Presence of an Abnormal Serum Free Light Ratio Is an Independent Risk Factor for Progression in Monoclonal Gammopathy of Undetermined Significance (MGUS).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3647-3647
Author(s):  
S. Vincent Rajkumar ◽  
Robert A. Kyle ◽  
Terry M. Therneau ◽  
L. Joseph Melton ◽  
Arthur R. Bradwell ◽  
...  

Abstract Background: Monoclonal gammopathy of undetermined significance (MGUS) affects 3% of persons age 50 yrs or greater. Reliable predictors of progression of MGUS to myeloma or related malignancy are needed. We hypothesized that the presence of monoclonal unbound (free) kappa or lambda immunoglobulin light chains in MGUS, as detected by an abnormal serum kappa/lambda free light chain (FLC) ratio would indicate clonal evolution in the neoplastic plasma cell and increase risk of progression to malignancy. Methods: Patients (pts) from Southeastern Minnesota with MGUS seen at the Mayo Clinic from Jan 1, 1960 through Dec 31, 1994 who had baseline serum samples collected and stored at the time MGUS was first recognized were studied. Free kappa and lambda chains were measured using the serum FLC assay (FREELITETM, The Binding Site Ltd). Results: Of 1384 pts with MGUS during the defined time period, baseline serum samples obtained within 30 days of diagnosis of MGUS were available in 1148 pts. At a median follow-up of 15 yrs, malignant progression has occurred in 87 (7.6%) pts: myeloma (53 pts), IgM lymphoma (17), primary amyloidosis (6), macroglobulinemia (6), chronic lymphocytic leukemia (3) and plasmacytoma (2). An abnormal kappa/lamda FLC ratio (kappa/lambda ratio <0.26 or >1.65) indicating presence of monoclonal FLC was detected in 379 (33%) pts. In a Cox proportional hazards model, the risk of progression in pts with an abnormal kappa/lamda FLC ratio was significantly higher (hazard ratio 3.5, 95% CI 2.3–5.5; p<0.001) compared to pts with a normal ratio. After adjusting for the size of the serum monoclonal (M) protein by multivariate analysis, the hazard ratio was only slightly reduced to 2.8, p<0.001. The risk of progression to myeloma or related malignancy at 10 years was 17% with an abnormal kappa/lambda FLC ratio versus 5% with a normal ratio; corresponding rates at 20 years were 35%, and 13%, respectively. MGUS pts with both an abnormal serum FLC ratio and high serum M protein had a risk of progression at 20 years of 46% (high-risk), versus 26% with one of two risk factors (intermediate-risk) and 7% with no risk factors (low-risk) (Table). The true life-time (28 year) risk of myeloma or related malignancy in the low-risk group was only 5.3% when other competing causes of death were taken into account. Conclusions: Presence of monoclonal FLC in the serum as detected by an abnormal kappa/lamda FLC ratio is a major independent risk factor for progression of MGUS to myeloma or a related malignancy. The new risk-stratification identifies a low-risk subset with a remarkably small life-time risk of progression, a finding of significant importance for the management of MGUS. Risk-stratification of MGUS using the size of the serum M spike and free light chain ratio Risk Group No. of patients Hazard ratio Absolute risk of progression at 20 years Low-risk (Serum M protein <1.5 gm/dL and normal FLC ratio [0.26–1.65]) 606 1 7% Intermediate-risk (Either risk factor present) 373 3.5 26% High-risk (Serum M protein >/=1.5 gm/dL and abnormal FLC ratio [<0.26 or >1.65]) 169 6.8 46%

Blood ◽  
2008 ◽  
Vol 111 (2) ◽  
pp. 785-789 ◽  
Author(s):  
Angela Dispenzieri ◽  
Robert A. Kyle ◽  
Jerry A. Katzmann ◽  
Terry M. Therneau ◽  
Dirk Larson ◽  
...  

