scholarly journals Significance of Bone Marrow Plasma Cell Percentage in Patients with Monoclonal Gammopathy of Unknown Significance Developing Multiple Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5688-5688
Author(s):  
Mona L Vekaria ◽  
Bharat Rao ◽  
Philip Kuriakose

Abstract Introduction: Monoclonal gammopathies are characterized by the detection of a monoclonal immunoglobulin in the serum or urine and underlying proliferation of a plasma cell/B lymphoid clone. (1) Patients with monoclonal gammopathy of undetermined significance (MGUS) have a clonal plasma cell population in the marrow (<10%) and secrete a monoclonal protein in the serum (<3g/dL) and/or urine. However, they lack clinical features of overt Multiple Myeloma (MM) (lytic bone lesions, anemia, renal impairment and hypercalcemia). In a study from the Mayo Clinic, 59 of 241 patients with MGUS (24%) developed MM over a period of 22 years. (2) The interval from recognition of monoclonal protein to diagnosis of MM ranged from 2-29 years, indicating that patients with MGUS need to be followed indefinitely. Many risk factors have been looked at to identify those with MGUS who are at the highest risk to progress into MM. We hypothesize that a higher number of plasma cells would correlate with a greater risk of progression to MM and sought to find out if this could be documented by arbitrarily dividing patients between < or ≥5% plasma cells seen on initial bone marrow biopsy. Methods: We retrospectively reviewed patients diagnosed with MGUS at Henry Ford Hospital between 1999-2013 who underwent a bone marrow biopsy for documenting plasma cell percentage. In addition to this, we also recorded serum hemoglobin, calcium, creatinine, monoclonal protein type and amount, serum free light chains, beta-2 microglobulin and urine for monoclonal protein at the time of diagnosis of MGUS as well as last completed values. For patients that had skeletal surveys we noted if lytic lesions were present at diagnosis, as well as cytogenetics and karyotype evaluations on bone marrow biopsy samples, if completed. Results: 120 patients with bone marrow biopsies were reviewed. Out of this 17 patients were noted from initial bone marrow biopsy to have ≥10% plasma cells. The remaining 103 patients were categorized as having MGUS. While we were not able to complete full statistical analyses, we did note that 14 of these 103 (13.6%) patients went on to develop overt MM. Further evaluation of these patients revealed that 8 of 14 (57%) had bone marrow biopsies showing ≥5% plasma cells. Interestingly the average time to progression into MM in this subgroup was 1,879 days whereas in the 6 of 14 (43%) with bone marrow biopsy showing <5% plasma cells had average time to progression into MM of 1,965 days. Abnormal cytogenetics and karyotypes of the bone marrow biopsy were also seen in 37.5% of the subgroup of patients with ≥5% plasma cells whereas it was only seen in 16.7% of the subgroup of patients with <5% plasma cells. With statistical data analyses we hope to prove significance in the above collected data as well as make further correlations in regards to risk factors in patients with MGUS. Conclusion: While we have not been able to complete full statistical analyses of the collected data yet, basic review of the above patients with MGUS and ≥5% plasma cells in the bone marrow biopsy showed a trend to develop MM faster by an average of 86 days than those that had <5% plasma cells. These same patients also were more likely to have abnormal cytogenetics and karyotypes of their bone marrow biopsies. There is a need for further investigations to be done in patients with MGUS and higher risk features. It is important that hematologists be able to recognize a high risk MGUS patient as this would lead to closer monitoring and consideration for earlier aggressive treatment to potentially delay progression into overt MM. Disclosures No relevant conflicts of interest to declare.

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8117-8117
Author(s):  
J. Singh ◽  
A. K. Malani ◽  
C. H. Huang ◽  
M. Hashmi ◽  
S. C. Mathur ◽  
...  

