scholarly journals ID: 1075 Concentration and κ/λ ratio of serum free light chain in multiple myeloma patients at Cho Ray Hospital

2017 ◽  
Vol 4 (S) ◽  
pp. 159
Author(s):  
Hoang Cong Phan ◽  
Thang Thanh Phan ◽  
Toan Trong Ho ◽  
Thu Bich Tran ◽  
Thanh Thanh MCB ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Light Chain ◽  
Kidney Failure ◽  
Free Light Chain ◽  
Newly Diagnosed ◽  
Serum Samples ◽  
Cross Sectional ◽  
Female Ratio ◽  
Significant Difference

Introduction: multiple myeloma (MM) is a B cell malignancy which characterized by accumulation of plasmocyte in bone marrow, immunoglobulins and free light chain in serum (sFLC). According to IMMWG (International multiple myeloma working group), sFLC is a criterion in diagnosis of MM. In this study, we investigate the concentration and κ/λ ratio of sFLC in newly diagnosed MM patients at Cho Ray hospital. Methods: cross-sectional study. Serum samples of 36 newly diagnosed MM patients were analyzed by Binding Site Freelite method to measure the amount of κ and λ sFLC.   Results: the median age of 36 MM patients was 61 yrs (41 – 88 yrs), with the male/female ratio was 1.2/1. MM stage III, stage II and stage I accounting for 63.9% (23/36), 27.8% (10/36), and 8.3% (3/36), respectively. Clonal IgG, IgA and IgE MM accounting for 61.1% (22/36), 30.6% (11/36), and 8.3% (3/36), respectively. We reported the median of plasmocyte in 36 cases was 35.4% (95%CI: 27.6 – 43.3). The median of concentration of κ sFLC, λ sFLC, and involved/uninvolved sFLC ratio were 1601.8 mg/L (95%CI: 104.9 – 3098.7), 900.1 mg/L (95%CI: 10.7 – 1789.5), and 191.0 (95%CI: 87.6 – 294.4), respectively. The abnormally high in sFLC concentration was reported in 97.2% MM cases (35/36), in which 55.6% cases (20/36) had increased κ sFLC, 19.4% cases (7/36) had increased λ sFLC, and 22.2% cases (8/36) had increased both κ+λ sFLC concentration. Increased involved/uninvolved sFLC ratio was found in 94.4% MM cases (34/36), in which 36.1% cases (13/36) had sFLC ratio > 100, with all involved sFLC concentration > 100 mg/L. In 3 cases of MM with kidney failure, 2 cases had increased both κ+λ sFLC, 1 case had increased κ sFLC concentration; and all of 3 cases had involved sFLC level > 5300 mg/L with sFLC ratio > 100. No significant difference of sFLC concentration and sFLC ratio among gender, stage of disease, Ig clone, or plasmocyte percent in bone marrow of MM patients. Conclusions: due to the abnormally high of sFLC concentration and sFLC ratio in MM, it is necessary to monitor frequently these parameters during treatment to prevent the risk of kidney failure for patients.

TIMP-1 and TIMP-2 Levels Are Directly Correlated with Neoangiogenesis and Are Prognostic Factors in Multiple Myeloma Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4866-4866
Author(s):  
Luciana Correa Oliveira de Oliveira ◽  
Juliana Alves Uzuelli ◽  
Ana Paula Alencar de Lima Lange ◽  
Barbara Amelia Aparecida Santana-Lemos ◽  
Marcia Sueli Baggio ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Bone Disease ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
The Impact

