1q21 Gain Combined with High‐Risk Factors Is a Heterogeneous Prognostic Factor in Newly Diagnosed Multiple Myeloma: A Multicenter Study in China

Background and Objective: Multiple myeloma (MM) is characterized with significant cytogenetic changes and complex tumor microenvironment, thus patient survival is extremely heterogeneous. Various disease-related or patient-related factors affect the prognosis of patients. This study tried to analyze the prognostic indicators of patients with newly-treated MM, especially explored the prognosis of multiple cytogenetic abnormalities and the ratio of lymphocytes to monocytes (LMR). Additionally, we established a comprehensive prognostic model to help determine the patient prognosis. Methods: After screening, 603 patients of untreated MM from January 2008 to June 2017, with complete baseline indicators were enrolled into the study. By univariate and multivariate Cox analysis, risk factors related to the prognosis of patients were evaluated, and a weighted prognosis model was established to compare the survival differences of patients in each risk stratification. Result: Optimal thresholds of ALC, LWR, NLR and LMR were determined by ROC curve and Youdex index: ALC = 1.415, LWR = 0.325, NLR = 1.935, LMR = 2.95. Survival analysis showed that patients with LMR ≤ 2.95, ALC ≥ 1.415 and LWR ≥ 0.325 had significantly better survival compared with their respective control groups. Cox multivariate analysis showed that among the four indicators, only LMR≤2.95 was an independent adverse prognostic factor for overall survival (OS)(Figure 1A). 17p deletion, 1q21 amplification, t (4; 14) / t (14; 16) were define as high-risk cytogenetic abnormalities (HRA). Of the 603 patients, about 60% were associated with at least one high-risk cytogenetic event. Among them, the occurrence of cumulative 0, 1, 2, and 3 HRA were 39.6% (239/603), 42.5% (256/603), 16.6% (100/603), and 1.3% (8/603), respectively. There was no significant difference in survival among patients with same number of HRAs. The median OS of patients with 0, 1 and ≥ 2 HRA were not reached, 62.1 months (95% CI, 49.3-74.9) and 30.4 months (95% CI, 24.5-36.3), respectively (p <0.001)(Figure 1B).Final Cox regression model showed that age 65 ~ 74 (HR=1.77, 95%CI, 1.24-2.51, p=0.001), age ≥75 (HR=2.46, 95%CI, 1.69-3.58, p < 0.001), LDH≥247 U/L (HR =1.65, 95%CI, 1.07-2.51, p=0.023), ISS stage III (HR=1.76, 95%CI, 1.24-2.50, p=0.002), LMR≤2.95 (HR=1.53, 95%CI, 1.08-2.18, p=0.017), 1 HRA (HR=1.87, 95%CI, 1.27-2.75, p=0.002) and ≥2 HRA (HR=3.48, 95%CI, 2.22-5.45, p<0.001) are independent adverse prognostic factors for OS. Then weighted risk factors were summed to establish a comprehensive prognosis model, with a total score range of 0-6 points. Accordingly, the whole cohort was divided into low risk (0-1 points, 45.4%), intermediate risk (2 points, 27.9%), high risk (3 points, 19.2%) and ultra-high risk (4-6 points, 7.5 %) groups. The median OS of the four risk groups were 85.8 months (67.1-104.5), 49.0 months (44.7-53.3), 35.4 months (31.3-39.5), and 23.2 months (18.8-27.6), respectively (p<0.001). The C-statistics of this prognostic model is 0.68 (95% CI, 0.64-0.71), which is significantly better than the D-S stage (C-statistics = 0.52, 95% CI, 0.50-0.55, p <0.001), ISS (C-statistics = 0.60, 95% CI, 0.57-0.64, p <0.001) and R-ISS stage (C-statistics = 0.60, 95% CI, 0.57-0.63, p <0.001). Bootstrap resampling and calibration curve showed that the model has an accurate predictive effect on both short-term and long-term prognosis of patients(Figure 1C). Conclusion: In our analysis, ALC, LWR, LMR were associated with poor prognosis in NDMM patients, while NLR had no significant prognostic significance. Among the four indicators, LMR≤2.95 was the only independent prognostic factor. In NDMM patients, survival of patients with the same number of high-risk cytogenetic abnormalities were comparable with each other, regardless of whichever combination of HRA. Higher number of high-risk cytogenetic abnormalities were associated with worse prognosis. Cox multivariate analysis showed that, old age (65-74 years old, ≥75 years old), increased LDH (≥247 U/L), decreased LMR (≤2.95), ISS III, 1 HRA and ≥ 2 HRA were independent adverse prognostic factors that affect the OS of MM patients. 4. A comprehensive weighted prognostic model was established with the above factors, which was proved to effectively distinguish different prognosis of patients. Figure 1 Disclosures No relevant conflicts of interest to declare.

