ERCC1 expression is a predictor of survival in resected patients with non-small cell lung cancer

STUDY OBJECTIVES: Proteins of the nucleotide excision repair pathway repair DNA damage. The excision repair cross-complementing (ERCC) gene family reduces damage to DNA by nucleotide excision and repair. Impaired nuclear excision repair could lead to increased genomic instability that in turn could lead to a more malignant phenotypic behavior of tumors. We therefore evaluated the effect of intratumoral ERCC1 expression on survival in non-small cell lung cancer (NSCLC) patients who underwent surgical resection for cure. DESIGN: Resected tumor and the corresponding normal lung specimens from 51 patients with NSCLC who underwent surgical resection were immediately frozen in liquid nitrogen. Total RNA was extracted, reverse transcribed, and amplified with intron-spanning primers. Quantitation for ERCC1 was done using the Taqman procedure, and gene expression was normalized using 18SrRNA expression as internal reference with ERCC1 levels expressed a unit-less ratio. RESULTS: Tumoral ERCC1 expression ranged from 4.96 to 2,008, with a median value of 54.76. Using an ERCC1 value of 50 to dichotomize the cohort, there was a statistically significant difference in median survival for patients with ERCC1 expression > 50 (94.6 months) compared to < 50 (35.5 months) [p = 0.01]. Multivariate analysis revealed that high ERCC1 expression independently predicted for longer survival. There were no significant correlations between ERCC1 expression in tumor tissue and normal lung. CONCLUSIONS: We conclude that resected NSCLC patients with high ERCC1 expression (> 50) have a better survival when compared to patients with low ERCC1 expression (< 50). We postulate that an intact DNA repair mechanism may reduce the accumulation of genetic aberrations that are thought to contribute to a tumors malignant potential and therefore the risk of relapse after definitive treatment. Future adjuvant and neoadjuvant chemotherapy trials in NSCLC could stratify patients according to their ERCC1 expression levels.     

Serum endocan as a survival predictor for patients with liver cirrhosis

BACKGROUND:

The relationship between endocan expression and outcome in patients with chronic liver disease is not fully understood.

OBJECTIVE:

To examine whether serum endocan level is predictive of outcome in patients with liver cirrhosis.

METHODS:

A total of 68 patients with liver cirrhosis were enrolled. Outcome predictors were analyzed using the Cox proportional hazards model. The overall survival rates were calculated using the Kaplan-Meier method, and differences were evaluated using the log-rank test.

RESULTS:

During the median follow-up period (7.1 years), nine patients had hepatocellular carcinoma (HCC) and 10 patients died. Of the deceased patients, nine died due to hepatic decompensation or associated conditions. No significant factors were found to be predictive of the occurrence of HCC. In contrast, an elevated serum endocan level (≥2.0 ng/mL; HR 2.34 [95% CI 1.05 to 7.03]; P=0.037) and high Child-Pugh grade B/C (HR 2.65 [95% CI 1.30 to 6.89; P=0.006) were predictive of poor survival. Kaplan-Meier analysis revealed that the respective cumulative survival rates at five and 10 years were 97.1% and 87.4% in patients with serum endocan levels <2.0 ng/mL and 85.8% and 64.4% in patients with levels ≥2.0 ng/mL (P=0.009), respectively. Moreover, the cumulative survival rates were significantly different among the patient groups divided according to serum endocan level and Child-Pugh grade (P=0.002).

CONCLUSION:

These findings suggest that serum endocan level may be a survival predictor for patients with liver cirrhosis.     

MELD score as a predictor of pretransplant and posttransplant survival in OPTN/UNOS status 1 patients

The Model for End-Stage Liver Disease (MELD) score is predictive of survival and is used to prioritize patients with chronic liver disease patients for orthotopic liver transplantation (OLT). The aims of this study are (1) to assess the ability of MELD score at listing to predict pretransplant and posttransplant survival for nonchronic liver disease patients listed with the Organ Procurement and Transplantation Network/ United Network for Organ Sharing (OPTN/UNOS) as Status 1; and (2) to compare survival associated with 4 diagnostic groups within the Status 1 designation. The study population consisted of adult patients listed for OLT at Status 1 in the UNOS national database between November 1, 1999 and March 14, 2002 (N = 720). Events within 30 days of listing were analyzed using Kaplan-Meier and Cox regression methodology. Patients meeting criteria for fulminant hepatic failure without acetaminophen toxicity (FHF-NA, n = 312) had the poorest survival probability while awaiting OLT; this was negatively correlated with MELD score (P =.0001). These patients experienced the greatest survival benefit associated with OLT, with an estimated improvement of survival from about 58% to 91% (P <.0001). Patients listed for primary nonfunction within 7 days of OLT (n = 268) did not show mortality to be related to MELD score (P =.41) and did not show a significant association between survival and OLT (P =.68). In conclusion, liver allocation within the Status 1 designation may need to be further stratified by diagnosis, and MELD score may be useful for prioritizing FHF-NA candidates.     

