Pre Transplantation MGUS and Transformation to Multiple Myeloma in Kidney Transplantation: A Single Center Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4779-4779
Author(s):  
Harris V.K. Naina ◽  
Robert Kyle ◽  
Thomas M. Habermann ◽  
Samar Harris ◽  
Fernando G. Cosio ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Kidney Transplantation ◽  
Renal Transplantation ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
M Protein ◽  
Biclonal Gammopathy ◽  
Undetermined Significance

Abstract Background: Monoclonal gammopathy of undetermined significance (MGUS) is reported in 3 to 5 percent of population, with the prevalence increasing with advancing age. Patients with MGUS are at increased risk for progression to multiple myeloma or other plasma cell dyscrasias. There is a paucity of information on clinical outcomes of patients with MGUS undergoing renal transplantation. A retrospective study was performed to determine wether MGUS is a contraindication to renal transplantation. Methods: Data was collected from both the kidney transplant and MGUS database. The diagnosis of MGUS was made on the basis of either serum protein electrophoresis (SPEP) or immunofixation after excluding multiple myeloma, amyloidosis and monoclonal immunoglobulin deposition disease. Results: Between 1977 and 2004, 3518 patients underwent kidney transplantation of whom 23 patients had a preexisting monoclonal gammopathy of undetermined significance (MGUS). Fourteen (61%) of these patients were males. The median age at the time of transplant was 59 ±12 years. Ten patients (43.5%) had IgG Kappa (GK), 7 (30.4%) had IgG Lambda (GL), 2 (8.7%) had IgA Lambda (AL), 1 (4.3%) had IgA Kappa (AK), 2 (8.7%) had IgM Lambda (ML). One patient had a biclonal gammopathy GL and ML. Patients were monitored with either SPEP or immunofixation for median duration of 1542 days after transplantation. Thirteen patients had either no change or stable monoclonal protein, 6 had a decrease in their paraprotein level. Two patients had a mild increase in their paraprotein. Two patients with GK developed into biclonal gammopathy (GK and AK). The median follow up of this cohort after the renal transplant was 1783 days. Twelve (52%) patients remained alive at the time of the study. A patient with GK prior to the transplant who underwent kidney transplantation twice developed a biclonal gammopathy and was found to have increased plasma cells (20%) in bone marrow after 14 years. On follow up for 6 years, his M-protein remained stable. Another patient was found to have 17% plasma cells around the time of kidney transplantation. He had a stable M-protein at follow-up, but underwent a stem cell transplant for recurrent immunotactoid glomerulonephritis. Two (9%) patients developed more than 15% plasma cells in their bone marrow with a stable M-protein. None of the patients with a preexisting MGUS evolved into multiple myeloma. Conclusion: In this small study, the presence of MGUS prior to kidney transplantation did not appear to have increased the incidence of multiple myeloma post transplant. Therefore, MGUS by itself should not be considered as an absolute contraindication for renal transplantation.

scholarly journals The role of bone marrow microenvironment in the progression of multiple myeloma from monoclonal gammopathy of undetermined significance

2021 ◽  
Vol 16 (3) ◽  
pp. 26-32
Author(s):  
A. S. Khudovekova ◽  
Ya. A. Rudenko ◽  
A. E. Dorosevich
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Bone Marrow Microenvironment ◽  
Genetic Mutations ◽  
Microbiome Composition ◽  
The Impact ◽  
Undetermined Significance

Multiple myeloma is a tumor of plasma cells, one of the most common malignant blood diseases. It is preceded by a stage called monoclonal gammopathy of undetermined significance, from which true multiple myeloma develops in only a small percentage of cases. It was assumed that this process is associated with the accumulation of genetic mutations, but in recent years there is increasing evidence that the bone marrow microenvironment plays a key role in progression and that it can become a target for therapy that prevents the myeloma development. The review considers the role of mesenchymal stem cells, immune system cells, endotheliocytes, fibroblasts, adipocytes, osteoclasts and osteoblasts in multiple myeloma progression, as well as the impact of the sympathetic nervous system and microbiome composition.