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Early Infection Risk in Newly Diagnosed Multiple Myeloma Patients in the Modern Era

Blood ◽

10.1182/blood-2021-146035 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3794-3794

Author(s):

Ryan Stevenson ◽

Diane M. Carpenter ◽

Adnan Khan ◽

Raleigh Fatoki ◽

Sumanth Rajagopal ◽

...

Keyword(s):

Risk Factors ◽

Multiple Myeloma ◽

High Risk ◽

Race And Ethnicity ◽

The United States ◽

Newly Diagnosed ◽

Infection Rates ◽

Community Based ◽

The Past ◽

Standard Risk

Abstract Background: Multiple myeloma (MM) is the second most common hematologic malignancy, with an estimated 30,000 new cases in the United States annually. Advances in management of MM over the past 20 years have significantly improved outcomes, but MM continues to be an incurable disease. Infections continue to be a major cause of morbidity and mortality, with a high proportion of MM patient developing infections within the first 3 months of diagnosis. There have been limited data on infection rates in MM patients in community-based oncology setting over the past two decades. This study looked to define infection rates and associated risk factors in newly diagnosed MM patients within 90 days of initial diagnosis. Methods: A retrospective, observational study was conducted on MM patients ages 18-89 newly diagnosed January 1, 2010-December 31, 2018 within Kaiser Permanente Northern California. Patients were required to have a minimum of one year of membership prior to MM diagnosis. SEER data was used to identify MM patients, and clinical data were extracted from the electronic health record. Bacterial, viral, and fungal infections were identified using ICD9/ICD10 codes. Baseline demographic and clinical characteristics from visit notes, laboratory and pathology results, and transplant data from utilization and claims data were analyzed to assess infection risks. High-risk cytogenetics was defined as notation of the following in pathology reports or oncology notes: add 1q, t(4:14), t(14:16), t(14:20), deletion of 17p. Bivariate analyses were conducted to assess differences across groups using the chi-squared test and the Wilcoxon-Mann-Whitney nonparametric test. Results: A total of 2030 newly diagnosed MM patients identified for this study. Median age at diagnosis was and n=828 (40.8%) of patients were female. Among this cohort, 522 (25.7%) had an infection within 90 days of MM diagnosis. The median age of patients having infections was 71 years (IQR 63-80), and the median age of those not having infections was 68 years (IQR 60-76, p<0.001). The median Charlson Comorbidity Index (CCI) of patients having infections was 3 (IQR 1-5) and the median CCI of those not having infections was 2 (IQR 1-4, p<0.001). Patients having hemoglobin <10.0 g/dl were more likely to have infection than those having hemoglobin >10.0 g/dl (30.4% vs. 23.6% respectively, p=0.011). Similarly, patients presenting with hypercalcemia (calcium >11.0 mg/dL) were more likely to have infection (37.4% vs. 24.6% in patients having calcium <11.0 mg/dL, p<0.001) as were patients with creatinine clearance <60.0 mL/min of those having <60.0 mL/min vs. 20.7% of those having >60.0 mL/min, p<0.001). Patients having indicators of high-risk cytogenetics were less likely to have infections within 90 days of diagnosis compared to those with standard risk cytogenetics (21.1% vs 26.2% respectively, p=0.031). We did not detect significant differences across transplant eligible status within the first year after diagnosis (22.1% infection among transplant eligible vs. 26.6% among those who were not transplant eligible, p=0.059) nor across sex (27.3% among females vs. 24.6% among males, p=0.176). Additionally, no significant differences in infection were detected across race and ethnicity (24.0% infection among Asian patients, 26.4% among Black patients, 27.7% among Hispanic patients, 25.5% among White patients, and 14.3% among patients having unknown or other race and ethnicity, p=0.741). Conclusions: In this community-based oncology study, infection within 90 days of diagnosis continues to be a significant complication of multiple myeloma and these results are comparable to previous studies. Risk factors for infection include age, CCI, standard risk cytogenetics, anemia, hypercalcemia, and renal failure. Stem cell transplant, sex and ethnicity were not associated with increased risk for infection. Future analysis will include assessments of hospitalization and mortality associated with infection. This study illustrates the importance of further research looking at decreasing infection rates in multiple myeloma patients. Disclosures No relevant conflicts of interest to declare.