Pleural fluid pH as a predictor of survival for patients with malignant pleural effusions

STUDY OBJECTIVES: To assess the accuracy of pleural fluid (PF) pH in predicting duration of survival of patients with malignant pleural effusions. DESIGN: Analysis of patient-level data from nine sources retrieved from a MEDLINE search and correspondence with primary investigators. STUDY SELECTION: Published and unpublished studies that report PF pH values and duration of survival of patients with malignant pleural effusions. DATA COLLECTION AND ANALYSIS: Primary investigators supplied patient-level data (n = 417), which was examined by receiver operating characteristic (ROC) analysis, logistic regression, and survival time modeling to determine the utility of PF pH for predicting survival compared with other clinical factors. The primary investigations were graded for study design. MEASUREMENTS AND RESULTS: Median survival (n = 417) was 4.0 months: PF pH (p < 0.0039) was an independent predictor of survival duration. A PF pH test threshold < or = 7.28 had the highest accuracy for identifying poor 1-, 2-, and 3-month survivals. The predictive accuracies of PF pH (area under the ROC curve range, 0.571 to 0.662) and a PF pH-high-risk tumor (lung, soft tissues, renal, ovary, gastrointestinal, prostate, and oropharynx) model (odds ratio range, 2.91 to 6.67), however, were modest for predicting 1-, 2-, and 3-month survival. Only 54.4% and 62.7% of patients identified by PF pH < or = 7.28 or the PF pH-high-risk tumor model to die within 3 months were correctly classified. Weaknesses of the primary data were identified. CONCLUSIONS: PF pH has insufficient predictive accuracy for selecting patients for pleurodesis on the basis of estimated survival.     

The ankle—brachial index as a predictor of survival in patients with peripheral vascular disease

Objective: To determine whether the ankle—brachial index (ABI) predicts survival rates among patients with peripheral vascular disease. Design: A retrospective survival analysis of patients with abnormal ABIs who visited the authors’ blood-flow laboratory during 1987. The National Death Index was used to ascertain survival status for all patients up to January 1, 1992. Kaplan-Meier and Cox proportional hazards analyses were used to determine the relationship between increasing lower-extremity ischemia, measured by ABI, and survival time. Clinical characteristics controlled for included age, smoking history, gender, and comorbidities, as well as the presence of lower-extremity rest pain, ulcer, or gangrene. Setting: A university hospital blood-flow laboratory. Patients/participants: Four hundred twenty-two patients who had no prior history of lower-extremity vascular procedures and who had ABIs < 0.92 in 1987. Results: Cumulative survival probabilities at 52 months’ (4.3 years’) follow-up were 69% for patients who had ABIs =0.5–0.91, 62% for patients who had ABIs =0.31–0.49, and 47% for patients who had ABIs ≤0.3. In multivariate Cox proportional hazard analysis, the relative hazard of death was 1.8 (95% confidence interval =1.2–2.9, p<0.01) for the patients who had ABIs ≤0.3 compared with the patients who had ABIs 0.5–0.91. Other independent predictors of poorer survival included age >65 years (p<0.001); a diagnosis of cancer, renal failure, or chronic lung disease (p<0.001); and congestive heart failure (p<0.04). Conclusion: The ABI is a powerful tool for predicting survival in patients with peripheral vascular disease. Patients with ABIs ≤ 0.3 have significantly poorer survival than do patients with ABIs 0.31–0.91. Further study is needed to determine whether aggressive coronary risk-factor modification, a work-up for undiagnosed coronary or cerebrovascular atherosclerotic disease, or aggressive therapy for known atherosclerosis can improve survival of patients with ABIs ≤ 0.3. Presented at the annual meeting of the Society of General Internal Medicine, April 27–29, 1994, Washington, DC. Supported in part by grant number 1R01HS07184-01A2 from the Agency for Health Care Policy and Research to Northwestern University Medical School.     