The Natural History of Smoldering (Asymptomatic) Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3396-3396 ◽  
Author(s):  
Robert Kyle ◽  
Ellen Remstein ◽  
Terry Therneau ◽  
Angela Dispenzieri ◽  
Paul Kurtin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cell ◽  
Light Chain ◽  
Plasma Cells ◽  
M Protein ◽  
Cell Content ◽  
Bone Marrow Plasma ◽  
M Spike

Abstract Smoldering multiple myeloma (SMM) is characterized by a serum M protein ≥ 3g/dL and/or 10% or more of plasma cells in the bone marrow. However, the definition is not standardized, and it is not known whether both serum M protein levels and bone marrow plasma cell counts are necessary for diagnosis or if one parameter is sufficient. We reviewed the medical records and bone marrows of all patients from Mayo Clinic seen within 30 days of recognition of an IgG or IgA M protein ≥ 3g/dL or a bone marrow containing ≥ 10% plasma cells from 1970 to 1995. This allows for a minimum potential follow-up of 10 years. Patients with end-organ damage at baseline from plasma cell proliferation, including active multiple myeloma (MM) and primary amyloidosis (AL) and those who had received chemotherapy were excluded. A differential of the bone marrow aspirate coupled with the bone marrow biopsy morphology and immunohistochemistry using antibodies directed against CD138, MUM-1 and Cyclin D1 were evaluated in every case in order to estimate the plasma cell content. In all, 301 patients fulfilled either of the criteria for SMM. Their median age was 64 years and only 3% were less than 40 years of age; 60% were male. The median hemoglobin value was 12.9 g/dL; 7% were less than 10 g/dL, but the anemia was unrelated to plasma cell proliferation. IgG accounted for 75%, IgA 22%, and biclonal proteins were found in 3%. The serum light-chain was κ in 67% and λ in 33%. The median serum M spike was 2.9 g/dL; 11% were at least 4.0 g/dL. Uninvolved serum immunoglobulins were reduced in 81%; only 1 immunoglobulin was reduced in 31% and both were decreased in 50%. The urine contained a monoclonal κ protein in 36% and λ in 18% and 46% were negative. The median size of the urine M spike was 0.04 g/24h; only 5 (3%) were > 1 g/24h. The median bone marrow plasma cell content was 15 – 19%; 10% had less than 10% plasma cells, while 10% had at least 50% plasma cells in the bone marrow. Cyclin D-1 was expressed in 17%. Patients were categorized into 3 groups: Group 1, serum M protein ≥ 3g/dL and bone marrow containing ≥ 10% plasma cells (n= 113, 38%); Group 2, bone marrow plasma cells ≥ 10% but serum M protein < 3g/dL (n= 158, 52%); Group 3, serum M protein ≥ 3g/dL but bone marrow plasma cells < 10% (n= 30, 10%). During 2,204 cumulative years of follow-up 85% died (median follow-up of those still living 10.8 years), 155 (51%) developed MM, while 7 (2%) developed AL. The overall rate of progression at 10 years was 62%; median time to progression was 5.5 yrs. The median time to progression was 2.4, 9.2, and 19 years in groups 1, 2, and 3 respectively; correspondingly at 10 years, progression occurred in 76%, 59%, and 32% respectively. Significant risk factors for progression with univariate analysis were serum M spike ≥ 4g/dL (p < 0.001), presence of IgA (p = 0.003), presence of urine light chain (p = 0.006), presence of λ urinary light chain (p = 0.002), bone marrow plasma cells ≥ 20% (p < 0.001) and reduction of uninvolved immunoglobulins (p < 0.001). The hemoglobin value, gender, serum albumin, and expression of cyclin D-1 were not of prognostic importance. On multivariate analysis, the percentage of bone marrow plasma cells was the only significant factor predicting progression to MM or AL.

Prevalence of Post-Transplant Lymphoproliferative Disorder with Monoclonal Gammopathy of Unknown Significance in Patients Undergoing Kidney Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4778-4778
Author(s):  
Harris V.K. Naina ◽  
Robert Kyle ◽  
Thomas M. Habermann ◽  
Samar Harris ◽  
Fernando G. Cosio ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Kidney Transplantation ◽  
T Cell ◽  
Organ Transplantation ◽  
Monoclonal Gammopathy ◽  
Lymphoproliferative Disorder ◽  
M Protein ◽  
Monoclonal Protein ◽  
Post Transplant