Abstract Abstract 4866 Background Multiple myeloma (MM) is an incurable malignant disease, characterized by increased angiogenesis in the bone marrow (BM) microenvironment and aberrant BM metabolism. Matrix metalloproteinases (MMP) are a family of zinc-dependent endopeptidases implicated in tumour progression, invasion, metastasis and angiogenesis, via proteolytic degradation of extracellular matrix. MMPs are inhibited by tissue inhibitors of metalloproteinase (TIMP). Although recent studies have implicated MMP 9 in MM bone disease, little is known about the role of the TIMPs. Objectives a) to compare levels of sRANKL, OPG, MMP-2, MMP-9, TIMP-1, TIMP-2, VEGF, bFGF, microvessel density (MVD) between newly diagnosed MM patients and healthy controls; b) to determine the association of these molecules with disease progression, bone disease and neoangiogenesis and c) to evaluate the impact of these variables on survival. Patients and Methods As of July 2009 38 newly diagnosed and untreated multiple myeloma patients were enrolled in the study. The median age was 61years-old (range 39-91) with 24 (63%) males. Patients were diagnosed and categorized according The International Myeloma Working Group criteria and ISS, respectively. Bone involvement was graded according to standard X-ray: patients with no lesions, or with one/ two bones involved or diffuse osteoporosis were classified as low score, whereas patients with lesions in more than two bones or presence of bone fracture were classified as high score. MMP-2 and MMP-9 were determined by PAGE gelatin zymography from plasma as previously described. MMP-9, TIMP-1 and TIMP-2, OPG and sRANKL concentrations were measured by ELISA. The levels of VEGF, bFGF were obtained using cytometric bead array. Ten healthy volunteers were used as controls. Bone marrow MVD measured in hotspots was evaluated in 26 out of 38 patients at diagnosis and 15 patients with Hodgkin Lymphoma stage IA and IIA (used as controls) by staining immunohistochemically for CD34. Comparisons among groups were analyzed by ANOVA and the correlation by the Spearman's correlation coefficient. Cox regression were performed for overall survival (OS) analysis. Results Patients with MM had elevated TIMP-1, TIMP-2 and OPG values compared with controls. No significant difference was found between plasma sRANKL, pro-MMP2, pro-MMP9 and MMP-9 levels. We found that plasma TIMP-1 levels correlated positively with bFGF, VEGF, MVD, beta-2 microglobulin (B2M) and OPG (r: 0.514, p=0,001, r: 0.350, p=0,031; r: 0.610, p<0.0001; r: 0.760, p<0.0001 and r: 0.701, p<0.0001, respectively) and TIMP-2 levels with bFGF, DMV, B2M and OPG (r: 0.512, p=0.002; r: 0.595, p<0.0001; r: 0.587, p<0.0001 and r: 0.552, p<0.0001, respectively). TIMP-1 and TIMP-2 levels correlated with the ISS stage (p<0.0001, p=0.006, respectively). The only variables that correlated with clinical bone disease staging were hemoglobin, B2M and albumin levels, whereas TIMP-1, TIMP-2, bFGF, VEGF and OPG correlated with DMV. On the univariate analyses, age, gender, proMMP2, TIMP-1, TIMP-2, creatinine, B2M and MVD were significantly associated with overall survival. In Cox regression model, TIMP-1, TIMP-2 and B2M levels remained to be significantly associated with OS. In conclusion, our results suggest that TIMP-1 and TIMP-2 levels are strongly associated with neoangiogenesis and are independent prognostic factors in MM. Disclosures No relevant conflicts of interest to declare.

Intact Immunoglobulin or Fragments Thereof Can Be Detected in Urine in a Proportion of Patients with Multiple Myeloma and Are Associated with Reduced Survival At Presentation

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1828-1828
Author(s):  
Heinz Ludwig ◽  
Philip Young ◽  
Dejan Milosavljevic ◽  
Niklas Zojer ◽  
Wolfgang Hübl ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Binding Site ◽  
Light Chain ◽  
Free Light Chain ◽  
Light Chains ◽  
Glomerular Injury ◽  
Female Ratio ◽  
Serum Free ◽  
Serum Free Light Chain