KISS1 methylation and expression as predictors of disease progression in colorectal cancer patients

AIM:To examine the effect of aberrant methylation of the KISS1 promoter on the development of colorectal cancer(CRC)and to investigate reversing aberrant methylation of the KISS1 promoter as a potential therapeutic target.METHODS:KISS1 promoter methylation,mRNA expression and protein expression were detected by methylation-specific polymerase chain reaction(PCR),real-time quantitative PCR and Western blotting,respectively,in 126 CRC tissues and 142 normal colorectal tissues.Human CRC cells with KISS1 promoter hypermethylation and poor KISS1 expression were treated in vitro with 5-aza-2’-deoxycytidine(5-Aza-CdR).After treatment,KISS1 promoter methylation,KISS1 mRNA and protein expression and cell migration and invasion were evaluated.RESULTS:Hypermethylation of KISS1 occurred frequently in CRC samples(83.1%,105/126),but was infrequent in normal colorectal tissues(6.34%,9/142).Moreover,KISS1 methylation was associated with tumor differentiation,the depth of invasion,lymph node metastasis and distant metastasis(P<0.001).KISS1methylation was also associated with low KISS1 expression(P<0.001).Furthermore,we observed re-expression of the KISS1 gene and decreased cell migration after 5-Aza-CdR treatment in a CRC cell line.CONCLUSION:These data suggest that KISS1 is down-regulated in cancer tissues via promoter hypermethylation and therefore may represent a candidate target for treating metastatic CRC.     

COX-2在卵巢上皮癌中的表达及其与黏蛋白MUC-1表达相关性的探讨

目的 探讨COX-2及MUC-1在卵巢上皮癌中的表达及临床意义。方法 采用SP免疫组织化学方法，对39例卵巢上皮癌、11例良性卵巢上皮瘤和10例正常卵巢组织的石蜡标本作COX-2及MUC-1的检测，并分析卵巢上皮癌的临床病理资料。结果 正常卵巢组织COX-2及MUC-1均呈阴性表达，良性卵巢上皮瘤COX-2呈阴性表达，MUC-1呈阳性表达。卵巢上皮癌中有COX-2及MUC-1表达，COX-2在正常卵巢，卵巢良性肿瘤与卵巢恶性肿瘤之间的表达有极显著差异（P〈0．01）；MUC-1在正常卵巢、卵巢良性与恶性肿瘤之间的表达有极显著差异（P〈0．01）；卵巢上皮癌与卵巢上皮瘤相比表达呈升高趋势，但无统计学意义（P〉0．05）；COX-2的阳性表达与卵巢上皮癌的临床分期、组织分化程度及病理类型无关（P〉0．05）；MUC-1的阳性表达与卵巢上皮癌的临床分期、组织分化程度及病理类型有关（P〈0，05）；COX-2及MUC-1的阳性表达与卵巢上皮癌的预后有关（P〈0．05）；（4）COX-2及MUC-l在卵巢上皮癌中的表达呈一致性相关，二者表达无显著性差异（P〉0．05），具有相关性（P=0．012）。结论 COX-2及MUC-1可能是卵巢上皮癌发生的相关基因，与肿瘤的发展及转移有关，检测COX-2及MUC-1可以估计卵巢上皮癌患者的预后，辅助指导临床化疗。     

High nuclear ABCG1 expression is a poor predictor for hepatocellular carcinoma patient survival

BackgroundATP-binding cassette transporter G1 (ABCG1) regulates cellular cholesterol homeostasis and plays a significant role in tumor immunity. But, for hepatocellular carcinoma (HCC), the role of ABCG1 has not been investigated. Thus, the aim of this study was to evaluate the prognostic value and clinicopathological significance of ABCG1 in HCC.MethodsOne hundred and four adult patients with HCC were enrolled, and ABCG1 expression in paired HCC specimens was determined by immunohistochemistry. All these patients were stratified by ABCG1 expression, Kaplan-Meier analysis was used to compare the overall survival (OS) and recurrence-free survival (RFS), and Cox regression analysis was used to determine independent predictors of tumor recurrence.ResultsUpregulation of ABCG1 was observed in HCC samples compared to matched tumor-adjacent tissues. Patients with high nuclear ABCG1 expression had lower OS and RFS (P = 0.012 and P = 0.020, respectively). High nuclear ABCG1 expression was related to larger tumor size (P = 0.004) and tumor recurrence (P = 0.027). Although ABCG1 was expressed in the cytoplasm, cytosolic expression could not predict the outcome in patients with HCC. A new stratification pattern was established based on the heterogenous ABCG1 expression pattern: high risk (High^nucleus/Low^cytosol), moderate risk (High^nucleus/High^cytosol or Low^nucleus/Low^cytosol), and low risk (Low^nucleus/High^cytosol). This ABCG1-based risk stratification could distinguish the different OS and RFS in patients with HCC. Multivariate Cox regression analysis indicated that ABCG1 high risk was an independent predictor of poor RFS (P = 0.015).ConclusionsHigh nuclear ABCG1 expression indicates poor prognosis in patients with HCC. Asymmetric distribution of ABCG1 in the nucleus and cytoplasm may have an important role in tumor recurrence.     