We hypothesized that increased monoclonal free kappa or lambda immunoglobulin light chains in smoldering multiple myeloma (SMM), as detected by the serum free light chain (FLC) assay, indicates an increased risk of progression to active myeloma. Baseline serum samples obtained within 30 days of diagnosis were available in 273 patients with SMM seen from 1970 to 1995. At a median follow-up of surviving patients of 12.4 years, transformation to active disease has occurred in 59%. The best breakpoint for predicting risk of progression was an FLC ratio of 0.125 or less, or 8 or more (hazard ratio, 2.3; 95% CI, 1.6-3.2). The extent of abnormality of FLC ratio was independent of SMM risk categories defined by number of bone marrow plasma cells (BMPCs) and size of serum M proteins (BMPC ≥ 10% and serum M protein ≥ 3 g/dL; BMPC ≥ 10% but serum M protein < 3 g/dL; and serum M protein≥ 3 g/dL but BMPC < 10%). Incorporating the FLC ratio into the risk model, the 5-year progression rates in high-, intermediate-, and low-risk groups were 76%, 51%, and 25%, respectively. The serum immunoglobulin FLC ratio is an important additional determinant of clinical outcome in patients with SMM.


Blood ◽  
2006 ◽  
Vol 108 (6) ◽  
pp. 1979-1983 ◽  
Author(s):  
David Dingli ◽  
Robert A. Kyle ◽  
S. Vincent Rajkumar ◽  
Grzegorz S. Nowakowski ◽  
Dirk R. Larson ◽  
...  

AbstractAn abnormal serum immunoglobulin free light chain (FLC) ratio at diagnosis may identify risk of progression to myeloma in patients with solitary bone plasmacytoma (SBP). In the cohort of 116 patients, 43 have progressed to myeloma, with a median time to progression of 1.8 years. The FLC ratio was determined in all 116 patients on serum collected at time of diagnosis and was abnormal in 54 patients (47%). An abnormal FLC ratio was associated with a higher risk of progression to myeloma (P = .039). The risk of progression at 5 years was 44% in patients with an abnormal serum FLC ratio at diagnosis compared with 26% in those with a normal FLC ratio. One to 2 years following diagnosis, a persistent serum M protein level of 5 g/L (0.5 g/dL) or higher was an additional risk factor for progression. A risk stratification model was constructed using the 2 variables of FLC ratio and M protein level: patients with a normal FLC ratio at baseline and M protein level less than 5 g/L (0.5 g/dL) at 1 to 2 years following diagnosis (low risk, n = 31); with either risk factor abnormal (intermediate risk, n = 26); and with both an abnormal FLC ratio and M protein level of 5 g/L (0.5 g/dL) or higher (high risk, n = 18). The corresponding progression rates at 5 years were significantly different in the low, intermediate, and high groups: 13%, 26%, and 62%, respectively (P < .001).


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3376-3376 ◽  
Author(s):  
Viera Sandecka ◽  
Zdenek Adam ◽  
Ivan Spicka ◽  
Vlastimil Scudla ◽  
Evzen Gregora ◽  
...  

