The prognosis of clinical monoclonal B cell lymphocytosis differs from prognosis of Rai 0 chronic lymphocytic leukaemia and is recapitulated by biological risk factors According to the recent International Workshop on Chronic Lymphocytic Leukaemia (IWCLL) guidelines, diagnosis of chronic lymphocytic leukaemia (CLL) requires over 5AE0 · 10 9 /l circulating B-cells in the peripheral blood (Hallek et al, 2008). Based on IWCLL guidelines, asymptomatic monoclonal B-cells expansions characterized by a CLL-phenotype, but with less than 5AE0 · 10 9 /l circulating cells, enter the category of monoclonal B-cell lymphocytosis (MBL) (Marti et al, 2005;Hallek et al, 2008). The definition of MBL was initially prompted by the need to classify monoclonal B-cell expansions occasionally found in individuals from the general population whose probability to progress to symptomatic CLL would be uncertain (Rawstron et al, 2002a;Hoffbrand & Hamblin, 2007).MBL has been found in 3-7% of adults, in 9% of elderly individuals, and in over 10% of individuals with more than two first-degree relatives affected by CLL (Rawstron et al, 2002a,b;Marti et al, 2003;Ghia et al, 2004;Rachel et al, 2007;Shim et al, 2007;Dagklis et al, 2009). A fraction of MBL cases are diagnosed during the characterization of an otherwise asymptomatic lymphocytosis. Such cases represent clinical MBL (cMBL), and may be distinguished from low count MBL, that, in contrast, is accidentally found by screening individuals with a completely normal blood cell count (Dagklis et al, 2009).Based on published series, over 15% cMBL patients develop progressive CLL, 7% eventually require chemotherapy, and 2% cMBL had better humoral immune capacity and lower infection risk, lower prevalence of del11q22-q23/del17p13 and TP53 mutations, slower lymphocyte doubling time, and longer treatment-free survival. Also, cMBL diagnosis was a protective factor for treatment risk. Despite these favourable features, all cMBL were projected to progress, and lymphocytes <1AE2 · 10 9 /l and >3AE7 · 10 9 /l were the best thresholds predicting the lowest and highest risk of progression to CLL. Although IGHV status, CD38 and CD49d expression, and fluorescence in situ hybridization (FISH) karyotype individually predicted treatment-free survival, multivariate analysis identified the presence of +12 or del17p13 as the sole independent predictor of treatment requirement in cMBL (Hazard ratio: 5AE39, 95% confidence interval 1AE98-14AE44, P = 0AE001). Overall, these data showed that cMBL has a more favourable clinical course than Rai 0 CLL. Given that the biological profile can predict treatment requirement, stratification based on biological prognosticators may be helpful for cMBL management.

BACKGROUND: Although serum beta-2 microglobulin (B2M) represents a key variable for symptomatic multiple myeloma (MM) prognostication, its role in predicting the risk of progression of asymptomatic MM to symptomatic disease has not been explored. METHODS: This study was bases on a consecutive series of 148 patients with asymptomatic MM and explored the cumulative probability of progression to symptomatic MM as the primary endpoint. RESULTS: In univariate analysis, a serum B2M level >2.5 mg/L was associated with an increased probability of disease progression (5-year risk, 64.5%; P < .001) along with serum monoclonal component (sMC) (P < .001), urinary monoclonal component (uMC) (P < .001), and bone marrow plasma cells (BMPCs) (P < .001). In multivariate analysis, serum B2M was selected as an independent predictor of progression (hazard ratio, 3.30; P ¼.002). Serum B2M was combined with sMC, uMC, and BMPC to create a risk-stratification model based on 4 groups with different risk of progression: very low (5-year risk, 0%), low-intermediate (5-year risk, 19.6%), high-intermediate (5-year risk, 60.7%), and high (5-year risk, 80.7%). The model that included serum B2M along with sMC, uMC, and BMPC was able to predict disease progression better than the model that was based on sMC, uMC, and BMPC without serum B2M (C statistics, 0.760 vs 0.726). CONCLUSIONS: The current results indicated that 1) serum B2M is an independent predictor of asymptomatic MM progression, and 2) serum B2M adds prognostic information when combined with the most widely used prognosticators of asymptomatic MM progression.