Abstract Background: Post-transplant lymphoproliferative disorder (PTLD) represents one of the most serious consequences of immunosuppression in patients with solid organ transplantation. The incidence of PTLD is related to the organ transplanted and is dependent on the duration of follow-up. In various publications, the incidence of PTLD in renal transplantation ranges between 0.8% to 1.2%. In a previous study, the development of monoclonal (M) protein following liver transplantation is associated with the development of PTLD. In this study, we investigate this relationship in the kidney transplant population. Methods: A total of 3518 patients underwent kidney transplantation between 1963 to March 2006. These patients were cross referenced with the Monoclonal Gammopathy of Undetermined Significance (MGUS) database. Results: We identified 97 patients who had a monoclonal gammopathy either before or after transplantation. Patients with amyloidosis, multiple myeloma, heavy and light chain deposition disease and multi-organ transplantation were excluded from the analysis. A total of 69 patients met the inclusion criteria. Ten of the 69 (14.5%) patients developed PTLD. Median follow-up was 14.8 years. Twenty three patients had pretransplant MGUS, 20 patients developed MGUS following the transplant, and the other 26 did not have a monoclonal protein study prior to the transplant. Of the 23 patients who had a positive MGUS prior to the transplant, 4 patients (17.3%) developed PTLD, 1 patient developed EBV positive diffuse large cell lymphoma (DLCL), 1 developed EBV negative DLCL, 1 developed Hodgkin’s lymphoma and 1 developed increased plasma cells in bone marrow (20%) with stable M protein with no evidence of progression to multiple myeloma. None of these patients had a quantifiable M-protein prior to transplantation. The mean duration from diagnosis of MGUS to PTLD was 8.2 years (range 3 to 14 years). Of the 20 patients with a negative pre-transplant study for para proteniemia, 2 (10%) developed PTLD (T cell lymphoproliferative disorder). Two patients developed MGUS after the transplant at 1 and 12 years post transplant. It took an average of 15 years to develop PTLD after the diagnosis of MGUS. Four of the 26 patients who did not have a pretransplant study for MGUS developed PTLD. These included an EBV positive gamma delta type T cell lymphoproliferative disorder, an EBV positive plasmablastic lymphoma, one multiple myeloma and a plasmacytoma. The latter two patients had M-protein > 3g/dL. It took an average of 14 years after their transplant for these patients to develop PTLD. Conclusion: Our study showed that the development of a monoclonal protein in patients undergoing kidney transplantation is a strong risk factor for PTLD. Monoclonal protein study should be performed pretransplant and monitored post transplant as a surveillance of PTLD. Those who are positive or convert should be monitored closely for development of lymphoproliferative disorder.

scholarly journals Characterization of Monoclonal Gammopathy of Undetermined Significance Progression to Multiple Myeloma through Meta-Analysis of GEO Data

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4395-4395
Author(s):  
Jihad Aljabban ◽  
David Chen ◽  
Francesca Cottini ◽  
Saad Syed ◽  
Nabeal Aljabban ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Signaling Pathways ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Meta Analysis ◽  
Upstream Regulators ◽  
Undetermined Significance