Abstract Introduction: Monoclonal gammopathy of undetermined significance (MGUS) is a non-malignant condition associated with a risk of progression to multiple myeloma (MM) or related disorders. There are currently 2 clinical models predicting progression from MGUS to MM. The Mayo Clinic model uses levels and type of serum monoclonal protein (M-protein) and serum free light chain ratio (sFLC). The Spanish PETHEMA model uses flow cytometry of bone marrow plasmocytes (BMPC) and the presence of DNA aneuploidy. Purpose: The primary end point was to estimate the cumulative risk of hematologic disorders occurring during the follow-up of our cohort. The secondary end points were: to validate known clinical models suggested by the Mayo Clinic group and the Spanish PETHEMA group for the risk of progression from MGUS to MM or related malignancies and to establish a new risk model by the Czech Myeloma Group (CMG model) with better prediction of low-risk MGUS group. Group: Data for this study were obtained from the Registry of Monoclonal Gammopathies (RMG) acquired from hematologic centers of the Czech Republic. MGUS diagnosis was made according to IMWG criteria. In total, 2028 persons with MGUS were enrolled in the RMG study from May 2007 to June 2013. A total of 93% (1887/2028) of persons were evaluated. Results: 1887 MGUS persons were followed with median 4 years. Malignancies developed in 8.6% (162/1887) cases; MM occurred in 77.2% (125/162) of persons. The risk of progression was 1.5% at 1 year, 7.6% at 5 years and 16.5% at 10 years after diagnosis. The key predictors factors of progression were as follows: age ≥ 69 years, serum M- protein concentration ≥ 1.5 g/dL, BMPC > 5%, pathological sFLC ratio (< 0.26 or >1.65), immunoparesis of polyclonal immunoglobulins, levels of serum hemoglobin at baseline < 12.0 g/dL and the presence of normal plasma cells (nPC) in bone marrow ≤ 5 % identified by multiparametric flow cytometry techniques. Distribution of MGUS persons according to risk groups based on the Mayo Clinic model confirmed predictive power of Mayo Clinic model based on our data although isotype of M- protein was not found as independent predictor. At 10 years, no-risk group had 4.9% risk of progression compared to 16.3%, 24.6%, and 54.9% in groups with 1, 2 or 3 risk factors, respectively (p< 0.001). MGUS group with 1, 2 and 3 risk factors in comparison to the reference group without any risk factor had HR( 2.59 [95% CI: 1.39- 4.84]; p= 0.003, HR 4.79 [95% CI: 2.56-8.93]; p< 0.001, HR 12.97 [95% CI: 5.52-30.48];p< 0.001), retrospectively. Immunoparesis instead of DNA aneuploidy was used together with the presence of abnormal plasma cells (aPCs) to validate the modified PETHEMA model. The rates of progression at 3 years were 2.5%, 8.1% and 28.0% for groups with neither, one or both risk factors, respectively (p< 0.001). MGUS group with 1 and 2 risk factors in comparison to the reference group without any risk factor had HR (3.98 [95% CI: 1.60-9.91]; p= 0.003, HR 14.23 [95% CI: 2.86-70.76]; p< 0.001), retrospectively. Based on the 5 parameters with independent predictive value in the univariate analysis (immunoparesis, serum M-protein quantity ≥ 1.5 g/dL, BMPC > 5%, abnormal sFLC ratio and serum level of hemoglobin < 12.0 g/dL) we proposed a new CMG model. The created CMG model clearly detected MGUS persons at low risk 86.6% (828/956) with the risk of progression 5.6% at 5 years better than previously described models. As expected, the number of MGUS persons with the highest risk of progression was limited to 3.7% only (35/956), with the risk of progression 31.9% at 5 years. The MGUS group with 5 risk factors had 63 times higher hazard of progression compared to reference MGUS group (HR 63.17 [95% CI: 13.99-285.36]; p< 0.001). Conclusion: In the large cohort of MGUS persons, we confirmed validity of previously considered clinical models for the risk of progression from MGUS to MM by the Mayo Clinic group and the Spanish PETHEMA group (model used for SMM). New CMG model for the risk of progression from MGUS to MM or related malignancies was established with an advantage for better identification of MGUS persons at low risk (87% of persons with risk of progression below 10% in 5 years) as well as few persons at the highest risk of progression. As a consequence, limited evaluation and visits can be planned in majority of MGUS persons in follow-up. Acknowledgments: This work was supported by grants NT13492-4, NT14575-3 and by EU FP7/2007-2013; grant n° 278570. Disclosures No relevant conflicts of interest to declare.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20502-e20502
Author(s):  
D. Warr ◽  
J. C. Street ◽  
A. D. Carides