Abstract Abstract 1828 Introduction: Intact immunoglobulin or fragments thereof (intact/fragmented Ig) can be found in the urine due to nephrotic injury or the preferential scavenging of albumin by the renal FcRn receptor leading to immunoglobulin catabolism. Until now the occurrence, frequency and clinical impact of this phenomenon has not been assessed in patients with multiple myeloma (MM). Here we determine the incidence of intact/fragmented Ig in urine and evaluate its prognostic relevance. Patients and Methods: 94 patients with MM, median age 70 years old (range 41–87) with a male / female ratio 28/66, ISS stage I (48), stage II (23), stage III (28), 69 IgG (43 IgGk/26 IgGl) and 25 IgA (15 IgAk/7 IgAl) were enrolled. Serum free light chain concentrations (sFLC) were measured using commercially available immunoassays (Freelite™, The Binding Site, Birmingham, UK) and compared to electrophoresis results (Hydrasys, Sebia, Paris, France). Overall survival was estimated by the product limiting method of Kaplan-Meyer and survival was compared by the log rank test. Results: Overall, sFLC ratios had a greater sensitivity than urine immunofixation (uIFE) for the detection of monoclonal light chains 86/94 vs. 46/94. In 13/46 (28%) uIFE positive patients intact immunoglobulins or significant fragments (intact/fragmented Ig) thereof were detected, 12 IgG, (12/69, 17%) and 1 IgA (1/25, 4%). Three of these patients had normal urine protein concentrations (<250mg/L) and 2/13 patients had glomerular injury identified by increased levels of albumin excretion. There was no difference in creatinine levels between patients with or without intact/fragmented Ig (p=0.673). Analysis of overall survival in patients stratified at presentation according to uIFE results, namely the presence of intact/fragmented Ig, abnormal serum free light chain ratio-, and negative uIFE results revealed significantly shorter overall survival for the intact/fragmented Ig group (median OS: 34.5 vs. 66.0, vs. 80.6 months, respectively, p< 0.048) (figure 1). Discussion: Our findings confirm the superiority of the serum free light chain assay for detection of monoclonal free light chains as compared to urine immunofixation. However, the serum free light chain assay is inadequate for detection of intact/fragmented Ig in urine. The most important finding presented here is the observation that intact and/or fragment immunoglobulin is present in a substantial number of patients with MM. This phenomenon is mainly restricted to IgG isotypes. There are two possible explanations for these findings: first, the presence of glomerular injury, but this phenomenon (increased albumin leakage) was only seen in two patients and hence is unlikely to account for this observation. The second explanation relies upon disruption of the FcRn receptor function in immunoglobulin scavenging. This receptor will preferentially scavenge albumin in the renal setting, but dysfunction may lead to increased immunoglobulin catabolism and the presence of intact and/or fragmented Ig (Sarav, JASN, 20: 1941–1952, 2009). The results may reflect a hitherto unidentified subtle renal dysfunction. In line with this notion overall survival in our patients intact/fragmented Ig was found to be significantly shorter. Conclusion: We observed an unexpected high incidence of intact/fragmented Ig in the urine of our patients with MM. Patients with urinary excretion of intact/fragmented immunoglobulin had significantly shorter survival. These findings should be validated in further studies. Disclosures: Young: Binding Site: Employment. Harding:Binding Site: Employment.

scholarly journals CD43 Expression Is an Adverse Prognostic Factor in Newly Diagnosed Multiple Myeloma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4753-4753
Author(s):  
Xueqin Ning ◽  
Yongqiang Wei ◽  
Xiaolei Wei ◽  
Ru Feng ◽  
Bingyuan Chen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Prognostic Factor ◽  
Plasma Cells ◽  
Newly Diagnosed ◽  
Negative Group ◽  
Hematopoietic Stem ◽  
Female Ratio ◽  
Positive Group ◽  
Adverse Prognostic Factor