Semi-automated QRS score as a predictor of survival in CRT treated patients with strict left bundle branch block

Background

Cardiac Resynchronization Therapy (CRT) is widely used for treating selected heart failure patients, but patients with myocardial scar respond worse to treatment. The Selvester QRS scoring system estimates myocardial scar burden using 12-lead ECG. This study's objective was to investigate the scores correlation to mortality in a CRT population.

Osteopontin: a novel predictor of survival in patients with systemic light-chain amyloidosis

Abstract

Background: Troponin-T (cTnT) and NT-proBNP provide prognostic information in light-chain amyloidosis (AL). Thus, these biomarkers are widely used in clinical routine for risk stratification. Recently, plasma level of osteopontin (OPN), a secreted phosphoglycoprotein expressed by a variety of cell types, has been reported as a risk predictor in various cardiovascular diseases.

Methods: OPN was determined retrospectively in 150 consecutive patients newly diagnosed with AL amyloidosis. All patients were evaluated according to a routine protocol including electrocardiography, echocardiography and laboratory testing.

Results: Mean OPN was 591?±?37?ng/mL. Cardiac involvement was established in 83 (55.3%). Median OPN plasma level were associated with number of organs involved, renal function, eligibility for high-dose melphalan chemotherapy and autologous stem cell transplantation, and severity of cardiac amyloidosis. Median follow-up was 19.2 months. 1-year all-cause-survival was 83.4%. The cut-offs discriminating 1-year all-cause-mortality for NT-proBNP, troponin T, and OPN were 2544?ng/L, 0.035?µg/L, and 426.8?ng/mL, respectively. Outcome was worse in patients with biomarkers above the individual ROC derived cut-off. A significant improvement of survival was observed in patients with cTNT >0.035?µg/L or NT-proBNP >2544?ng/L and OPN below ROC-derived cut-off of 426.8?ng/mL as compared to patients with OPN above 426.8?ng/L. No further discrimination was achieved by OPN in the cohorts of low troponin T or low NT-proBNP, respectively. Separate multivariate models identified OPN (cut-off 426.8?ng/mL) and troponin T (cut-off 0.035?µg/L) as independent predictors of all-cause-mortality.

Conclusions: These data demonstrated that OPN appears to be a valuable marker in the clinical routine for evaluation of patients with AL amyloidosis, especially if it is used in combination with cTNT and/or NT-proBNP.     

HMGB1 as a predictor of infarct transmurality and functional recovery in patients with myocardial infarction

Abstract. Andrassy M, Volz HC, Riedle N, Gitsioudis G, Seidel C, Laohachewin D, Zankl AR, Kaya Z, Bierhaus A, Giannitsis E, Katus HA, Korosoglou G (University of Heidelberg, Heidelberg, Germany). HMGB1 as a predictor of infarct transmurality and functional recovery in patients with myocardial infarction. J Intern Med 2011; 270 : 245–253. Objectives. High‐mobility group box 1 (HMGB1) protein is an innate danger signal for the initiation of host defence and tissue repair. The aim of this study was to analyse serum HMGB1 concentration and its correlation with infarct transmurality and functional recovery in patients with ST‐elevation (STEMI) and non‐ST‐elevation myocardial infarction (NSTEMI). Design. We prospectively examined patients with first‐time STEMI (n = 46) or NSTEMI (n = 49), treated according to current guidelines. Contrast‐enhanced cardiac magnetic resonance imaging was performed 2–4 days after infarction for the estimation of infarct transmurality and was repeated after 6 months for the estimation of residual left ventricular function. HMGB1 was measured 2–4 days after infarction. Results. High‐mobility group box 1 concentration was related to infarct size and to residual ejection fraction in patients with STEMI (r² = 0.81 and r² = 0.40, respectively, P < 0.001 for both) and NSTEMI (r² = 0.74 and r² = 0.25, respectively, P < 0.001 for both). Receiver operating characteristic (ROC) curve‐derived cut‐off values of 6.2 and 5.9 ng mL^?1 for patients with STEMI and NSTEMI, respectively, were predictive of infarct transmurality greater than 75% (STEMI: area under the curve (AUC) = 0.93, standard error (SE) = 0.04, 95% confidence interval (CI) = 0.81–0.98; NSTEMI: AUC = 0.96, SE = 0.04, 95% CI = 0.86–0.99). HMGB1 cut‐off values of 7.2 and 6.4 ng mL^?1 for patients with STEMI and NSTEMI, respectively, were predictive of residual ejection fraction 6 months after myocardial infarction (MI) (STEMI: AUC = 0.81, SE = 0.07, 95% CI = 0.66–0.91; NSTEMI: AUC = 0.81, SE = 0.09, 95% CI = 0.68–0.91). Conclusion. High‐mobility group box 1 serum levels represent a highly valuable surrogate marker for infarct transmurality and for the prediction of residual left ventricular function after MI.     