e20502 Background: Age, alcohol use, and history of sickness associated with pregnancy or motion have been identified as risk factors for chemotherapy-induced emesis. This post hoc analysis addressed two questions: 1) Can prognostic factors identify a low risk group for whom ondansetron (OND) plus dexamethasone [D] alone provide a high level of protection (≥80% no emesis)? 2) Does the NK1 receptor antagonist aprepitant improve antiemetic outcome regardless of emetic risk? Methods: The analysis was based upon outcomes in patients with breast cancer enrolled in a Phase III double-blind, placebo-controlled trial randomized to Day 1 OND 8 mg and D 20 mg before chemotherapy and OND 8 hours later and OND 8 mg bid Days 2–3 vs. Day 1 aprepitant 125 mg PO, OND 8 mg, and D 12 mg before chemotherapy and OND 8 mg 8 hours later and aprepitant 80 mg PO qd Days 2–3. Multivariate logistic regression models were used to assess the impact on emesis of the regimen with aprepitant, and previously reported risk factors, including age (<55 and ≥55 years), ethanol use (0–4 or ≥5 drinks/week), history of pregnancy-related morning sickness, and history of motion sickness, using a modified intent-to-treat approach. Results: 856 patients were assessed for efficacy. Treatment with aprepitant (p<0.0001), older age (p=0.006), ethanol use (p=0.0048), and no history of morning sickness (p=0.0007) were all significantly associated with reduced likelihood of emesis; motion sickness was not a risk factor. The Table below shows the probability of no emesis associated with the presence of 0, 1, 2, or all of these factors in the aprepitant and active control arms. Conclusions: 1) The low-risk group identified by this analysis is of questionable utility because it comprised less than 3% of patients. 2) We could not confirm that motion sickness was a significant risk factor. 3) Aprepitant improved the control of emesis irrespective of the number of risk factors for emesis. [Table: see text] [Table: see text]


2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Safaa S. Imam ◽  
Rania A. El-Farrash ◽  
Hesham M. Taha ◽  
Helbees E. Bishoy

Aim. To compare targeted neonatal hearing screening (TNHS) and universal neonatal hearing screening (UNHS) since many developing countries, including Egypt, implement selective screening for high-risk neonates. Methods. 150 neonates were assessed; 50 full terms consecutively admitted to the well-baby nursery and 100 neonates consecutively admitted to neonatal intensive care unit (NICU), Ain Shams University. Patients were further subdivided into high-risk group which included 50 neonates with multiple risk factors for hearing loss and low risk group which included 50 neonates with only one risk factor. Transient evoked otoacoustic emissions (TEOAEs) were used for hearing screening. Auditory brain response (ABR) was performed 3 months later for failed TEOAEs. Results. The most frequent risk factor was consanguinity (46%). In the well-baby population, 16% failed TEOAEs. In the NICU, 30% of the low risk and 38% of the high risk groups failed TEOAEs. Regarding ABR, failed results were 12%, 10%, and 8% in the high-risk, low-risk, and healthy groups, respectively. Conclusion. The use of TNHS would have missed 8% of neonates from the well-baby group who actually had PCHL (permanent congenital hearing loss). The use of UNHS would identify all cases with PCHL, allowing for early intervention and follow-up.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1987-1987
Author(s):  
Akhil Chopra ◽  
Nina D’Abreo ◽  
Gayathri Nagaraj ◽  
Raid Aljumaily ◽  
Michael Styler ◽  
...  

Abstract Mortality rates after allogeneic hematopoietic cell transplantation for hematological malignancies remains high. Recently, a 50-point pretransplantation assessment of mortality (PAM) score was developed by clinical investigators at the Fred Hutchison Cancer Research Center utilizing eight pre-transplant clinical variables including age, donor type, disease risk, conditioning regimen, percentage of predicted FEV1, percentage of predicted DLCO, serum creatinine level and serum ALT level. The PAM score performed well to predict risk of death in the first two years after allogeneic hematopoietic cell transplantation. The objective of our study was to validate the PAM score in a retrospective cohort of patients that underwent allogeneic hematopoietic cell transplantation at Hahnemann University Hospital from 1986 until 2006. 400 patients underwent allogeneic hematopoietic cell transplantation from 1986 to 2006. 170 patients were found to be eligible for retrospective analysis since pre- transplant serum alanine aminotransferase (ALT) levels were not available for the remaining 230 patients. The PAM score was calculated for each patient using the scoring system outlined in the original article. The patients were categorized into four cohorts with scores ranging from 9 to 16 for category 1 (probability of death, 25%), from 17 to 23 for category 2 (probability of death, 25% to 50%), from 24 to 30 for category 3 (probability of death, 50% to 75%), and from 31 to 44 for category 4 (probability of death, 75%). Kaplan- Meier survival curves were generated for each of the four categories. Overall mortality was 62.9% at 2 years. PAM scores ranged from 11 to 36. 41 patients were grouped into category 1, 71 into category 2, 48 patients into category 3 and 10 patients into category 4. Mortality at 2 years was 39% in category 1, 56.3% in category 2, 85.4% in category 3 and 100% in the high-risk category. Compared to the low risk group, group 2 had a hazard ratio of 1.64 (p = 0.092, CI: 0.92 to 2.94); group 3 had a hazard ratio of 3.996 compared to the low risk group (p &lt; 0.001, CI: 2.23 to 7.16) and group 4 had a hazard ratio of 6.73 versus the low-risk group (p &lt; 0.001, 95% CI: 3.01 to 15.04). In conclusion, the PAM score successfully classified patients into distinct survival groups (p &lt; 0.001 for the comparison by log-rank test). Higher PAM scores were associated with progressively increased risk of death. Figure Figure


