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Patients with acute decompensated heart failure (ADHF) are frequently treated with unnecessary antibiotics since they are confused with pneumonia patients.To study the efficacy of measuring C-reactive protein (CRP) levels on admission and CRP velocity in differentiating ADHF from pneumonia.A retrospective observational study of ADHF and pneumonia patients admitted to a tertiary hospital during 2 years. Patients who were already treated with antibiotics on admission were excluded. Efficacy of CRP as a diagnostic marker was evaluated by using receiver operator curves (ROC).Overall, 72 ADHF and 50 pneumonia patients were included in the study. The mean CRP levels on admission were 13.5+/-13.5 mg/L for the ADHF patients and 127+/-84 mg/L for the pneumonia patients (p0.001). CRP increases ofor =0.56 mg/L/h were diagnostic of pneumonia. CRP levels on admission together with CRP increases had a sensitivity of 0.96 and a specificity of 0.972 (p0.001) as markers to distinguish pneumonia from ADHF.This study emphasizes the dynamic nature of biomarkers. Demonstrating the efficiency of repeated CRP measurements in an acute setting will provide clinicians with a valuable tool for establishing the correct diagnosis and refraining from unnecessary use of antibiotics.

BACKGROUND/ AIM: The prognostic significance of hyperleukocytosis in chronic lymphocytic leukemia (CLL) remains uncertain. The aim of the present study was to evaluate the clinical characteristics and outcome of patients with CLL and white blood count (WBC)150×10(6)/l at the time of diagnosis.Using the database of the Israeli CLL Study Group, which includes 1,507 cases, we identified 41 patients diagnosed with WBC150×10(6)/l and analyzed the survival in the group that was 62 months compared to 174 months in patients without hyperleukocytosis (p0.001). However, multivariate analysis demonstrated that the WBC count had no predictive value in relation to survival time. While in the entire patient cohort advanced age and Binet stage, presence of thrombocytopenia and ZAP-70 expression were independently associated with poor prognosis, these parameters lost their prognostic value in patients with hyperleukocytosis.Although our results do not confirm that high initial levels of WBC are independently associated with shorter survival in CLL, the clinical course in these cases appears to be aggressive and conventional prognostic factors are not valid in this patient sub-group.

Background Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare disease. In the absence of consensus guidelines, treatment is controversial. Here, we describe the characteristics and outcomes of consecutive NLPHL patients diagnosed at Memorial Sloan Kettering Cancer Center (MSKCC) with a focus on active surveillance (AS) as a first-line management strategy. Methods We included consecutive patients aged 16 years (y) or older who were diagnosed and followed at MSKCC between 1974 and 2016. All cases were confirmed by a MSKCC hematopathologist as NLPHL without evidence of transformation. We excluded composite lymphomas and patients with any prior hematological malignancy or concomitant active cancer. We compared outcomes between patients followed expectantly (AS) and those treated actively (AT), which included radiotherapy (RT) only, chemotherapy (+/- Rituximab) (CT), combined modality (+/- Rituximab) (CMT), and rituximab monotherapy (R). Progression-free survival (PFS) was defined as time from diagnosis to a biopsy-proven disease progression or relapse, initiation of further treatment or death. PFS2 was defined as time from diagnosis to second biopsy-proven disease progression or relapse, initiation of 3rd-line treatment or death. AS was considered a 1st-line treatment. We used univariable and multivariable survival analyses stratifying patients by disease stage. Results In total, 163 patients were included. The median follow-up was 5.7y (Min-Max: 0.3 - 42.7) with 24.5% (n=40) of patients followed for 10y or more. Patient