A behavioral rating scale as a predictor for survival of demented nursing home patients

As part of a study towards determinants of survival in nursing home patients with dementia, the prognostic value of a behavioral rating scale for nursing home patients is assessed in an 8-year follow-up study. The 2-year survival rate for the entire cohort (n = 569) was 56%. Women (n = 459) had a 2-year survival rate of 62%, and men (n = 110) had a 2-year survival rate of 40%. Items indicating physical impairment, dependency and apathy had most prognostic value. Items measuring aggressive or depressive behavior, and cognitive impairment were less predictive. These results were confirmed in a multivariate proportional hazards analysis. A prognostic model with age, gender and five behavioral items (needs help when walking, occupied in useful activity, restless at night, utters physical complaints, and socializes with other patients) substantially differentiated in survival chances in patients with dementia. The model gives a predicted 2-year survival chance of less than 20% or more than 80% in 80 of the 569 patients. When adjusted for the variables in the model, previous residence had no prognostic value anymore. Possibilities for further work in this area of research are discussed.     

Plasma level of cardiotrophin-1 as a prognostic predictor in patients with chronic heart failure

BACKGROUND: Cardiotrophin-1 (CT-1) is a member of the interleukin (IL-6) family of cytokines and is increased in patients with chronic heart failure (CHF). AIMS: To evaluate the prognostic role of CT-1 in patients with CHF. METHODS AND RESULTS: We measured the plasma levels of CT-1, brain natriuretic peptide (BNP), and IL-6 in 125 patients with CHF. Patients were monitored for a mean follow-up period of 2.9 years. Plasma levels of CT-1 increased with severity of CHF. There was a significant negative correlation between plasma CT-1 and left ventricular ejection fraction. There was a significant correlation between plasma CT-1 and log IL-6. During the follow-up period, 37 patients died. High plasma levels of CT-1, BNP, and IL-6 were independent predictors of mortality on stepwise multivariate analysis. The hazard ratio for mortality in patients with plasma BNP>170 pg/mL and CT-1>658 fmol/mL was 2.48 (95% confidence interval, 1.217-5.060) compared to those with plasma BNP>170 pg/mL and CT-1<658 fmol/mL (p=0.0124). CONCLUSION: These findings indicate that plasma CT-1 measurement provides additional prognostic information and that combined levels of CT-1 and BNP are more accurate at predicting mortality in patients with CHF than either marker alone.     

Early-stage serum Stanniocalcin 1 as a predictor of outcome in patients with aneurysmal subarachnoid hemorrhage