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1487-1487 ◽  
Author(s):  
Angela Dispenzieri ◽  
Robert A. Kyle ◽  
Jerry A. Katzmann ◽  
Dirk Larson ◽  
Joanne Benson ◽  
...  

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


Blood ◽  
2005 ◽  
Vol 106 (3) ◽  
pp. 812-817 ◽  
Author(s):  
S. Vincent Rajkumar ◽  
Robert A. Kyle ◽  
Terry M. Therneau ◽  
L. Joseph Melton ◽  
Arthur R. Bradwell ◽  
...  

AbstractWe hypothesized that the presence of monoclonal free kappa or lambda immunoglobulin light chains in monoclonal gammopathy of undetermined significance (MGUS), as detected by the serum free light chain (FLC) assay increases the risk of progression to malignancy. Of 1384 patients with MGUS from Southeastern Minnesota seen at the Mayo Clinic from 1960 to 1994, baseline serum samples obtained within 30 days of diagnosis were available in 1148. At a median follow-up of 15 years, malignant progression had occurred in 87 (7.6%) patients. An abnormal FLC ratio (kappa-lambda ratio &lt; 0.26 or &gt; 1.65) was detected in 379 (33%) patients. The risk of progression in patients with an abnormal FLC ratio was significantly higher compared with patients with a normal ratio (hazard ratio, 3.5; 95% confidence interval [CI], 2.3-5.5; P &lt; .001) and was independent of the size and type of the serum monoclonal (M) protein. Patients with an abnormal serum FLC ratio, non–immunoglobulin G (non-IgG) MGUS, and a high serum M protein level (≥ 15 g/L) had a risk of progression at 20 years of 58% (high-risk MGUS) versus 37% with any 2 of these risk factors (high-intermediate risk), 21% with one risk factor (low-intermediate risk), and 5% when none of the risk factors were present (low risk).


2020 ◽  
Vol 11 ◽  
pp. 215013272098129
Author(s):  
Lauren Oshman ◽  
Amanda Caplan ◽  
Raabiah Ali ◽  
Lavisha Singh ◽  
Rabeeya Khalid ◽  
...  

Introduction: The CDC and Illinois Department of Public Health disseminated risk factor criteria for COVID-19 testing early in the pandemic. The objective of this study is to assess the effectiveness of risk stratifying patients for COVID-19 testing and to identify which risk factors and which other clinical variables were associated with SARS-CoV-2 PCR test positivity. Methods: We conducted an observational cohort study on a sample of symptomatic patients evaluated at an immediate care setting. A risk assessment questionnaire was administered to every patient before clinician evaluation. High-risk patients received SARS-CoV-2 test and low-risk patients were evaluated by a clinician and selectively tested based on clinician judgment. Multivariate analyses tested whether risk factors and additional variables were associated with test positivity. Results: The adjusted odds ratio of testing positive was associated with COVID-19-positive or suspect close contact (aOR 1.56, 95% CI 1.15-2.10), large gathering attendance with a COVID-19-positive individual (aOR 1.92, 95% CI 1.10-3.34), and, with the largest effect size, decreased taste/smell (aOR 2.83, 95% CI 2.01-3.99). Testing positive was associated with ages 45-64 and ≥65 (aOR 1.75, 95% CI 1.25-2.44, and aOR 2.78, 95% CI 1.49-5.16), systolic blood pressures ≤120 (aOR 1.64, 95% CI 1.20-2.24), and, with the largest effect size, temperatures ≥99.0°F (aOR 3.06, 95% CI 2.23-4.20). The rate of positive SARS-CoV-2 test was similar between high-risk and low risk patients (225 [22.2%] vs 50 [19.8%]; P = .41). Discussion: The risk assessment questionnaire was not effective at stratifying patients for testing. Although individual risk factors were associated with SARS-CoV-2 test positivity, the low-risk group had similar positivity rates to the high-risk group. Our observations underscore the need for clinicians to develop clinical experience and share best practices and for systems and payors to support policies, funding, and resources to test all symptomatic patients.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3493-3493 ◽  
Author(s):  
Robert Kyle ◽  
Terry Therneau ◽  
Angela Dispenzieri ◽  
Dirk Larson ◽  
Matthew Plevak ◽  
...  

