10 controls were collected from Sir Run Run Shaw Hospital of Zhejiang University and Tongde Hospital of Zhejiang Province during January 2013 and December 2015. The expressions of miR-221/222 in serum and in sorted CD138 positive plasma cells were detected by qRT-PCR, and the relative expression of miR-221/222 (Δct) was compared between the groups. Serum levels of miR-221 before and after treatment were compared in both remission group (=22) and refractory group (=13) in MM patients, and its correlation with serum level of β-MG was assessed using Pearson's correlation analysis.Serum levels of miR-221/222 in MGUS and MM groups were significantly higher than those in control group (all<0.01), while miR-221/222 levels in plasma cells were significantly lower in MGUS and MM groups than those in the control group (<0.05 or<0.01). No significant difference in miR-221/222 levels in serum and plasma cells was observed between MGUS group and MM group (all>0.05). There was no correlation between miR-221/222 levels in serum and plasma cells (=0.024 and -0.127, all>0.05), but miR-221 levels were correlated with miR-222 levels in both serum and plasma cells (=0.534 and 0.552, all<0.01). Receiver operating characteristic (ROC) curves showed that the areas under the curve (AUCs) of serum miR-221/222, plasma cell miR-221/222 in diagnosis of MGUS/MM were 0.968, 0.976, 0.801 and 0.727, respectively. There was no significant difference in serum level of miR-221 among MM patients with different paraprotein isotypes (>0.05), but serum level of miR-221 in patients with relapsed MM was higher than that in patients with newly diagnosed MM (<0.01). Compared with the patients with MGUS or MM stageⅠ and Ⅱ, patients with MM stage Ⅲ were of higher serum levels of miR-221 (<0.01). Serum level of miR-221 decreased after chemotherapy in the remission group (=51.5,<0.01), but such decrease was not observed in the refractory group (=67.5,>0.05). Serum level of β-MG was positively correlated with serum level of miR-221 (=0.524,<0.01).miR-221/222 in serum and plasma cells may be biomarkers for early diagnosis of MGUS, and are helpful for diagnosis and efficacy evaluation of MM.
Biomarkers ; analysis ; blood ; Bone Marrow ; chemistry ; Disease Progression ; Humans ; MicroRNAs ; analysis ; blood ; Monoclonal Gammopathy of Undetermined Significance ; genetics ; physiopathology ; Multiple Myeloma ; chemistry ; genetics ; physiopathology ; Myeloma Proteins ; analysis ; Paraproteinemias ; genetics ; physiopathology ; Prognosis ; Recurrence

OBJECTIVE: To investigate several abnormal genes by the fluorescence in situ hybridization (FISH) in multiple myeloma (MM), monoclonal gammopathy of undetermined significance (MGUS) and reactive plasmacytosis (RP), and to increase the diagnosis and differential diagnosis levels for these common plasma diseases. 
 METHODS: The clinical manifestations, image and laboratory tests and the FISH detection were retrospectively analyzed in 61 cases of newly diagnosed MM, 20 cases of MGUS and 20 cases of RP from August, 2012 to February, 2015 in the Xiangya Hospital of Central South University. 
 RESULTS: Fifty cases among 61 MM patients showed genetic abnormality by FISH technology. The total positive rate was 81.9%. Among them, 19 cases (31.1%) had 1q21 amplification, 18 cases (29.5%) lacked D13S319, 10 cases (16.4%) missed RB1, 10 cases (16.4%) had IGH translocation and 7 cases (11.4%) lacked p53 gene. The positive rate for two or more genes abnormal was 19.8% in 12 cases. However, in 20 cases of MGUS patients, the positive detection rate was 25%, including 4 cases (20%) of 1q21 augmentation and 2 cases (10%) of IGH translocation. There were not two or more abnormal genes in one case. While in RP cases, only 1 case of patients had D13S319 abnormal gene, and the positive rate was only 5%. There was significant difference (P<0.05) among the 3 groups. 
 CONCLUSION The positive detection rate is 81.9% in MM patients by FISH, which is significantly higher than that in patients with MGUS or RP. FISH technology can detect a variety of abnormal genes in MM. It is useful for the differential diagnosis and prognosis for MM, MGUS and RP.
Humans ; In Situ Hybridization, Fluorescence ; Monoclonal Gammopathy of Undetermined Significance ; Multiple Myeloma ; Paraproteinemias ; Retrospective Studies ; Translocation, Genetic