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Prognostic role of circulating exosomal miRNAs in multiple myeloma

Blood ◽

10.1182/blood-2016-09-742296 ◽

2017 ◽

Vol 129 (17) ◽

pp. 2429-2436 ◽

Cited By ~ 92

Author(s):

Salomon Manier ◽

Chia-Jen Liu ◽

Hervé Avet-Loiseau ◽

Jihye Park ◽

Jiantao Shi ◽

...

Keyword(s):

Risk Factors ◽

Multiple Myeloma ◽

High Risk ◽

Survival Prediction ◽

Prognostic Role ◽

High Risk Factors ◽

Key Points ◽

Exosomal Mirnas

Key Points Two circulating exosomal microRNAs, let-7b and miR-18a, improved survival prediction in patients with MM. Circulating exosomal miRNAs enhanced the stratification of patients with high-risk factors.

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Preoperative controlling nutritional status (CONUT) score is a prognostic factor for early-stage cervical cancer patients with high-risk factors

Gynecologic Oncology ◽

10.1016/j.ygyno.2021.06.012 ◽

2021 ◽

Author(s):

Guangyu Zhang ◽

Youzhong Zhang ◽

Fangfang He ◽

Haijian Wu ◽

Cong Wang ◽

...

Keyword(s):

Risk Factors ◽

Cervical Cancer ◽

High Risk ◽

Prognostic Factor ◽

Nutritional Status ◽

Cancer Patients ◽

Early Stage ◽

High Risk Factors ◽

Early Stage Cervical Cancer ◽

Conut Score

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Abnormal Metaphase Cytogenetics Adds to Currently Known Risk-Factors for Venous Thromboembolism in Multiple Myeloma: Derivation of the PRISM score

Blood ◽

10.1182/blood-2020-137525 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 29-30

Author(s):

Rajshekhar Chakraborty ◽

Lisa Rybicki ◽

Jason Valent ◽

Alex V. Mejia Garcia ◽

Beth M. Faiman ◽

...

Keyword(s):