Abstract CD43 expression is an adverse prognostic factor in newly diagnosed multiple myeloma Introduction CD43 is an abundant, heavily-glycosylated, cell surface protein expressed on bone marrow hematopoietic stem cells and most white blood cells. Previous studies have found that CD43 also expressed in some types of lymphoma cells and associated with adverse outcomes. However, the prognosis value of CD43 expression in multiple myeloma (MM) remain unknown. Patients and Methods A total of 109 MM patients, newly diagnosed in Nanfang Hospital of Southern Medical University from January 2017 to December 2019, were included in the study. CD43 was detected by flow cytometre as follows: 2 ml of heparin anticoagulated bone marrow was collected from the patients at the time of diagnosis，1×10 6 cells were detected, and a gate was set for identifying abnormal plasma cells characterized by CD138 expression and CD38. CD43 positive was defined as more than 20% of the plasma cells expressed CD43. Results A total of 109 patients with newly diagnosed MM were enrolled in the study, including 77 patients (70.6%) for CD43 positive and 32 patients (29.4%) for CD43 negative . The median age was 58 years, and the male-female ratio was 1.7:1. Patients in the CD43 positive group were more likely to have international staging system (ISS) stage III (67.5% VS 46.9%, P= 0.044), hemoglobin &lt; 85g/L (64.9% VS 37.5%, P= 0.008), 13q deletion (31.4% VS 10.4%), and higher percentage of bone marrow monoclonal plasma cells detected by flow cytometry (5.5% VS 1.4%, P=0.003). Most patients enrolled in the study received bortezomib-based treatment. The very good partial response (VGPR) or better rate after 4 induction cycles was significantly lower in the CD43 positive group than CD43 negative group (35.1% VS 56.3%, P=0.041), and the overall response rate (ORR) in the CD43 positive group was lower than that in CD43 negative group (75.3% VS 84.4%, P=0.299), but no significantly difference. The median follow-up time was 22 months. Patients with CD43 positive had significantly lower PFS (median PFS 24 months VS not reached, P =0.012), and OS (median OS not reached, P = 0.023) than those with CD43 negative. Multivariate analysis indicated that CD43 positive expression was an independent poor risk factor for PFS (HR 2.517 95%CI 1.178-5.376, P = 0.017) and OS (HR 3.664 95%CI 1.100-12.075, P = 0.034). Conclusion Our study showed that CD43 expression was an adverse prognosis for multiple myeloma. Disclosures No relevant conflicts of interest to declare.

Anti-Angiogenic Effect of Bortezomib in Multiple Myeloma Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4912-4912
Author(s):  
Marianna Politou ◽  
Kikeri Naresh ◽  
Evangelos Terpos ◽  
Danielle Crowley ◽  
Irvin Lambert ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Partial Response ◽  
Angiogenic Factors ◽  
Response To Treatment ◽  
Serum Samples ◽  
Bone Marrow Biopsies ◽  
Significant Difference ◽  
Before And After ◽  
Angiogenic Effect

Abstract Bortezomib is a proteasome inhibitor, which is an effective treatment for multiple myeloma (MM). Bortezomib inhibits NF-κB and thus enhances apoptosis and leads to reduced levels of growth factors, angiogenic factors and cell adhesion molecules, which are crucial for the growth and survival of myeloma. The aim of this study was to investigate whether bortezomib has an anti-angiogenic effect in MM patients and whether that effect correlates with response to treatment. We have studied the effect of bortezomib on angiogenesis in bone marrow biopsies and serum samples of nine patients with MM, who were treated with bortezomib. The patients studied (6M/3F median age 59 years, range 35–71 years) had received more than 4 lines of treatment before bortezomib administration. Six patients had IgG, one IgA, one non-secretory and one light-chain MM. Bortezomib was given at a dose of 1.3 mg/m2, iv, in 3-week cycles, on days 1, 4, 8, and 11 of each cycle. Microvessel density (MVD) was assessed in bone marrow trephine biopsies before and after 8 cycles of treatment by immunohistochemistry with monoclonal mouse antibodies to CD34 (QBEND-10, DAKO, Denmark). Serum samples were assessed for VEGF and angiogenin levels before and after every cycle of treatment with an ELISA (R&D systems). Five out of 9 patients achieved a partial response (PR), two patients had a minimal response (MR),one achieved a good partial response (GPR) and one a complete response (CR) to bortezomib administration, according to EBMT criteria. In six out of 9 patients there was a decrease of the MVD. More specifically in two of the patients with PR (P2,P4) and the two patients with MR (P5 and P7) there was a significant decrease in the MVD ( 1.7, 3.8, 4.2 and 1.4 fold decrease respectively). Patient 9, who achieved GPR had also a 2.3 fold decrease in MVD. In patients P2,P4,P5 and P6, who received 8 cycles of treatment, further reduction of MVD was noticed with further treatment. In patient 1, who achieved a PR, MVD did not show any significant change after 8 cycles of treatment. The patient relapsed soon after he has completed the treatment. In patient 5, the MVD increased over 2-fold and she relapsed very soon after the 4th cycle and died of disease progression. There was a significant reduction in mean angiogenin levels by cycle 4 (380 ng/ml) when compared with cycle 1 (537ng/ml) (p=0.028). On the contrary, there was no significant difference between the levels of VEGF at cycles 1 and 4 (122.5 pg/ml and 127.2 pg/ml respectively) (p=0.173).All data are shown in Table 1. We conclude that PS-341 may exert its anti-myeloma effect partly through anti- angiogenic mechanisms. Whether Bortezomib acts directly on endothelial cells or indirectly through modulation of the expression of angiogenic factors and angiopoetins which influence endothelial cell proliferartion and survival is unclear. Before treatment After 4th Cycle of treatment After 8th Cycle of treatment response to treatment VEGF(pg/ml)/Ang (ng/ml) MVD vessels/mm 2 VEGF(pg/ml)/Ang (ng/ml) MVD vessels/mm 2 VEGF(pg/ml)/Ang (ng/ml) MVD vessels/mm 2 patient 1 PR 213/642 74.1 813/432 428/361 83.99 Patient 2 PR 172/425 124.7 449/334 77.48 243/371 73.85 patient 3 PR 84/404 61/256 175/2 65 patient 4 PR 160/800 109.55 180/316 37.5 80/359 28.5 patient 5 MR 57/615 195.8 70/517 85.51 94/447 46.1 patient 6 PR 47/459 267 82/335 591.8 patient 7 MR 105.88 75.55 patient 8 GPR 48.89 2 patient 9 CR 135.78 57.14