characteristics for all, AS and AT patients are shown in Table 1. Patients were treated with RT only (n=75, 46.0%), AS (n=37, 22.7%), CT (n=26, 15.9%), CMT (n=19, 11.7%) or R alone (n=6, 3.7%). Overall, outcome of patients was excellent, with 10-year PFS, PFS2 and overall survival (OS) estimates of 71.2% [95%-CI: 59.3-80.1], 92.5% [95%-CI: 83.7-96.6] and 96.6% [95%-CI: 87.6-99.1], respectively. Seven patients died, 3 deaths were likely treatment related and only one lymphoma related death occurred after progression. Twelve transformations to aggressive lymphomas occurred after a median of 7.0y (Min-Max: 0.4 - 15.6). The transformation rate was 0.99% per patient year. Twelve secondary cancers occurred after a median of 7.8y (Min-Max: 1.1 - 24.8). Only bulky disease ≥ 5 cm (n=21, HR: 3.1 [95%-CI: 1.3-7.2], p=0.008) and extranodal disease (n=11, HR: 7.7 [95%-CI: 2.1-28.5], p=0.002] were risk factors for a shorter PFS in the final multivariate model after correcting for received treatment. In pairwise comparison, PFS with CMT (p=0.038) and RT (p=0.032) was superior to AS, but CT was not (p>0.999). PFS2 and OS were not significantly different between groups. Patients, who received AT (n=126) overall tended to have superior PFS than those in the AS group (n=37) (5-year PFS 97.2% [95%-CI: 79.2-92.2] vs. 76.5% [95%-CI: 55.7-88.5], p=0.068), though this benefit was mainly seen in early stage disease (Ann Arbor I/II) (5-year PFS 94.2% [95%-CI: 86.7-97.6] vs. 65.1% [95%-CI: 43.5-80.2], p Conclusion NLPHL has an excellent prognosis. Bulky and extranodal disease were identified as potential risk factors for progression. With the limitations of a retrospective analysis, it can be concluded that AS is a viable management strategy in NLHPL. The majority of AS patients require no treatment after multiple years of observation and those that do, can be adequately managed with established treatments. Additionally, no evidence was found for an increased rate of transformation or worse PFS2 or OS in AS patients. Treatment related deaths exceeded deaths from lymphoma. Figure 1 Figure 1. Disclosures Moskowitz: Celgene: Consultancy; Genentech BioOncology: Consultancy; Seattle Genetics: Consultancy, Other: Ad Board, Research Funding; Merck: Consultancy, Research Funding; Pharmacyclics: Research Funding. Zelenetz: Genentech/Roche, GSK, Gilead, Celgene, Janssen, Hospira, Amgen, Takeda Pharma, Novartis, Nanostring Technologies, Portola Pharmaceuticals, Adaptive Biotechnology: Consultancy; GSK, Janssen, Roche, Gilead, Bristol Myers: Research Funding; Boehringer Ingelheim: Other: DMC Membership. Kumar: Seattle Genetics: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees. Moskowitz: Incyte: Research Funding; Bristol Myers-Squibb: Consultancy, Research Funding; Seattle Genetics: Honoraria, Research Funding; Takeda: Honoraria; ADC Therapeutics: Research Funding.

Clinical databases may contain several records for a single patient. Multiple general entity-resolution algorithms have been developed to identify such duplicate records. To achieve optimal accuracy, algorithm parameters must be tuned to a particular dataset. The purpose of this study was to determine the required training set size for probabilistic, deterministic and Fuzzy Inference Engine (FIE) algorithms with parameters optimized using the particle swarm approach. Each algorithm classified potential duplicates into: definite match, non-match and indeterminate (i.e., requires manual review). Training sets size ranged from 2,000–10,000 randomly selected record-pairs. We also evaluated marginal uncertainty sampling for active learning. Optimization reduced manual review size (Deterministic 11.6% vs. 2.5%; FIE 49.6% vs. 1.9%; and Probabilistic 10.5% vs. 3.5%). FIE classified 98.1% of the records correctly (precision=1.0). Best performance required training on all 10,000 randomly-selected record-pairs. Active learning achieved comparable results with 3,000 records. Automated optimization is effective and targeted sampling can reduce the required training set size.