8117 Monoclonal gammopathy of undetermined significance (MGUS) increase in prevalence with age and it is associated with risk of progression to plasma cell disorder. According to ASH guidelines, patients (pts) should have a complete blood count (CBC), creatinine, calcium, and a complete bone survey and periodic follow up. There has been no clear-cut guideline regarding the role of bone marrow biopsy in these patients. There is suggestion in the literature that bone marrow aspiration and biopsy is indicated if the M protein is 1.5 g/dL. Hypothesis We hypothesize that the increase in serum immunoglobulin is correlated with an increase in plasma cell in the bone marrow biopsy. Methods: We performed a retrospective chart review of 327 MGUS veteran patients seen from 2002 to 2005. Diagnostic criteria for MGUS were defined as <3 g/dL serum monoclonal protein, <10 % plasma cells in the bone marrow and absence of radiographic or laboratory abnormality related to the plasma cell proliferative process. Patients with smoldering myeloma were excluded. Bone marrow biopsies were available on 97/327 patients. Bone marrow biopsy with plasma cell percentage, serum protein electrophoresis (SPEP) and immunofixation (SFE), and immunoglobulin levels of these patients were retrieved and statistical analysis was performed by using Pearson correlation coefficient and linear regression analysis to detect the correlation between plasma cell percentage and immunoglobulin levels. Results: Of the 97 patients whom the bone marrow biopsy was available, 66 patients had IgG, 15 had IgA and 16 had IgM monoclonal paraprotein. There was linear correlation between serum IgG and IgA levels with the percentage of plasma cells in the bone marrow. (p< 0.001 and < 0.02 respectively. By regression analysis, using a cut off value of 10% plasma cells in the bone marrow, the predicted level of IgG and IgA immunoglobulin was 2124 mg /dl and 1564 mg/dl respectively. There was no correlation between IgM immunoglobulin and plasma cell percentage in the marrow. Conclusion: There is a linear correlation between serum IgG and IgA immunoglobulin with plasma cell percentage in the bone marrow. Bone marrow biopsy with plasma cell percentage of 10% or higher may be predicted in patients with MGUS with IgG or IGA above 2g/dl and 1.5g/dl respectively. No significant financial relationships to disclose.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5067-5067
Author(s):  
Meletios Athanasios Dimopoulos ◽  
Evangelos Terpos ◽  
Maria Gkotzamanidou ◽  
Evangelos Eleutherakis-Papaiakovou ◽  
Magdalini Migkou ◽  
...  