Abstract Chronic Idiopathic Bence Jones Proteinuria (first reported in 1982) is an asymptomatic plasma cell proliferative disorder that is associated with a risk of progression to symptomatic multiple myeloma (MM) or primary amyloidosis (AL). We defined it as the presence of a monoclonal light chain in the urine, absence of an intact immunoglobulin M protein (IgH expression) in the serum, fewer than 10% bone marrow plasma cells (if done), and no evidence of MM, AL or other related plasma cell proliferative disorders. Following approval by the Mayo Clinic Institutional Review Board, we searched a computerized database and reviewed the records of all patients who were seen at Mayo Clinic within 30 days of the recognition of a monoclonal light chain (Bence Jones protein) in the urine between 1960 and 1996. Patients found to have end-organ damage at diagnosis as the result of the plasma cell proliferative disorder (including MM or AL), received chemotherapy, or had a nephrotic syndrome were excluded. Follow-up included review of each subject’s medical record at Mayo Clinic as well as review of death certificates for patients who died. Patients were sent letters of inquiry if they had not visited Mayo Clinic in the preceding year. The risk of progression to MM and AL was compared to those expected on the basis of Surveillance, Epidemiology and End Results (SEER) rates for MM in Iowa and the prevalence of AL in Olmsted County, Minnesota. Two-hundred twenty-three patients fulfilled the criteria for Idiopathic Bence Jones Proteinuria during the 37-year period (1960 – 1996). The median age at diagnosis was 69 yrs (range, 36–90 yrs) and only 1% were < 40 years of age. Sixty-seven percent were male. The urine M protein ranged from unmeasurable to 4.7 g/24h. The median was 0.09 g/24h and only 8% were > 1 g/24h. Kappa light chain accounted for 57% while lambda was present in 43%. Eighty-one percent of patients died during follow-up. Twenty-six percent had a monoclonal light chain in the serum on immunofixation. Concentrations of uninvolved (normal, polyclonal or background) immunoglobulins were reduced in 45%. During 1408 person years of follow-up, 11 patients developed symptomatic MM (relative risk 28.5; 95% CI, 14.3 – 51.1) and an additional 9 patients developed AL (relative risk 61.8; 95% CI, 28.3 – 117.4). The cumulative probability of progression to active MM or AL was 7% at 5 yrs, 13.5% at 10 yrs., and 18% at 15 yrs. The factors evaluated with respect to predicting progression to MM or AL included sex, hemoglobin value, serum albumin, amount of urine M protein/24h, type of urine light chain (kappa or lambda), reduction of uninvolved (background) immunoglobulins, and elevation of serum calcium or creatinine. The amount of the urine M protein/24h was the only significantly predictive parameter for progression. As a continuous variable, a higher urine M protein was associated with an increased risk of progression (hazard ratio = 2.1 for a 1g increase, p=0.003). The amount of the urine M protein was also significant as a dichotomous variable. Patients who had a urine M protein ≥ 1g/24h had an increased risk of progression (hazard ratio = 3.6, p=0.007). We conclude that patients with Idiopathic Bence Jones Proteinuria are at risk for the development of MM or AL and need to be followed indefinitely.


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