Introduction Clinical databases require accurate entity resolution (ER). One approach is to use algorithms that assign questionable cases to manual review. Few studies have compared the performance of common algorithms for such a task. Furthermore, previous work has been limited by a lack of objective methods for setting algorithm parameters. We compared the performance of common ER algorithms: using algorithmic optimization, rather than manual parameter tuning, and on two-threshold classification (match/manual review/non-match) as well as single-threshold (match/non-match). Methods We manually reviewed 20 000 randomly selected, potential duplicate record-pairs to identify matches (10 000 training set, 10 000 test set). We evaluated the probabilistic expectation maximization, simple deterministic and fuzzy inference engine (FIE) algorithms. We used particle swarm to optimize algorithm parameters for a single and for two thresholds. We ran 10 iterations of optimization using the training set and report averaged performance against the test set. Results The overall estimated duplicate rate was 6%. FIE and simple deterministic algorithms allowed a lower manual review set compared to the probabilistic method (FIE 1.9%, simple deterministic 2.5%, probabilistic 3.6%; p

Although duplicate records are a potential patient safety hazard, the actual clinical harm associated with these records has never been studied. We hypothesized that duplicate records will be associated with missed abnormal laboratory results.A retrospective, matched, cohort study of 904 events of abnormal laboratory result (HgbA1c, TSH, Vitamin B(12), LDL). We compared the rates of missed laboratory results between patients with duplicate and non-duplicate records from the ambulatory clinics. Cases were matched according to test and ordering physician.Duplicate records were associated with a higher rate of missed laboratory results (OR=1.44, 95% CI 1.1-1.9). Other factors associated with missed lab results were tests performed as screening (OR=2.22, 95% CI 1.4-3.4), and older age (OR=1.15 for every decade, 95% CI 1.01-1.2). In most cases test results were reported into the main patient record.Duplicate records were associated with a higher risk of missing important laboratory results.

Background: Prognosis of follicular lymphoma (FL) has long been defined by the FLIPI score (Solal-Céligny et al., 2004) which is a 5 factor risk model consisting of age, stage, lactate dehydrogenase, hemoglobin and number of nodal areas. The FLIPI model has been validated at diagnosis in both the pre- and post-Rituximab eras. However, many patients are initially observed and have prolonged lead time from diagnosis to first treatment. In this study, we investigated whether FLIPI risk group at diagnosis changed by the time of initial treatment, and whether change of FLIPI risk group impacted treated outcome. Patients and Methods: All adult (≥18 yo) patients with de novo follicular lymphoma (FL) treated at our center between 1998 and 2007 were evaluated. Study excluded patients with ≤2 follow up visits, known divergent of composite histology at diagnosis, and active concurrent malignancies. FLIPI was scored at diagnosis and at initiation of first treatment. For patients with missing FLIPI data, FLIPI category was scored if the omission did not alter the FLIPI category. Stable FLIPI risk group was defined as FLIPI score being low or intermediate at diagnosis and at initiation of first treatment (Low-Low, Int-Int). Progressed FLIPI risk group was defined by the population which changed categories from low or intermediate at diagnosis to a higher category at initiation of treatment (Low-Int, Low-High, Int-High). FLIPI scores were available for 570 patients at both diagnosis and initial treatment. Overall survival (OS) and progression free survival (PFS) were