Abstract Abstract 5067 The incidental finding of a monoclonal gammopathy during workup for various conditions or in the context of a routine check-up is increasingly common. Several “patients” are then referred for diagnostic evaluation of their monoclonal gammopathy and additional workup is needed. It has been proposed that a bone marrow (BM) aspirate and biopsy is indicated when the monoclonal protein (M-protein) is ≥1.5 g/dL, when abnormalities are noted in the complete blood cell count, serum creatinine level, serum calcium level, or radiographic bone survey, in individuals with non-IgG monoclonal gammopathy and in those with an abnormal serum free light chain (FLC) ratio. The aim of this study was to identify factors that could aid in the evaluation of individuals presenting with asymptomatic monoclonal gammopathy and in whom invasive diagnostic testing with a bone marrow biopsy is considered. Thus, we analyzed our database and identified patients who were referred to the Department of Clinical Therapeutics of the University of Athens, Greece, for evaluation of asymptomatic monoclonal gammopathy and in whom a BM trephine biopsy, a serum and urine protein electrophoresis (SPEP) with immunofixation and quantitative immunoglobulins were performed. SPEPs were scanned and M-protein was measured using imaging analysis software. Patients with a monoclonal M-protein ≥ 3 g/dl (30 g/L), i.e. those diagnosed with asymptomatic/smoldering myeloma (SMM) or Waldenstrom's macorglobulinemia based on the standard criteria, were not included in the analysis. Clonality of BM plasma cells or lymphoplasmacytes was assessed by immunohistochemistry. Patients who eventually were diagnosed with plasma cell related conditions (i.e. amyloidosis, peripheral neuropathy, dermatoses, etc.) were also excluded from the analysis. Our analysis included 161 patients: 53% were females, median age was 64 year (range 33–89 years), 53% had a monoclonal IgG protein, 15.5% had a monoclonal IgA protein, 24% a monoclonal IgM protein and 2.5% had only a monoclonal light chain, while 4% had a biclonal protein. In 64% of patients the monoclonal light chain was kappa and in 37% was lambda. The median serum M-protein was 0.948 g/dl (range 0.1–2.99 g/dl); 52% of patients had an M-protein of <1 g/dl and 79% of <2 g/dl. Immunoparesis of at least one of the uninvolved immunoglobulins was present in 38% of cases and of both of the uninvolved immunoglobulins in 6%. Median BM infiltration by monoclonal plasma cells or lymphoplasmacytes was 15%. In 66.5% of individuals there was a BM infiltration of ≥10% by monoclonal plasma cells or lymphoplasmacytes, while in 10% of the studied cases the BM infiltration was ≥50%. A significant correlation of the size of M-protein and of the infiltration of the BM was found (R=0.592, p<0.001). However, 27% of patients with M-protein <0.5 g/dl had ≥10% clonal plasma cells or lymphoplasmacytes in their BM biopsies. The respective rates were 46% for those with M-protein <1 g/dl, 54% for those with M-protein 1.5 g/dl and 58% for those with M-protein <2 g/dl. Ninety per cent of those who had immunoparesis of at least one of the uninvolved immunoglobulins had ≥10% clonal plasma cells or lymphoplasmacytes. A BM infiltration of ≥10% was more frequent in individuals with a monoclonal IgG or IgA protein (72% and 80%, respectively) vs. 45% of those with a monoclonal IgM protein (p=0.015). Light chain isotype, age and gender were not predictive of the degree of BM plasma cell infiltration. In multivariate analysis, immunoparesis of at least one of the uninvolved immunoglobulins (OR: 6.45, 95% CI: 2.32–18, p<0.001), an IgG or IgA monoclonal protein (OR: 2.67, 95% CI: 1.1–6.4, p=0.028) and an M-protein of ≥1 g/dl (OR: 5.4, 95% CI: 2.23–13) were independently associated with the presence of ≥10% of clonal infiltration in BM biopsy. By combining the above risk factors we found that in those who had all three, 97% had ≥10% clonal cells in the BM biopsy, while in those with 0–1 of the above factors the probability to find ≥10% clonal cells was 43%. These findings indicate that even patients with low risk for BM infiltration by clonal plasma cells, may be diagnosed as SMM when a BM biopsy is performed. In conclusion, our data on a large number of individuals with asymptomatic monoclonal gammopathy who underwent a BM biopsy may indicate that the latter exam may provide useful information and could be included in the standard initial workup of these individuals. Disclosures: No relevant conflicts of interest to declare.


2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S110-S110
Author(s):  
A Vijayanarayanan ◽  
K Inamdar ◽  
M Menon ◽  
P Kuriakose

Abstract Introduction/Objective Myeloma diagnosis by a pathologist requires 10% plasma cells (PC) or a biopsy proven plasmacytoma in addition to myeloma defining events. PC% &gt; 60% is a biomarker of malignancy under this definition. WHO allows for assesment of plasma cell percentage either by aspirate count or by CD138 immunohistochemistry (IHC). There is lack of consensus on aspirate smear adequacy for PC% estimation. Uneven distribution of plasma cells, hemodilution and/or patchy infiltration can lead to gross underestimation. We compared PC% by aspirate count and CD138 IHC and established corelation with serum protein electrophoresis (SPEP) values. Methods 67 myeloma cases were included after excluding cases with suboptimal or inadequate aspirate smears. Two hematopathologists evaluated the diagnostic marrow (therapy naive) for PC% by aspirate count and CD138 IHC on biopsy/clot section. Corresponding SPEP and Free light chain (FLC) values were obtained. Correlation coefficent was calculated using Pearson correlation coefficient (GraphPad Prism). Results The Ig subtypes included IgG (41/67) and IgA (17/67). 12 cases had available FLC values. Both average and median PC% by CD138 IHC was considerably higher (50%, 52%) compared to aspirate count (29%, 21%). However, PC% by aspirate smear count and CD138 IHC demonstrated a significant linear correlation (r=0.71, p60% by CD138 (and not by aspirate count). Conclusion CD138 IHC based PC% is consistently higher, nevertheless, statistically significant linear corelation is observed between aspirate count PC% and CD138 IHC. A significant linear correlation is observed between CD138 IHC and SPEP (IgG and IgA), however, no such correlation is observed with aspirate count. More cases were diagnosed as myeloma (11%) and higher propotion of cases (35%) had biomarker of malignancy i.e. PC% &gt;60% by CD138 IHC. Based on these findings, we propose estimation of PC% by CD138 immunostain be a recommended standard practice for better clinicopathologic and biologic correlation.