Stanniocalcin-1 (STC1) takes part in anti-inflammatory and anti-oxidative processes, thus demonstrating neuroprotective properties. Early brain injuries associated with initial subarachnoid hemorrhage typically led to secondary cerebral infarction and poor outcomes. This retrospective study aimed to clarify the clinical significance of serum STC1 level in patients with subarachnoid hemorrhage.We collected demographic information, comorbidities, neurological status in detail. All blood samples were collected on admission. Enzyme-linked immunosorbent assay kits were used to detect the serum level of STC1. Spearman analysis was used to explore the relationship between STC1 and clinical severity. Multivariate logistic regression was used to investigate the prognostic role of STC1 in patients with aneurysmal subarachnoid hemorrhage (aSAH). Receiver operating characteristic curve was performed to investigate the power of STC1 in predicting outcome in aSAH patients.Serum STC1 concentration was significantly higher in aSAH patients than in healthy individuals. Serum concentration of STC1 positively correlated with Hunt-Hess grade (r = 0.62, P < .01) and Fisher grade (r = 0.48, P < .01), and negatively correlated with Glasgow Coma Scale on admission (r = −0.45, P < .01). Patients with delayed cerebral ischemia (DCI) had higher level of serum STC1 than those without DCI (13.12 ± 1.44 vs 8.56 ± 0.31, P < .01). Moreover, patients with poor outcome had higher concentration of STC1 than patients with good outcome (11.82 ± 0.62 vs 8.21 ± 0.35,P < 0.01). Results of univariate and multivariate logistic analysis revealed that Hunt-hess III–IV, DCI, and high STC1 level were independent risk factors associated with poor outcome of patients with aSAH. Further analysis revealed that combination of STC1 with Hunt-hess grade was more superior to 2 indicators alone in predicting clinical outcome of aSAH patients.STC1 can be used as a novel biomarker in predicting outcome of patients with aSAH, especially when combined with Hunt-hess grade.     

Patient satisfaction with quality of life as a predictor of survival in pancreatic cancer

BACKGROUND: The goal of this study was to evaluate the association between patient satisfaction with quality of life (QoL) and survival in pancreatic cancer patients undergoing care in a community hospital comprehensive cancer center. PATIENTS AND METHODS: A consecutive case series of 55 cases of histologically confirmed pancreatic cancer treated at Cancer Treatment Centers of America at Midwestern Regional Medical Center was studied between 04/01 and 11/04. The Quality of Life Index (QLI) was utilized to assess patient satisfaction with QoL. QLI measures global QoL as well as the QoL in four major subscales: health and physical, social and economic, psychological and spiritual, and family. All scores range from 0 to 30 with higher scores indicating a better QoL. The Kaplan-Meier method was used to calculate survival. Log-rank test was used to study the equality of survival distributions. Multivariate Cox regression analyses were then performed to evaluate the joint prognostic significance of those QoL and clinical factors that were shown to be prognostic in univariate analyses. RESULTS: Of the 55 patients, 28 were newly diagnosed and 27 had prior treatment history. The median age was 55 yr (range 33-74 yr). Amajority (34) had stage IV disease at diagnosis. Health and physical subscale, family subscale, and global QoL were significantly associated with survival upon univariate analysis. Health and physical subscale was marginally significant upon multivariate analysis after controlling for the effects of stage at diagnosis. CONCLUSIONS: We found that baseline patient satisfaction with QoL, as measured by the QLI, provides useful prognostic information in patients with pancreatic cancer. While these findings require further investigation in large patient cohorts, they may have important implications for patient stratification in clinical trials, as well as aid in clinical decision-making.     

Peripheral blood monoclonal plasma cells as a predictor of survival in patients with multiple myeloma [see comments]

The purpose of this study was to quantitate the number and labeling index of monoclonal plasma cells in the blood of patients with newly diagnosed multiple myeloma (MM) to learn if these values were independent prognostic factors for survival. Patients were candidates for this study if they had untreated myeloma requiring therapy, were evaluated at our institution between 1984 and 1993, and had a sample of blood analyzed with a sensitive immunofluorescence technique for monoclonal plasma cells and the blood B-cell labelling index (BLI). The % blood monoclonal plasma cells (%BPC) and the BLI were analyzed along with stage, marrow plasma cell LI, % marrow plasma cells, calcium, creatinine, albumin, beta-2-microglobulin, and C-reactive protein as univariate and multivariate factors for survival. Eighty percent of the 254 patients accrued to this study had monoclonal BPC detected. The median % BPC was 6% and 57% (144 of 254) of patients had a high number (> or = 4%). Patients with > or = 4% BPC had a median survival of 2.4 years vs 4.4 years for those with < 4% BPC (P < .001). The BLI was also prognostic (P = .008). In a multivariate analysis, the % BPC, age, albumin, stage, marrow plasma cell LI, and the BLI were independent factors for survival. The %BPC and the marrow plasma cell LI best separated the group into low, intermediate, and high risk myeloma with median survivals of 52, 35, and 26 months, respectively. Patients with high %BPC were less likely to have lytic bone disease from their MM (P = .002). The %BPC and the BLI are independent prognostic factors for survival and are useful in identifying patients as low, intermediate, and high risk. Clonal cells in the blood should be quantified in future clinical trials for myeloma.