evaluated by Kaplan-Meier method and compared by log-rank tests. Time of diagnosis was used as time origin for OS analyses. When OS analyses involved FLIPI score at the first treatment, time of the first treatment was used as the entry time to adjust the risk sets to account for the fact that FLIPI at first treatment is unknown before the onset of the first treatment. Chi-squared tests and Fisher's exact tests were used to compare categorical variables by FLIPI score change status. Progression free survival before and after 24 months (PFS24) of initial therapy were calculated. Results: For 898 FL patients, median follow up was 9.2 years (range 0.23 - 16.84), median OS not reached. Based on FLIPI at diagnosis, the 5 year OS is 97.2% for low risk, 93.0% for int risk, and 80.2% for high risk, 10 yr OS is 90.9% for low risk, 77.7% for int risk, and 67.6% for high risk. Of 570 patients with FLIPI at diagnosis and first treatment, median time to first treatment was 0.18 years (range 0-12.5) for patients with stable FLIPI (N=280) and 2.70 years (range 0.01-13.33) for patients with progressed FLIPI (N=83). For patients observed ≥ 6 and 12 months, the median time to first treatment was 1.21 years (N=47, range 0.51-12.5) and 2.49 years (N=29, range 1.0-12.5) for patients with stable FLIPI and 3.77 years (N=62, range 0.54-13.3) and 3.92 years (N=57, range 1.13-13.3) for patients with progressed FLIPI, respectively. Progressed FLIPI was observed in 14.6% (83/570) of patients. The incidence of progressed FLIPI was 51.4% (57/111) in patients observed ≥1 year before initiating therapy. Parameters contributing to progressed FLIPI compared to stable FLIPI were decreased hemoglobin (29% versus 6%), increased nodal areas affected (43% versus 2%) and higher LDH (37% versus 5%). Patients with stable FLIPI had longer PFS at 12 and 24 months, 88.6% versus 73.8% (P=0.006) and 79.3% versus 66.1% (P= 0.031) (Figure 1). Analysis of patients initially observed ≥ 6 or 12 months demonstrated that progressed FLIPI negatively affected OS and PFS (Figure 2, observed ≥ 12 month data not shown). Median PFS for patients observed ≥ 6 months was 8.36 years for stable FLIPI, 3.14 years for progressed FLIPI. At observation of ≥ 12 months, median PFS was 6.25 and 3.22 years for stable and progressed FLIPI, respectively. Increased FLIPI was associated with increased risk of transformation throughout the disease course (25% vs 16%, P=0.039). Conclusion: Progressed FLIPI between diagnosis and first line treatment is associated with a reduced PFS, and increased incidence of histologic transformation. In patients who are initially observed, a progressed FLIPI reduces OS and PFS. The effect on PFS may be related to treatment bias and ongoing analysis is underway. Progressed FLIPI potentially identifies a population with heightened risk of transformation. Disclosures Hamlin: Seattle Genetics: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Portola: Research Funding; Novartis: Research Funding; Molecular Templates: Research Funding; Xencor: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Horwitz:Seattle Genetics: Consultancy, Research Funding; Celgene: Consultancy; Huya: Consultancy; Infinity: Consultancy, Research Funding; Kyowa Hakka Kirin: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; ADCT Therapeutics: Research Funding; Spectrum: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy. Kumar:Celgene: Honoraria, Other: Scientific Advisory Board; Pharmacyclics: Research Funding; Seattle Genetics: Research Funding; Adaptive Biotechnologies: Research Funding; Celgene: Research Funding. Moskowitz:Bristol Myers Squibb: Honoraria; Merck: Honoraria; Seattle Genetics: Honoraria, Research Funding. Moskowitz:Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Palomba:Pharmacyclics: Consultancy. Zelenetz:Gilead Sciences: Research Funding.