2003 ◽  
Vol 25 (4) ◽  
pp. 167-171 ◽  
Author(s):  
G. M. Markey ◽  
P. Kettle ◽  
T. C. M. Morris ◽  
N. Connolly ◽  
H. Foster

Direct measurement of monoclonal plasma cell mass in bone marrow biopsies may be a useful parameter to establish in plasma cell dyscrasia. In this study monoclonal plasma cells/mm2in light chain immunoglobulin immunostained archival bone marrow sections from 22 patients in whom a diagnosis of multiple myeloma (MM) had been excluded but who had monoclonal proteins were counted by two observers at light microscopic level. There was good correlation between the counts of the two observers. The levels of monoclonal plasma cells/mm2in biopsies were not related to the % counts in the aspirates taken at the same time as the biopsies. Three of seven patients with biopsy levels in excess of the polyclonal levels in patients without plasma cell dyscrasia developed progressive MM within the observation time. Monoclonal plasma cell levels/mm2of bone marrow biopsies can be measured and they provide a useful parameter for the assessment of patients with low volume plasma cell dyscrasia. Colour figure can be viewed onhttp://www.esacp.org/acp/2003/25‐4/markey.htm.


2019 ◽  
Vol 19 (10) ◽  
pp. e333
Author(s):  
M Hasib Sidiqi ◽  
Mohammed Aljama ◽  
Shaji Kumar ◽  
Dragan Jevremovic ◽  
Francis Buadi ◽  
...  

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4044-4044
Author(s):  
Wesley Witteles ◽  
Ronald Witteles ◽  
Michaela Liedtke ◽  
Sally Arai ◽  
Richard Lafayette ◽  
...  

Abstract Abstract 4044 Background: Conventionally, multiple myeloma is believed to coexist in approximately 10% of AL amyloidosis patients. However, it is unclear whether this figure is too low based on current World Health Organization criteria. These criteria, mainly created to differentiate myeloma from monoclonal gammopathy of undetermined significance, include the presence of ≥ 10% plasma cells on a bone marrow biopsy or aspirate as being diagnostic of myeloma. Aims: To define the frequency and relevance of a concomitant diagnosis of myeloma in patients with AL amyloidosis. Methods: Records from consecutive patients with biopsy-proven AL amyloidosis treated at the Stanford University Amyloid Center were reviewed. Plasma cell percentages were determined by manual counts from bone marrow aspirate smears and by CD138 immunohistochemistry (IHC) performed on bone marrow core biopsies. Results: A total of 41 patients (median age 61 years, 32% female) were evaluated. The median number of organs involved with amyloidosis was 2 (range 1–4), with 28 patients (68%) having cardiac involvement, 22 patients (54%) having renal involvement, 15 patients (37%) having gastrointestinal involvement, 12 patients (29%) having soft tissue involvement, and 10 patients (24%) having nervous system involvement. All patients had bone marrow biopsies and aspirates performed at the time of amyloid diagnosis, with most undergoing both manual counts of plasma cells from aspirates and IHC from core biopsies. Based on conventional criteria, manual aspirate counts defined 15/28 (54%) patients as having myeloma, and IHC defined 26/31 (84%) patients as having myeloma (p=0.01). Only nine patients had a detectable serum paraprotein on immunofixation (median 1.1 g/dl, range 0.4–2.6). 81% of patients had an elevated serum free light chain (85% lambda), with a median level of 37.3 mg/dl (range 8.6–256 mg/dl). Compared to the frequency of elevated plasma cells, the prevalence of anemia (29%), hypercalcemia (14%), impaired kidney function (21%), and lytic lesions (7%) was low. After a median follow-up of 13 months (range 1–127 months), the one-year overall survival (74% vs. 58%) and three-year overall survival (50% vs. 50%) was not significantly different between patients with ≥10% plasma cells and patients with <10% plasma cells (p=NS). Discussion: As defined by bone marrow plasma cell involvement, a strikingly high percentage (84%) of AL amyloidosis patients would be considered to have concurrent myeloma. This figure is much higher than has been traditionally quoted in the literature, likely due to the utilization of newer methods of counting plasma cells. There was a low prevalence of myeloma-associated end-organ effects (hypercalcemia, anemia, renal insufficiency, lytic bone lesions), and a myeloma diagnosis had no impact on survival. Conclusion: In this cohort of AL amyloid patients, concomitant myeloma was present in the vast majority of patients using modern diagnostic techniques. The significance of this diagnosis appears to be minimal – calling into question whether the diagnostic criteria for myeloma should be redefined in this population. Disclosures: Witteles: Celgene: Research Funding. Liedtke:Celgene: Lecture fee, Research Funding. Schrier:Celgene: Research Funding.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5008-5008
Author(s):  
Maria Kraj ◽  
Barbara Kruk ◽  
Krzysztof Warzocha ◽  
Andrzej Szczepinski ◽  
Kelly Endean ◽  
...  