Background: Monoclonal gammopathy of undetermined significance (MGUS) is characterized by plasma cell production of abnormal monoclonal protein, or M protein. While MGUS itself is asymptomatic, it generally carries a 1% per year risk to progression to multiple myeloma (MM). The etiology of MGUS, as well as why it progresses to MM in some cases, remains unclear. Moreover, it is not known why some MGUS patients, such as African Americans, have higher risk to progression to MM. Contrasting MGUS and MM can potentially highlight genes that differentiate benign gammopathies from malignant ones and may be involved in disease progression from MGUS to MM. Methods: We employed our STARGEO platform to tag samples from the NCBI Gene Expression Omnibus and performed two separate meta-analysis to compare MGUS and MM transcriptomes. For the first meta-analysis, we tagged MGUS plasma cells recovered from the bone marrow of 101 patients and tagged plasma cells from 64 healthy subjects as a control. For the second analysis. We tagged CD138+ cells from the bone marrow of 383 MM patients and used the MGUS tagged samples as a control. We then analyzed the signature in Ingenuity Pathway Analysis (IPA). Results: From our first meta-analysis of MGUS, we identified EIF2 signaling, regulation of EIF4 and p70S6K signaling, and JAK/STAT signaling as top canonical pathways. Top upstream regulators included TP53, TGFB1, and the proto-oncogene MYCN and MYC (with predicted activation). The most upregulated genes included pro-oncogenes such as KIT and MLLT3, which is well-studied in acute leukemia but not yet described in MGUS. Another top upregulated gene was NRG3, a myeloma growth factor. Additionally, our analysis highlighted key genes involved in transcription and epigenetic regulation. For example, there was upregulation of RBFOX2, which is involved in alternative splicing during oncogenesis and tumor progression, and of PARP15, a transcriptional repressor with poly(ADP-ribose) polymerase activity and candidate gene for drug targeting. Also, there was upregulation of the DNA damage-inducible gene GADD45A, found to promote global DNA methylation. Lastly, we found upregulation of COMMD3, a gene with a recently identified role in humoral activity and B cell migration. From our second meta-analysis comparing MM and MGUS directly, we identified mitochondrial dysfunction, oxidative phosphorylation, purine nucleotides de novo biosynthesis, and sirtuin signaling as top upstream regulators. Like our first analysis, TP53 (with predicted inhibition), TGFB1, and MYC (with predicted activation) were top upstream regulators. The most upregulated gene was NUP62, a nucleoporin and novel regulator of cell proliferation and inducer of MYC activity. Our analysis also illustrated pro-oncogenic signaling pathways such as the Wnt pathway through upregulation of the ubiquitin ligase RNF14 and serine/threonine kinase through upregulation of SRPK2. Moreover, we found upregulation of the super-enhancer DUSP4, a phosphatase whose over-activity may drive MM severity. Lastly, we found upregulation of lysosomal associated membrane protein LAMP5. LAMP5 was recently identified in single-cell RNA sequencing of MM patients and may play a significant role in disease. Conclusions: Our study illustrates signaling pathways in MGUS that are present in MM such as EIF2, JAK/STAT, and MYC signaling. We also illustrate gene activity in MGUS that may predispose to MM progression such as NRG3, RBFOX2, and PARP15. GADD45RA and COMMD3 may play novel roles in MGUS. Our second analysis highlighted disease activity that persist from MGUS to MM, such as MYC signaling. It is possible that the genes from this analysis that aims to distinguish MM from MGUS may be responsible for tipping the scales from benignity to malignancy. Genes such as DUSP4, RN14, LAMP5, and others could serve as novel biomarkers or targets to MM and risk of progression of MGUS to MM. Disclosures No relevant conflicts of interest to declare.

scholarly journals Relapse with BCR-ABL1 Elevation in Chronic Myeloid Leukemia after Progression to Multiple Myeloma from Monoclonal Gammopathy of Undetermined Significance with a Persistent KMT2D Mutation

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4608-4608
Author(s):  
Xiaofei Xu ◽  
Lan Zhang ◽  
Shengjie Wang ◽  
Keyi Jin ◽  
Chen DAN ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Gammopathy ◽  
Myeloid Leukemia ◽  
Plasma Cells ◽  
M Protein ◽  
Abnormal Growth ◽  
School Of Medicine ◽  
Medical Discipline ◽  
Immunofixation Electrophoresis ◽  
Undetermined Significance