Introduction In their lifetime, patients with follicular lymphoma frequently require multiple treatments, which have improved their survival over the past few decades. The expected treatment outcome based on lines of treatment in the post-Rituximab era is currently unknown. We analyzed the progression free survival and event free survival by line of treatment to aid estimating clinical endpoints when designing future clinical trials for multiply relapsed patients. Patients and Methods Adults (≥18 years) with de novo follicular lymphoma (FL) treated at our center between 1998 and 2007 were eligible (N=1134). 236 patients with ≤2 visits, mixed histology at initial diagnosis, and active concurrent malignancy were excluded. Of the remaining 898 patients, 105 were observed and did not require treatment during the timeframe of this dataset, and 2 had incomplete data, therefore 791 patients were eligible for response, progression and event free survival (PFS and EFS) analysis (Figure 1). Response was documented by investigators based on clinical or radiographic assessment. Complete response was based on radiographic assessment. PFS was defined as start of treatment to progression of disease or death. Patients with inadequate response to treatment, change of treatment, or stable disease without subsequent documented relapse were censored in the PFS analysis. Events for EFS were defined as progression, change of treatment, and death. PFS and EFS of sequential lines of treatment were evaluated by Kaplan-Meier method and compared across lines using log-rank test with adjustment for within-patient correlation. PFS and EFS were compared by other clinical variables using regular log-rank tests. Results Median age of diagnosis was 57.3 years with 1:1 male to female ratio. Median overall survival was not reached with median follow up of 9 years (N=898, range 0.2 - 16.8 years, Figure 1A). Median time to first treatment for the entire group was 2.3 months (range 0 - 13.3 years). In first line treatment of the 791 patients, 51% (N=406) received Rituximab with chemotherapy (R-Chemo), 13% (N=101) received chemotherapy only (Chemo), 19% (N=150) received Rituximab monotherapy (R-Mono), and 17% (N=129) received other treatments including radiation and surgery. For second line treatment, 405 patients were treated with about 37% receiving R-Chemo and 34% receiving R-Mono. As line of treatment increased, the percentage of patients with radiographically assessed complete response diminished from 71% at first line treatment to 25% by fifth line treatment (Figure 1B). Median PFS for first, second and third line treatment are 4.8, 1.6, and 1 year, respectively (Figure 2A). Median EFS for first, second and third line treatment are 3.8, 1.1, 0.8 year, respectively (Figure 2B). For subsequent lines of treatment, both median PFS and EFS were Conclusion Follicular lymphoma is an indolent disease often requiring multiple lines of treatment. However, PFS and EFS for multiple lines of treatment in FL has not been described in the post-Rituximab era. The work has benchmarked the median response by line of treatment. After third line treatment, the PFS was ≤1 year. This analysis serves to aide comparison of different therapies for future drug approval in relapsed FL. Disclosures Hamlin: Xencor: Membership on an entity's Board of Directors or advisory committees; Portola: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Molecular Templates: Research Funding; Novartis: Research Funding; Seattle Genetics: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees. Horwitz:Spectrum: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy; Huya: Consultancy; Infinity: Consultancy, Research Funding; Kyowa Hakka Kirin: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Celgene: Consultancy; ADCT Therapeutics: Research Funding. Kumar:Celgene: Honoraria, Other: Scientific Advisory Board; Celgene: Research Funding; Adaptive Biotechnologies: Research Funding; Seattle Genetics: Research Funding; Pharmacyclics: Research Funding. Moskowitz:Merck: Honoraria; Seattle Genetics: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria. Moskowitz:Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Palomba:Pharmacyclics: Consultancy. Zelenetz:Gilead Sciences: Research Funding.

Distinguishing community acquired pneumonia (CAP) from chronic obstructive pulmonary disease (COPD) exacerbation is a challenging task, since fever, productive cough, dyspnea, and leukocytosis are all common features of both conditions. Moreover, chest X-ray might not be sensitive enough. It is therefore quite common for physicians to prescribe unnecessary antibiotics for COPD exacerbation, leading to resistant bacteria and other related adverse affects.To study whether CRP levels upon admission and the delta in CRP levels following initiation of antibacterial treatment, could provide an efficient tool for distinguishing CAP from COPD exacerbation.The study group included 36 COPD exacerbation and 49 CAP patients, admitted to a single Internal Medicine department during the years 2004-2006. All patients were treated with cephalosporins and macrolides upon admission.CRP levels upon admission were significantly higher among CAP patients than among COPD exacerbation patients (111.5+/-104.4 vs. 34.9+/-28.6 mg/l, p0.0001). CRP levels on the second day of hospitalization, following antibiotic administration to all patients, made a sharp incline in 36.7% of CAP patients compared to only 5.9% of COPD exacerbation patients (p=0.005), and remained unchanged in 61.8% of COPD patients compared to 16.3% of CAP patients (p=0.0006).CRP levels upon admission and the delta in CRP levels following initiation of antibacterial treatment could provide an efficient tool for distinguishing CAP from COPD exacerbation.