Superior Rate of Complete Response with up-Front Velcade-Thalidomide-Dexamethasone Versus Thalidomide-Dexamethasone in Newly Diagnosed Multiple Myeloma Is Not Affected by Adverse Prognostic Factors, Including High-Risk Cytogenetic Abnormalities.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1662-1662
Author(s):  
Michele Cavo ◽  
Nicoletta Testoni ◽  
Carolina Terragna ◽  
Giulia Marzocchi ◽  
Sandra Durante ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
High Risk ◽  
Light Chain ◽  
Complete Response ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Cox Regression Analysis

Abstract Complete response (CR) is an important objective of autologous stem-cell transplantation (ASCT) in multiple myeloma (MM). In comparison with conventional induction treatments, newer combinations of novel agents may effect increased rates of CR and near CR (nCR), a benefit potentially translating into even higher frequencies of CR/nCR after ASCT and improved clinical outcome. We designed a phase III study to detect an increase in CR+nCR rates from 10–15% with conventional Thalidomide-Dexamethasone (TD) to 20–30% with Velcade added to TD (VTD) in newly diagnosed MM. Both TD and VTD were given as three 21-day cycles in preparation for double ASCT. In the present analysis, CR+nCR rates by the two induction treatments were examined in relationship to baseline prognostic variables in 399 evaluable pts aged ≤65 years, of whom 199 randomized to VTD and 200 to TD. All analyses were intent to treat. In comparison with TD, VTD effected higher rates of CR+nCR (12% vs 33%, P&lt;0.001) and of ≥very good partial response (VGPR) (30% vs 61%, P&lt;0.001). By univariate analysis, superiority of VTD to TD was maintained across all sub-group analyses according to standard prognostic factors, including β2-m, albumin, stage (ISS), Hb, PLTs, bone marrow PC, M protein isotype, LDH, CRP. In particular, the rates of CR+nCR with VTD vs TD in pts with standard poor prognostic factors were as follows: ISS stage 3 (23.5% vs 6%, P=0.03), Hb&lt;10 g/dL (24% vs 4%, P=0.002), PLTs&lt;150.000/μL (35% vs 4%, P=0.009), bone marrow PC ≥50% (31% vs 13%, P&lt;0.001), IgA isotype (63% vs 15%, P&lt;0.001), LDH &gt;190 U/L (33% vs 9%, P&lt;0.001), CRP ≥8 mg/L (29% vs 10%, P=0.004). We next examined CR+nCRs by treatment arms in relationship to cytogenetics (FISH data available in 93% to 99% of all pts). Superior CR+nCR rates were effected by VTD vs TD in the presence of high-risk cytogenetics, including del(13) (39% vs 10%, P&lt;0.001), t(4;14) (39.5% vs 10%, P=0.002), combined t(4;14) and del(13) (32% vs 0%, P=0.001), and del(17p) (28.5% vs 0%, P=0.03). Remarkably, when examined in the context of the VTD arm, high-quality response rates were significantly higher for pts carrying del(13) and t(4;14) vs those who lacked these abnormalities [del(13): CR+nCR:39% vs 24%, P=0.03; ≥VGPR: 71% vs 48%, P=0.001] [t(4;14): ≥VGPR:79% vs 55%, P=0.007)]. An opposite trend was noted for pts in the TD arm, whose probability to attain ≥VGPR was adversely affected by the presence of del(13) (P=0.07) and del(17p) (P=0.03). Variables associated with achievement of CR+nCR in the two arms that retained statistical significance when assessed by multivariate Cox regression analysis included randomization to VTD (P&lt;0.001), light chain only subtype (P&lt;0.001), IgA isotype (P&lt;0.001) and Hb&gt;10 g/dL (P=0.01). In the VTD arm, a positive correlation was observed with del(13) (P=0.006) and t(4;14) (P=0.02). Response to first ASCT with melphalan 200 mg/m2 could be evaluated in 297 pts, of whom 145 randomized to VTD and 152 to TD. Randomization to VTD was closely associated with increased CR+nCR rates (54% vs 29% with TD, P&lt;0.001) and remained statistically significant (P&lt;0.001) also in the multivariate analysis. Additional factors predicting for superior post-ASCT CR+nCR rates in the multivariate setting included light chain only subtype (P&lt;0.001) and IgA isotype (P=0.005). We conclude that randomization to up-front VTD was the strongest and independent factor associated with increased rates of CR+nCR before ASCT. Superiority of VTD to TD pertained in both low-risk and high-risk sub-groups, including the traditionally unfavorable sub-groups carrying del(13), t(4,14) and del(17p). Remarkably, in the VTD arm improved postinduction CR+nCR rates were significantly associated with the presence of del(13) and t(4;14) in the multivariate analysis. Benefit from VTD vs TD as primary induction therapy translated into significantly improved CR+nCR rates after the first ASCT and remained statistically significant when assessed by multivariate analysis.