Risk Factors ◽

Multiple Myeloma ◽

High Risk ◽

Research Funding ◽

Treatment Initiation ◽

Newly Diagnosed ◽

Prism Score ◽

C Statistic ◽

The Impact ◽

Disease Specific

Background: Prevention and management of venous thromboembolic events [VTE] is an important component of supportive care in newly diagnosed multiple myeloma [MM], especially in the era of immunomodulatory drugs [IMiDs]. Recently, two validated risk assessment models [RAMs], SAVED and IMPEDE-VTE, were developed to identify patients at high risk of VTE. However, these models have following limitations: (1) Patients were not uniformly treated in the era of contemporary MM therapy (2) Disease-specific variables were not available in the databases from which these scores were derived. Our primary aim was to develop a simple predictive model for VTE in MM using patient-specific, disease-specific, and treatment-specific variables. Our secondary aim was to assess the impact of VTE on overall survival [OS]. Methods: All consecutive patients with newly diagnosed MM treated at Cleveland Clinic from 1/1/2008 to 12/31/2018 were included in our analysis. The primary objective was to identify baseline variables associated with VTE within 12 months of treatment initiation. Candidate variables included those in IMWG, SAVED, and IMPEDE-VTE models as well as additional risk-factors from literature review in MM and cancer-associated VTE. Stepwise selection with variable entry criterion of p<0.20 and a variable retention criterion of p<0.05 was used to identify significant factors on multivariable analysis [MVA]. RAM was developed by subtracting 1 from the hazard ratio of a potential variable, rounding to the nearest 0.5, and multiplying by 2 to obtain a whole number. The impact of VTE on OS was assessed with landmark analysis. Results: A total of 934 patients with newly diagnosed MM and available data on VTE occurrence were considered for inclusion. We excluded patients with VTE within 6 months before starting therapy [n=5] and patients on therapeutic anticoagulation or receiving >1 prophylactic regimen [n=146], resulting in a total of 783 patients for model development. The most common induction regimen was bortezomib [V]-lenalidomide [R]-dexamethasone [VRD; 41%], followed by VD [22%], RD [20%], V-cyclophosphamide-dexamethasone [VCD; 11%], and others [7%]. Median age at treatment initiation was 63 years [range, 22-91], 55% were males, and 20% were Blacks. ISS stage III disease was present in 32%, high-risk FISH in 23%, abnormal metaphase cytogenetics in 18%, and serum creatinine >2 mg/dl in 19% of patients. Notably, 76% had received a dexamethasone dose of 120-160 mg/cycle, with only 5.9% started on a higher dose [>160 mg/cycle]. The most common thromboprophylaxis agent was aspirin [60%], followed by low molecular weight heparin [LMWH; 3.8%]; 37% of patients received no thromboprophylaxis. Erythropoietin and intravenous immunoglobulin were used in 2.9% and 1.2% of patients respectively. Median time to VTE from treatment initiation was 3.2 months. Cumulative incidence of VTE at 6 and 12 months was 8.2% [95% CI, 6.6-10.1] and 11.5% [95% CI, 9.5-13.6] respectively. Factors significantly associated with development of VTE on MVA were combined to develop the PRISM score [Table 1]: Prior VTE history [HR 5.06; 8 points], Black Race [HR 1.71; 1 point], IMiD use [HR 2.17; 2 points], Surgery within 3 months [HR 3.44; 5 points], and abnormal Metaphase cytogenetics [HR 2.10; 2 points]. The theoretical score range is 0-18, with a HR of 1.28 per 1-point increase in score [c-statistic 0.62]. Internal bootstrap validation including 1,000 samples showed a c-statistic of 0.62 [IQR, 0.60-0.64]. Using three risk groups by recursive partitioning analysis, 17.8%, 74%, and 8.1% belonged to low [0], intermediate [1-6], and high-risk [>6] groups respectively. The 12-month cumulative incidence of VTE in the 3 respective groups were 2.7%, 10.8%, and 36.5% [Figure 1]. Occurrence of VTE in the first 12 months was not associated with worse OS on landmark analysis at 3, 6, 9, and 12 months. Conclusion: We have developed and internally validated a RAM for VTE in MM in the context of contemporary MM therapy including disease-specific variables. Studies of external validation and comparison with existing RAMs are warranted. The PRISM Score could be used to identify high-risk patients for thromboprophylaxis. Figure Disclosures Valent: Amgen Inc.: Other: Teaching, Speakers Bureau; Takeda Pharmaceuticals: Other: Teaching, Speakers Bureau; Celgene: Other: Teaching, Speakers Bureau. Khouri:Sanofi Genzyme: Other: Advisory Board. Anwer:Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau. Khorana:Pharmacyclics: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria; Medscape: Honoraria; Leo Pharma: Honoraria; Seattle Genetics: Honoraria; Pharmacyte: Honoraria; Leap: Research Funding; Bayer: Honoraria; Janssen: Honoraria; Merck: Research Funding; Array: Other: Research funding (to institution); BMS: Honoraria, Research Funding.

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Serum Free Light Chain Ratio (FLCr) Is a Powerful Prognostic Factor For Survival In Newly Diagnosed Multiple Myeloma (MM) Eligible For High Dose Melphalan (HDM)

Blood ◽

10.1182/blood.v122.21.1873.1873 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1873-1873

Author(s):

Graça Esteves ◽

Manuel L Neves ◽

Helena Martins ◽

Carlos M. Martins ◽

Maria Joao Costa ◽

...