Introduction: Autologous Stem Cell Transplantation (ASCT) has become the cornerstone of managing relapsed lymphomas. However, its use in elderly patients or those with comorbidities is limited because of high regimen related toxicities (RRT). Several chemotherapy regimens have been suggested to minimize RRT while maintaining the antitumor effect. TECAM (Thiotepa 160 mg/m2 over 4 days , Etoposide and Cytarabine 800mg/m2 over 4 days, Cytoxan 60 mg/kg, and Melphalan 120 mg/m2 over 2 days) is a reduced toxicity modification for the commonly used BEAM protocol. Aim: This study aimed to compare the safety and efficacy or the TECAM regimen with that of its more intense BEAM counterpart. Methods: A retrospective cohort study of all patients who underwent ASCT for treatment of lymphoma with either BEAM or TECAM conditioning regimens at the Tel Aviv Medical Center between October 1999 and January 2014. We compared early (≤100 days) mortality, RRT rate, time to engraftment and length of hospitalization as well as overall and progression free survival. Results: A total of 146 patients (76 BEAM, 70 TECAM) were included in the analysis. Median follow up was 47 months. Patient treated with TECAM were older (54.5 vs. 45.5, p=0.001), and nearly 20% (n=13) of them had dose reductions (average 17±7%), as opposed to a single patient in the BEAM arm. Conversely, TECAM patients had a longer time interval from first diagnosis to transplant (22 vs. 13 months, p There was no statistically significant difference in PFS (26 months vs. not reached, TECAM vs. BEAM, p=0.16), nor in OS (not reached for both, p=0.55). In multivariable analysis the only factor associated with PFS was not entering transplantation in CR (HR 2.4, 95% CI 1.4-4.0, p=0.001). Similarly, factors associated with OS were older age (HR 1.023, 95% CI 1.004-1.043 per year, p=0.016) and non-CR at transplantation (HR 2.4, 95% CI 1.4-4.4, p=0.003). Discussion: We found comparable results for BEAM and its low toxicity counterpart TECAM. There were no differences in early mortality, RRT, time to engraftment, PFS, or OS. This was despite the fact that patients treated with TECAM were, on average, nine years older, and probably perceived to be frailer as indicated by a considerably higher rate of dose reductions. This study has several limitations that extend beyond its retrospective single institution nature. It encompasses a heterogeneous group of lymphomas, and there was possibly a selection bias allocating patients with a more severe disease to BAEM. Regardless, it suggests that TECAM could provide a lower toxicity alternative for ASCT conditioning in a selected group of patients. Table 1. Baseline characteristics BEAM (n=76) TECAM (n=70) p vlaue Age* 45.5 [29.5-54.0] 54.5 [41.3-65.0] 0.001 Sex (female) 31 (40.8%) 32 (45.7%) 0.67 Lymphoma type 0.09 Diffuse large B cell 32 (42.1%) 35 (50.7%) Hodgkin's 15 (19.7%) 15 (21.7%) T Cell 16 (21.1%) 4 (5.80%) Follicular 3 (3.95%) 6 (8.70%) Mantle cell 7 (9.21%) 8 (11.6%) Other 3 (3.95%) 1 (1.45%) Months from diagnosis* 13 [9-22] 22 [12-37] Figure 1. Overall and progression free survival Figure 1. Overall and progression free survival Disclosures Rozovski: Novartis: Other: Advisory board.