Immunoglobulin Free Light Chain Ratio Is an Independent Risk Factor for Progression of Smoldering Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1487-1487 ◽  
Author(s):  
Angela Dispenzieri ◽  
Robert A. Kyle ◽  
Jerry A. Katzmann ◽  
Dirk Larson ◽  
Joanne Benson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Light Chain ◽  
Plasma Cells ◽  
Free Light Chain ◽  
M Protein ◽  
Baseline Serum ◽  
Smoldering Multiple Myeloma ◽  
Risk Of Progression ◽  
Bone Marrow Plasma

Abstract Background: Smoldering multiple myeloma (SMM) is an asymptomatic plasma cell proliferative disorder with a high risk of progression to symptomatic multiple myeloma. Identification of risk factors that predict progression of SMM to symptomatic MM could identify higher risk patients who might benefit from chemoprevention or more intensive surveillance. We hypothesized that increased monoclonal free kappa or lambda immunoglobulin light chains in smoldering myeloma (SMM), as detected by the serum free light chain (FLC) assay, indicates an increased the risk of progression to active myeloma. Methods: Of 276 pathologically confirmed SMM patients seen at the Mayo Clinic from 1970 to 1995, baseline serum samples obtained within 30 days of diagnosis were available in 273. Results: At a median follow-up of surviving patients of 12.4 years, transformation to active disease has occurred in 161 (59%) patients. An abnormal FLC ratio was present at baseline in 90% of patients. The best break-point for predicting risk of progression was a FLC ratio less than or equal to 0.125 or greater than or equal to 8 (hazard ratio, 2.3; 95% CI, 1.6–3.2) [Figure 1]. The extent of abnormality of FLC ratio was independent of SMM risk categories defined by number of plasma cells in the bone marrow and size of serum M-proteins (bone marrow plasma cells ≥ 10% and serum M protein ≥ 3 g/dL; bone marrow plasma cells ≥ 10% but serum M protein &lt; 3 g/dL; and serum M protein ≥ 3 g/dL but bone marrow plasma cells &lt; 10%). Incorporating the FLC ratio into the risk model, the division of patients into high-, intermediate-, and low-risk groups is 28, 42, and 30% with 5 year progression rates of 76, 51, and 25%, respectively [Figure 2]. Conclusions: The serum immunoglobulin FLC ratio is an important additional determinant of clinical outcome in patients with SMM. Figure Figure Figure Figure

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