Abstract Chronic myeloid leukemia (CML) and monoclonal gammopathy of undetermined significance (MGUS) are two different hematologic malignancies, the former arising from the myeloid cell lineage, and the latter arising from plasma cells. The concurrent diagnosis of CML and MGUS progression to multiple myeloma (MM) in one patient is an extremely rare event. A 59-year-old male was diagnosed with CML and MGUS with no discomfort in August 2012. Bone marrow (BM) aspiration suggested chronic myelogenous leukemia in chronic phase and perhaps myeloproliferative with 6.5% mature plasma cells (Figure 1A). FISH analysis detected that the BCR-ABL1 expression was 130%. And Next-generation sequencing (NGS) of BM showed: ASXL1 , KMT2D , SPEN , BRINP3 , ANKRD26 , PLCG1 , CUX1 were mutated (Figure 2I). The patient started oral imatinib 400 mg per day and achieved a complete cytogenetic response at 3 months. In September 2019, his IgG levels were 2,790 mg/dl (Figure 2J and serum immunofixation electrophoresis revealed monoclonal (M) protein of IgG-Lambda type (Figure 1E). BM aspiration revealed 9.5% plasma cell infiltration, including 6% mature plasma cells and 3.5% proplasmacyte (Figure 1C and 2H). Flow cytometry in BM showed 6.3% plasmacytoma and abnormal cell expressing CD38+CD138+CD56+CD117+clambda+ (Figure 1F). BM biopsy showed hematopoietic hyperplasia with abnormal growth of immature cells (Figure 1B). Fluorescent in situ hybridization (FISH) was negative. Mutations of KMT2D, SPEN, BRINP3, ANKRD26, PLCG1, CUX1, and ZMYM3 still existed(Figure 2I). In January 2020, examination of a new BM aspiration revealed that mature plasma cells were 3% and plasmablast and proplasmacyte were 4.5% (Figure 2H). In February 2020, he stopped IM therapy with undetectable BCR-ABL1 copies because he met the requirement of stopping TKI therapy . In March 2020, IgG levels were 3520 mg/dl and serum immunofixation electrophoresis still revealed monoclonal (M) protein of IgG-Lambda type. His BM aspiration demonstrated 13.5% plasma cells in April 2020 (Figure 2B and 2H). Flow cytometry in BM showed 6.44% (Figure 2F). BM biopsy showed extremely increased proliferation with abnormal growth of abnormal cells (Figure 2A). FISH demonstrated the presence of t(4;14)(p16;q32)(IGH/FGFR3) , 13q14 deletion（RB-1） and 13q14.3 （D13S319） (Figure 2C, 2D and 2E). The patient was diagnosed as MM (IgGλ type, D-S stage IA; ISS stage II) . BCR-ABL1 copies were still not detected at this point (Figure 2G). The patient continued his follow-up treatment of MM without chemotherapy.However, in June 2020, he was considered to have a molecular relapse with 0.2013% BCR-ABL1 copies in the peripheral blood (Figure 2G). NGS showed that the variant allele fractions of KMT2D, SPEN, BRINP3, ANKRD26, PLCG1, CUX1, and ZMYM3 mutations were similar to former . He restarted 400 mg daily IM therapy and BCR-ABL1 copies were undetectable againafter one month therapy (Figure 2G). BM aspiration revealed that the percentage of plasma cells increased to 25.5% in August 2020 (Figure 2H). Then the patient was started on treatment for ISS stage II standard risk myeloma with ID regimen: ixazomib 4 mg on days 1, 8 , 15 and dexamethasone 20 mg on days 1, 8, 15 , 22 in 28-day cycles. After 6 cycles , the patient got VGPR. BM aspiration demonstrated 13% plasma cells (Figure 2H). And he continued to receive myeloma treatment and imatinib . BCR-ABL1 were <MR4.5 (Figure 2G). Our research indicated that KMT2D mutation may make MGUS progress to MM with NK cells functional defects and then promote the recurrence of BCR-ABL1. Co-existence of these two diseases is rare, therefore, additional investigations are warranted. Acknowledgment:The research was supported by the Public Technology Application Research Program of Zhejiang, China (LGF21H080003), the Key Project of Jinhua Science and Technology Plan, China (2020XG-29 and 2020-3-011), the Academician Workstation of the Fourth Affiliated Hospital of the Zhejiang University School of Medicine (2019-2024), the Key Medical Discipline of Yiwu, China (Hematology, 2018-2020) and the Key Medical Discipline of Jinhua, China (Hematology, 2019-2021). Correspondence to: Dr Jian Huang, Department of Hematology, The Fourth Affiliated Hospital of Zhejiang University School of Medicine. N1 Shangcheng Road. Yiwu, Zhejiang, Peoples R China. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Five years’ Follow-Up Study For Frequency Of Monoclonal Gammopathy Of Undetermined Significance (MGUS) In a Korean Elderly Urban Cohort

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5332-5332
Author(s):  
Yun-Gyoo Lee ◽  
Soo-Mee Bang ◽  
Jeong-Ok Lee ◽  
Song Jung Han ◽  
Kim Ki Woong ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Gammopathy ◽  
M Protein ◽  
Risk Of Death ◽  
Follow Up Study ◽  
Significant Difference ◽  
Korean Elderly ◽  
Second Wave ◽  
Undetermined Significance