Abstract Abstract 5008 A 48 year old man was referred to the Institute of Hematology and Transfusion Medicine, Warsaw, Poland in April 2008 with anemia (Hemoglobin; 10. 4 g/dl) and mild renal impairment (eGFR; 75. 4 mL/min/1. 73m2). An initial diagnostic monoclonal protein screen (serum protein electrophoresis (SPE), serum immunofixation electrophoresis (IFE) and serum free light chain (FLC) analysis) revealed an IgAλ monoclonal protein (0. 8g/dL) with monoclonal serum FLC and an abnormal serum FLC κ/λ ratio (0. 0001; RI, 0. 26–1. 65). A bone marrow biopsy at that time confirmed 60% involvement of monoclonal λ - restricted plasma cells; a bone survey did not detect any osteolysis. The patient was diagnosed with multiple myeloma (MM) (ISS stage I, Durie and Salmon stage IA) and was initially treated with 6 cycles of vincristin, doxorubicin and dexamethasone (VAD). The patient responded well to the induction treatment and subsequently underwent a successful autologous stem cell transplantation (ASCT). The patient was monitored for 3 years subsequent to the ASCT with both serum and urine electrophoresis, serum FLC analysis (Freelite) and heavy chain/light chain (HLC) immunoassays (Hevylite). Sixteen months following the ASCT the dFLC (involved λ FLC– uninvolved κ FLC) concentration began to increase, the FLC κ/λ ratio became abnormal with a trace of λ Bence Jones protein (BJP) detected by urine IFE. However, both SPE and IFE were normal and the HLC ratio (IgAλ/IgAκ) was within the normal range. During the next 9 months the dFLC continued to increase and a λ BJP could now be clearly detected on the urine IFE. 27 months following the ASCT the patient sustained a pathological fracture of the tibiae and was referred to our centre 4 months later. At this point, the dFLC concentration was highly elevated (3168 mg/L) with a λ BJP detectable by both serum and urine IFE. However, there was no detectable monoclonal intact immunoglobulin by serum IFE or HLC analysis, indicating disease relapse by a separate FLC clone; referred to as light chain escape (LCE). A bone marrow biopsy revealed 15% involvement of λ restricted plasma cells; this time a bone survey identified osteolysis. The patient was diagnosed with progression of multiple myeloma and received 6 cycles of bortezomib, cyclophosphamide and dexamethasone (VCD regimen). He responded well to treatment and 3 years following the ASCT achieved a CR as indicated by a normalized κ/λ FLC ratio, negative immunofixation with 1–3% bone marrow plasma cells. The patient is now well and able to continue with normal life. In this case study the increase in the dFLC levels was the first indication of disease progression and highlights the importance of monitoring intact immunoglobulin MM patients with serum FLC immunoassays for early detection of LCE. Disclosures: Endean: The Binding Site Group Ltd: Employment. Harding:Binding Site: Employment.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5338-5338
Author(s):  
Finella MC Brito-Babapulle ◽  
Tanya Cranfield ◽  
Robert B Corser ◽  
Helen Dignum ◽  
Christopher James ◽  
...  