Keyword(s):

Risk Factors ◽

Multiple Myeloma ◽

Prognostic Factor ◽

Light Chain ◽

Prognostic Value ◽

Stage Ii ◽

Newly Diagnosed ◽

Baseline Serum ◽

Significant Difference

Abstract Introduction MM is a B cell malignancy characterized by the presence of a monoclonal immunoglobulin (Ig) in the serum and/or urine produced by clonal plasma cells. MM has a variable outcome depending on age, stage and cytogenetic abnormalities. FLCr is a readily available laboratory test and has independent prognostic significance in all the plasma cell disease entities, helping to clarify International Staging System (ISS), namely the heterogeneous stage II. In the era of new therapeutic agents trending to personalized therapy, its prognostic value needs to be proved. Purpose To evaluate the prognostic value of baseline serum FLCr on outcome of patients with newly diagnosed MM eligible for HDM treated with thalidomide or bortezomib based regimens. Methods This is a retrospective study, from January 2005 to December 2012. We analyzed the relationship of baseline FLCr with outcome and its contribution to clarify the prognostic value of ISS. Serum FLC levels were measured in frozen sera drew at diagnosis before treatment, using a latex-enhanced immunoassay (The Binding Site, Birmingham, UK) on a Beckman Coulter nephelometric analyzer. FLCr was calculated as k/λ (reference range: 0,26-1,65). Abnormal FLCr was defined of <0,03 or >32,00 and standard FLCr of 0,03-32. Patients have been staged by ISS and Mayo Clinic stratification. All patients received at least two cycles of a bortezomib based regimen (64,7%), with doxorubicin and dexamethasone (PAD) in 55 patients (53,9%), with cyclophosphamide and dexamethasone (Cy-Bor-D) in 11 patients (10,8%) or thalidomide, doxorubicin and dexamethasone (TAD) in 36 patients (35,3%). Median follow-up from diagnosis was 30 months. Follow-up was through the review of each patient’s complete medical records at our center. Statistical analysis was performed with SPSS 20 ®. Results We reviewed 102 patients treated with thalidomide or bortezomib based-regimens eligible for HDM. Fifty one percent of patients were male and median age was 52 years (22-70y). The Ig type was IgG in 62,7%, IgA in 14,7%, IgD in 3,9%, light chains MM in 17,7% and non-secretory MM in 1,0% of patients. The median Hb level was 9,8 g/dL (5,3-16,7mg/L) and median serum albumin was 31,5 g/L (22,3-48,3g/L). Creatinine clearance <30ml/mn occurred in 18,6% of patients, 34,3% had elevated LDH and median β2-microglobulin was 6,61 mg/L (1,06-45,77mg/L). According to ISS, 39,2%% of patients were on stage I, 25,5%% on stage II and 35,3% on stage III. Clonal k light chain present in 58,8% of patients: 64,7% had abnormal FLCr (<0,03 or >32,00). Cytogenetic FISH analysis was performed in 86,3% of patients: 32,4% presented high-risk features. We observed a significant difference on overall survival (OS) and progression free survival (PFS) according to Mayo Clinic risk-factors: 0, not reached (NR), 1, NR, 2, 49 months and 3, 71 months for OS (P=0,000) and 0, 68 months, 1, 55 months, 2, 16 months and 3, 24 months for PFS (P=0,000). According the FLCr there was a significant advantage on OS for standard FLCr: NR vs 71 months (P=0,035). A trend to a better OS (P=0,061) was observed in stage II patients with standard FLCr but no significant difference at any stage. Conclusions Baseline serum FLCr associated to others risk-factors like serum β2-microglobuline and albumin is a powerful prognostic factor for survival in newly diagnosed MM eligible for HDM treated with thalidomide or bortezomib-based therapies. We fail to fully demonstrate FLCr prognostic value on ISS stage II patients, only a trend for better outcome with standard FLCr. Disclosures: Esteves: Janssen-Cylag and Celgene. Consultancy on the area of multiple myeloma and acute myeloid leukaemia: Consultancy. Raposo:Roche; lymphoproliferative diseases: Consultancy. Guerra:Novartis, Bristol-Myers Squibb and Amgen. Advisory bord meetings. Areas involved: Myeloproliferative neoplasms and acute leukaemia: Consultancy.