Abstract Background The prevalence of monoclonal gammopathy of undetermined significance (MGUS) increases with patient age and varies by race. However, reliable data on the epidemiology of MGUS is limited in Korea. We previously reported the prevalence of MGUS among 1000 participants of a Korean Elderly Urban Cohort recruited from 2005 to 2006 (First Wave, Park HK Am J Hematol. 2011;86:752-5); age and gender-adjusted prevalence of MGUS was estimated as 3.3% (95% confidence interval [CI] = 2.0-4.6%). Here, we report the five years’ follow-up study for frequency of MGUS between 2010 and 2011. Methods Korean Longitudinal Study on Health and Aging (KLoSHA) is a population-based, prospective cohort study of health, aging, and common geriatric diseases in a population aged ≥ 65 years in Seongnam-si, a satellite city of Seoul. Of the random sample of 1118 candidates from 61,730 Korean elderly individuals, 698 respondents agreed to participate in baseline KLoSHA study between 2005 and 2006. A total of 680 with available samples were screened for MGUS. We followed them and collected their serum between 2010 and 2011 (Second Wave). The screening of MGUS in the Second Wave was performed using serum protein electrophoresis followed by immunofixation assays; MGUS was defined by the presence of a serum monoclonal protein (M-protein), at a concentration <3 g/dL, and in the absence of end organ damage. Bone marrow study was not performed unless the patient was suspicious of multiple myeloma. To validate complete follow-up data, information regarding vital status was obtained from the National Population Registry of Korea National Statistical Office by using a unique resident registration number. Overall survival was calculated from the date of First wave to death from any cause. Results Of the 680 respondents (21 with MGUS, 659 without MGUS) in the First Wave, 361 (53%) agreed to participate in the Second Wave. Causes of nonattendance were death in 20%, refusal in 19%, move to other area in 6%, and loss to contact in 3%. Of the 361 respondents, 10 were identified to have MGUS. Overall frequency of MGUS is 2.8% (95% CI: 1.3 - 5.0%). Among 21 patients with MGUS in the First Wave, 9 were followed up in the Second Wave. Six of them showed persistent MGUS. One of them showed mild anemia with persistent M-protein of 1.4g/dL suggestive of progression to multiple myeloma, but was not confirmed because of early death just after screening. Interestingly, M-protein was disappeared in remaining 2 patients with MGUS in the First wave. Among 659 respondents without MGUS in the First Wave, 352 were followed up in the Second Wave. Four of them were newly diagnosed with MGUS. In Kaplan-Meier survival analysis, there was no significant difference of survival between respondents with MGUS and without MGUS in the First Wave (P = 0.66 by Log-rank test). Conclusion Five years’ follow-up data showed the natural clinical course of MGUS. The diagnosis of MGUS was not associated with an increased risk of death in Korean elderly population. The interesting finding was that M-protein was disappeared in some patients with MGUS. High rate of non-attendance (47%) in Second Wave is the major limitation. Disclosures: No relevant conflicts of interest to declare.

Monoclonal Gammopathy of Undertermined Significance (MGUS): Clinical Predictors of Malignant Transformation in 434 Patients with a Long Follow-Up from a Single Institution.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4838-4838
Author(s):  
L. Rosiñol ◽  
S. Montoto ◽  
J. Bladé ◽  
M.T. Cibeira ◽  
M. Rozman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Malignant Transformation ◽  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
M Protein ◽  
Single Institution ◽  
Protein Size ◽  
Bone Marrow Plasma