1796 Poster Board I-822 The rationale of the study stems from three considerations: i) to date, few clinical predictors of asymptomatic multiple myeloma (MM) progression are available; ii) no study has assessed the role of beta-2-microglobulin (B2M) on risk of asymptomatic MM progression; iii) B2M is a serum marker of tumor burden and represents a key variable of the ISS staging system for symptomatic MM. The study aims at assessing the impact of B2M on risk of asymptomatic MM progression. The study was based on a consecutive series of 148 asymptomatic MM diagnosed according to the IMWG. Cumulative probability of progression to symptomatic MM was calculated from diagnosis of asymptomatic MM to progression to symptomatic disease according to IMWG. Survival analysis was performed by Kaplan-Meier method using log-rank to test for associations. Cox proportional hazard regression was used to build a multivariate model. Harrell's c-statistics was used to evaluate the discriminatory value of the prognostic models. Clinical features at asymptomatic MM diagnosis were as follows: median age 67 years, male:female ratio 1.02, previous MGUS 32/148 (21.6%), IgG monoclonal component (MC) 113/148 (76.4%), IgA MC 32/148 (21.6%), light chain MC 3/148 (2.0%), median serum monoclonal component (sMC) 1.1 g/dl, positive urinary immunofixation 27/148 (18.2%), median urinary monoclonal component (uMC) 98 mg/24h, median bone marrow plasma cell percentage (BMPC%) 15%, median B2M 2.0 mg/l, median albumin 4.3 g/dl, median C reactive protein 0.3 mg/l. After a median follow-up of 48 months, 29/148 asymptomatic MM progressed to symptomatic disease, accounting for a 29.5% 5-year probability of progression. According to Youden's index, best cut-off values for prediction of progression were 2.5 mg/l for B2M, 1.5 g/dl for sMC, 500 mg/24h for uMC, and 20% for BMPC%. Univariate analysis identified B2M >2.5 mg/l (5-year risk: 64.5%; HR=3.85; p<.001), sMC >1.5 g/dl (5-year risk: 49.1%; HR=5.76; p<.001), uMC >500 mg/24h (5-year risk: 68.7%; HR=6.60; p<.001) and BMPC% ≥20% (5-year risk: 50.2%; HR=5.77; p<.001) as predictors of progression to symptomatic MM. Clinical variables not associated with progression to symptomatic MM (p≥0.05 in all cases) were age, sex, sMC type, polyclonal Ig reduction, albumin, C reactive protein, Hb, calcium, creatinine, and previous MGUS. Multivariate analysis identified B2M >2.5 mg/l (HR=3.57; p=.001) as an independent predictor of progression to symptomatic MM, along with sMC >1.5 g/dl (HR=4.07; p=.003), uMC >500 mg/24h (HR=3.66; p=.015) and BMPC% ≥20% (HR=3.20; p=.007). Based on multivariate analysis, B2M, sMC, uMC, and BMPC% were combined into a model for predicting progression to symptomatic MM. This model stratified patients into four risk groups: very low risk (0 risk factors: 5-year risk 0%), low-intermediate risk (1 risk factor: 5-year risk 19.6%), high-intermediate risk (2 risk factors 5-year risk: 60.7%), and high risk (3 or 4 risk factors 5-year risk 80.7%) (Fig. 1). Three lines of evidence suggest that B2M may improve the conventional risk stratification model for prediction of asymptomatic MM progression defined by sMC, uMC, and BMPC%. First, B2M >2.5 mg/l adds prognostic information within the low risk group characterized by sMC '1.5 g/dl, uMC '500 mg/24h and BMPC <20% (p=.005), by segregating a very low risk group of patients with B2M<2.5 mg/l who never progressed (5-year risk: 0%). Second, B2M >2.5 mg/l adds prognostic information within the high risk group defined by sMC >1.5 g/dl and/or uMC >500 mg/24h and/or BMPC ≥20% (p=.034) by segregating a high risk group of patients with B2M >2.5 mg/l who are virtually all projected to progress (5-year risk: 89.0%). Third, based on c-statistics, the prognostic model including B2M along with sMC, uMC, and BMPC% (c-statistics=.760; SE=.045) allowed to predict asymptomatic MM progression better than a model based only on sMC, uMC, and BMPC% (c-statistics=.726; SE=.049). The implications of our results are twofold: i) B2M predicts progression of asymptomatic MM to symptomatic disease independent of conventional risk factors (sMC, BMPC%, light chain burden); ii) B2M refines the conventional model for predicting progression to symptomatic MM by allowing the identification of a very low risk group of patients who never progress and a high risk group of patients who are virtually all projected to progress. Disclosures No relevant conflicts of interest to declare.

Non-traumatic musculoskeletal complaints are often dealt with by emergency room (ER) physicians. We aimed to quantify how many patients with such complaints have conditions requiring immediate recognition and treatment, versus specialist referral, versus primary care. We retrieved the clinical records of all the patients admitted to the ER department of our hospital along 1 year. Pediatric (age <14 years) and obstetrics/gynecology cases were excluded. Data from all patients visiting the ER for non-traumatic musculoskeletal complaints were classified as follows: true emergencies (i.e., conditions associated with high morbidity/mortality risk), urgencies (i.e., conditions requiring prompt referral to a specialist), and non-urgent conditions (to be dealt with in primary care). Out of 54,915 patients evaluated in the ER of our hospital, 1652 patients complained of non-traumatic musculoskeletal symptoms (3.0 %): Back pain accounted for 944/1652 ER visits (57.1 %), including 6 emergencies (0.6 %) and 105 urgent conditions (11.1 %). Among the remaining 708 patients (42.9 %) who presented with complaints concerning a peripheral joint, true emergencies were 2/708 (0.3 %) while 210/708 were urgent conditions (29.7 %). Although patients who present to ER physicians with musculoskeletal complaints have rarely true emergencies, many of them are in need of urgent treatment and prompt specialist referral.