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Safety and Efficacy Outcomes with Lenalidomide Plus Dexamethasone in Relapsed or Refractory Multiple Myeloma Were Not Significantly Different for the Treatment of Patients with or without High-Risk Disease or Elderly Status

Blood ◽

10.1182/blood.v112.11.3701.3701 ◽

2008 ◽

Vol 112 (11) ◽

pp. 3701-3701 ◽

Cited By ~ 3

Author(s):

Asher Chanan-Khan ◽

Meletios A Dimopoulos ◽

Donna M. Weber ◽

Andrew Spencer ◽

Michel Attal ◽

...

Keyword(s):

Risk Factors ◽

Multiple Myeloma ◽

High Risk ◽

Adverse Events ◽

Disease Stage ◽

Safety And Efficacy ◽

Β2 Microglobulin ◽

High Risk Factors ◽

High Risk Disease ◽

Grade 3

Abstract Introduction: Lenalidomide is effective in the treatment of multiple myeloma (MM). The MM-009 and MM-010 randomized, double-blind, placebo-controlled phase III trials showed that lenalidomide in combination with dexamethasone induced significantly higher overall response (OR), and longer median time-to-progression (TTP) than dexamethasone alone in patients with relapsed or refractory MM (Weber et al, NEJM 2007; Dimopoulos et al, NEJM 2007). Previously identified predictors of high-risk disease and poor prognosis in MM include age (≥ 65 vs. < 65 years), Eastern Cooperative Oncology Group (ECOG) performance status (ECOG score ≥ 1 vs. 0), IgA status (IgA MM vs. non-IgA MM), disease stage (Durie-Salmon stage III vs. I–II), and β2-microglobulin level (> 2.5 mg/L vs. ≤ 2.5 mg/L). Here, we compared safety and efficacy outcomes of lenalidomide plus dexamethasone in patients with or without these high-risk factors. Methods: Patients with or without high-risk factors, pooled from MM-009 and MM-010, were randomized to receive lenalidomide (25 mg/day on days 1–21 of each 28-day cycle) plus dexamethasone (40 mg/day on days 1–4, 9–12, and 17–20 of each 28-day cycle for 4 cycles, with 40 mg/day on days 1–4 only from cycle 5 onwards). OR and TTP were based on data obtained before unblinding (June 2005 [MM-009] and August 2005 [MM-010]). Results: OR rate and median TTP were comparable between low- and high-risk patients based on age, ECOG score, IgA status, and Durie-Salmon disease stage. Patients with β2-microglobulin ≤ 2.5 mg/L had significantly better OR and TTP than those with β2-microglobulin >2.5 mg/L (Table). Grade 3 or 4 adverse events for the different subgroups were similar to those observed for the overall study population. Most grade 3 or 4 adverse events were similar between high-risk and low-risk groups. Significant differences in grade 3 or 4 adverse events were neutropenia for patients with Durie-Salmon stage III vs. I–II (40% vs. 28%, p=0.03), thrombocytopenia for ≥ 65 years vs. < 65 years (17% vs. 9%, p=0.03) and those with β2-microglobulin ≤ 2.5 mg/L vs. >2.5 mg/L (16% vs. 7%, p=0.03), and anemia for those with β2-microglobulin ≤ 2.5 mg/L vs. >2.5 mg/L (15% vs. 1%, p=0.0001). Grade 3 or 4 peripheral neuropathy was uncommon (≤2%) for all subgroups and not significantly different between those with high- and those with low-risk features. Conclusion: High OR rates, long TTP and manageable adverse events were observed with lenalidomide plus dexamethasone for patients with high-risk features. Advanced age, high ECOG score, presence of IgA, and advanced Durie-Salmon stage did not affect efficacy outcomes. Patients with high β2-microglobulin levels did have lower efficacy and more adverse events. Risk group OR rate, % P Median, TTP months P < 65 years (n=192) 61 0.73 11.1 0.91 ≥ 65 years (n=161) 60 13.2 ECOG 0 (n=152) 59 0.52 10.2 0.30 ECOG ≥ 1 (n=192) 62 13.1 Non-IgA (n=72) 57 0.10 11.2 0.65 IgA (n=267) 68 10.2 Durie-Salmon I–II (n=123) 61 0.89 13.6 0.21 Durie-Salmon III (n=229) 60 10.6 β2-microglobulin ≤ 2.5 mg/L (n=103) 73 0.002 15.2 0.004 β2-microglobulin > 2.5 mg/L (n=250) 56 9.5

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