Abstract Background: MGUS is a common disorder characterized by the presence of a small serum M-protein in individuals with no evidence of multiple myeloma (MM), Waldenström’s macroglobulinemia (WM) or primary amyloidosis (AL). Although about one fourth of these individuals will evolve into a malignant disease with a transformation rate of 1% per year, there are not well-established predictors of outcome. Aim: To identify predictor features of malignant transformation in a large series of patients with MGUS and prolonged follow-up. Patients and methods: Four hundred and thirty-four patients (200 M/234 F; median age 66 years) diagnosed with MGUS in a single institution from September 1970 to January 2001 with a minimum follow-up of one year were included in the study. All patients had an M-protein size < 30g/L. Bone marrow aspirates were reviewed independently by two of the authors and the proportion of bone marrow plasma cells (BMPC) were estimated from a 500 cell-count by each observer. The median follow-up was 5.2 years (range: 1–28.8 years) with 84 patients followed for more than 10 years. Results: The type of M-protein was IgG in 67.2% of the cases, IgA in 18.8%, IgM in 11.9%, light chain in 1% and biclonal in 1%. The light chain was kappa type in 56.4% of the patients. The median M-protein size was 15.6 g/L (<10 g/L in 10.8%, 10–20 g/L in 61.7%, and > 20g/L in 27.4%). The median percentage of BMPC in 305 reviewed samples was 4.6% (range: 0.4–25). After a median follow-up of 5.2 years, 50 patients (11.5%) have evolved into a malignant monoclonal gammopathy (44 MM, 5 WM and 1 AL). The median time to progression was 5.4 yrs (range: 1.4 – 16.9). The risk of transformation was 15.4% (95% CI: 10.5–20.3) and 34% (95% CI 22.6–45.3) and 34% (95% CI: 22.6–45.3) at 10 and 20 years, respectively. The variables associated with a higher risk of transformation were IgA-type (p=0.003), kappa light chain (p=0.009), the amount of M-protein (<15 vs >15 g/L, p=0.005) and the percentage of BMPC (<5% vs >5%, p=0.007). Conclusions: In this series of patients with MGUS, the type (i.e. IgA or kappa) and size of M-protein (>15g/L) as well as the percentage of bone marrow plasma cells (>5%) significantly predicted malignance transformation.

Multiple Myeloma in Association With Sarcoidosis

2002 ◽  
Vol 126 (3) ◽  
pp. 365-368
Author(s):  
Filiz Şen ◽  
Karen P. Mann ◽  
L. Jeffrey Medeiros
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Bone Marrow Aspiration ◽  
Bone Marrow Examination ◽  
Medical Attention ◽  
Non Hodgkin Lymphoma ◽  
Noncaseating Granulomas ◽  
Undetermined Significance

Abstract The association of sarcoidosis with Hodgkin disease and non-Hodgkin lymphoma is well known. However, multiple myeloma also can occur rarely in association with sarcoidosis. We describe a patient with sarcoidosis who subsequently developed multiple myeloma. The patient was a 49-year-old woman with a 4-year history of severe, chronic, active sarcoidosis involving her lungs, lymph nodes, eyes, and bone marrow. During the initial clinical workup, a serum monoclonal paraprotein was detected and bone marrow examination revealed a slight increase in plasma cells (4%), in addition to noncaseating granulomas. Thus, the diagnoses of monoclonal gammopathy of undetermined significance and sarcoidosis were established simultaneously. She sought medical attention for her current illness when she developed low back pain and weakness of her lower extremities. Serum protein electrophoresis and immunofixation revealed a monoclonal paraprotein, immunoglobulin (Ig) G κ type, and quantification revealed an IgG level of 46.67 g/L (normal, 5.88–15.73 g/L). Bone marrow aspiration and biopsy revealed multiple myeloma and sarcoidosis. Including this patient, 11 cases of sarcoidosis and multiple myeloma have been reported to date, including 3 patients with monoclonal gammopathy of undetermined significance preceding the onset of multiple myeloma. In this case, as in most of the cases reported previously, sarcoidosis preceded the development of multiple myeloma.

scholarly journals Progression of Monoclonal Gammopathy with Undetermined Significance to Multiple Myeloma Diagnosed by Kidney Biopsy: A Case Report

2015 ◽  
Vol 5 (3) ◽  
pp. 180-186 ◽  
Author(s):  
Jin Hae Kim ◽  
Ji Won Kim ◽  
Young Nam Kim ◽  
Hye In Kim ◽  
Jun Young Kim ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Renal Function ◽  
Case Report ◽  
Monoclonal Gammopathy ◽  
Kidney Biopsy ◽  
M Protein ◽  
Tubular Proteinuria ◽  
Risk Of Progression ◽  
Undetermined Significance

Monoclonal gammopathy with undetermined significance (MGUS) carries a risk of progression to multiple myeloma, and progression is usually diagnosed with changes in M-protein or bone marrow biopsy. We report a case of 62-year-old female patient showing MGUS progression to multiple myeloma without significant changes in M-protein but diagnosed by kidney biopsy. During the follow-ups, azotemia and tubular proteinuria were aggravated without elevation of M-protein. Kidney biopsy showed intratubular and glomerular inclusions associated with plasma cell dysplasia. The progression of MGUS to multiple myeloma was diagnosed by this kidney biopsy. The patient's renal function and tubular proteinuria were markedly improved after chemotherapy.

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