Abstract Mouse eosinophils have been shown in 2011 to be required for the maintenance of long lasting plasma cells in the bone marrow and in maintaining the bone marrow plasma cell microenvironment. Human eosinophils have been shown by Wong et al to support multiple myeloma cell proliferation via a mechanism independent of IL6. We looked at bone marrow biopsies taken from patients who had a paraprotein and in whom a diagnosis of multiple myeloma was suspected. These samples were taken solely for the purposes of diagnosisng multiple myeloma and were retrospectively reviewed from the point of view of degree of eosinophil infiltration and its correlation with tumour load, bone lytic lesions, plasma cell morphology, whether blastic, crystalline inclusions, Mott cells, flame cells and or lymphoplasmacytoid. There were no cases of IGD or E myeloma or osteosclerotic myeloma.Nonsecretory myeloma and cases of light chain myeloma with or without amyloid were included in the series. Biopsies were not performed from osteolytic lesion unless biopsy was necessary to make a diagnosis of myeloma. Myeloma was diagnosed when plasma cell infiltrate was greater than 10% on bone marrow aspirate with a paraprotein and or lytic lesions. Eosinophil infiltration did not correlate with any of the tumour clinicopathological markers but showed an inverse correlation with degree of plasmacytosis. Eosinophils were hardly ever found in marrow aspirates that had over 70% plasma cells. They were usually found in trephine sections of bone marrow in areas where there was Grade I/II fibrosis and were often found in close proximity to focal areas of plasma cell infiltration. Whether eosinophils play a role in preventing or maintaining malignant plasma cell recurrence is currently being studied. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3858-3858
Author(s):  
Ahmad Jajeh ◽  
Suresh Nukala

Abstract Plasmacytosis is commonly seen in the bone marrow biopsies of patients with acquired immunodefficiency disease AIDS and human HIV virus infection. Polyclonal increase of immunoglobulin is very common. However few cases of plasma cell dyscrasia are reported. The purpose of this abstract is to show our institution experience with plasma cell dyscrasia and HIV infection. For the last ten years ten patients were identified based on bone marrow biopsy, immunoelectophoresis and immunofixation, twenty four hours urine collection and urine electrophoresis and immunofixation. Immuno staining for kappa and lambda light chain to check for clonality were done on four cases. Mean age of patients is 49 years (range 33 to 59 years). Seven were black, two hispanic and one white. Nine were males and one female. All patients had plasmacytosis on bone marrow more than 30% and protiurea of more than one gram. five patients had nephrotic range protien urea. one patient had IgA lambda, one patient had Ig G kappa All patients had low CD4 counts except two patients with CD4 above 200 and have long standing HIV infection. One patient presented with hepatosplenomegally and increased IgM level and waldnestrome looking plasmacytoid lymphocytes. One patient had plasmablast and plasma cells syncitia who had rapidly fatal disease. one patient expired of respiratory failure before treatment. One patient, a female presented with plasma cell leukemia and did respond to Doxil, vincristine and dexamethasone therapy. She is alife. Two other patients with long standing HIV infection and CD4 count above 200 are still alife both patients were treated initially with Thalidomide and dexamethasone with excellent response. one of them failed Thalidomide after more than one year response and currently on his fourth cycle of velcaid (proteosome inhibitor). All patients were not on HIV therapy at time of diagnosis. In conclusion plasma cell dyscrasia with HIV infection do respond to treatment with durable response. Repetetive antigenic stimulation with HIV-1 p24 antigen are the proposed mechnism of oncogenesis.


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