Introduction: Rising levels of plasma creatinine in the setting of acute unilateral ureteral obstruction (AUUO) often reflects acute renal failure, mandating kidney drainage. We hypothesize that reabsorption of peri-renal urine extravasation (PUE), a common result of UUO, contributes significantly to the elevation in plasma creatinine, rendering the latter an inaccurate benchmark for renal function. We explored this hypothesis in a rat model of AUUO and PUE.Methods: In total, 20 rats were equally divided into 4 groups. Groups 1 and 2 underwent unilateral ligation of the ureter with infiltration of rat’s urine (index group) or saline (control) into the peri-renal space. Two additional control groups underwent perirenal injection of either urine or saline without AUUO. Plasma creatinine levels were determined immediately prior to the procedure (T0), and hourly for 3 hours (T1, T2 and T3). Renal histology was investigated after 3 hours.Results: Rats in the index group had a significantly greater increase in plasma creatinine levels over 3 hours compared to all other groups (p < 0.05). At T3, average plasma creatinine levels for the index group increased by 96% (0.49 ± 0.18 mg/dL) compared to 46% (0.23 ± 0.06 mg/dL increase) in the AUUO and saline group, and less than 15% rise in both the non-obstructed control groups. Our study limitations includes lack of spontaneous PUE and intraperitoneal surgical approach.Conclusions: Absorption of peri-renal urine in the presence of AUUO is a significant contributor to rising plasma creatinine levels, beyond those attributable to the obstruction alone, and may overestimate the extent of the true renal functional impairment.

INTRODUCTION Botezomib-based induction is widely used and highly effective for the treatment of patients with newly diagnosed multiple myeloma (NDMM), with an overall response rate (ORR) of 75-80%. However, the outcomes of patients who fail to respond to this treatment remain unclear. The goal of this study was to investigate the outcome of patients with NDMM who failed to respond to bortezomib-based induction as compared to induction-responsive patients. METHODS We reviewed consecutive patients with NDMM between 1-JAN-2007 and 31-JAN-2014 in three participating centers in Greece and Israel. Inclusion criteria were measurable disease and an induction regimen containing bortezomib in combination with alkylators and/or corticosteroids. Patients who failed to achieve at least partial response in accordance with IMWG criteria after 4 cycles of therapy were classified as non-responsive and their baseline characteristics, next treatment, overall survival and progression following second-line treatment (2ndPFS) were assessed and compared to responsive patients. 2ndPFS was defined as the time from 2nd line treatment to disease progression, death or censoring. In the non-responsive group we limited this analysis to patients advancing to 2nd line within six months of initiation of induction. RESULTS Two hundred and ninety five patients met inclusion criteria and 74 (25%) were non-responsive to bortezomib-containing induction. Non-responsive patients were older, more anemic and had more often ISS-3, del17p and ECOG performance status 2-4 (table 1). Notably, these patients received less often a bi-weekly bortezomib schedule, a triple-drug regimen and high dose melphalan treatment at first line. Of the non-responsive patients 57% (n=42) received salvage treatment immediately following induction non-response, with an ORR of 59% (25/42); 12/31(39%) of those treated with salvage 2nd line and 13/15(87%) of those who underwent HDM at first line, responded. Failure to respond to bortezomib induction was associated with increased mortality (HR 5.06, 95% CI 2.80 – 9.16) (Fig. a), which remained significant in multivariate analysis. One- and 3-years OS in responsive vs. non-responsive patients were 97% vs 76% and 88% vs 53%, respectively (p 2ndPFS in patients who received salvage second line therapy immediately following induction failure was similar to that measured in bortezomib-responsive patients receiving 2nd-line therapy for disease progression, approaching 14 months. However, survival from time of salvage 2nd-line treatment was significantly lower among patients non-responsive to bortezomib-based induction compared to that measured in responsive patients (25 months vs. not reached, respectively, p=0.024; Fig. b). CONCLUSIONS Failure to respond to a bortezomib-based induction was found to be an independent risk factor for mortality. Despite the non-inferior 2ndPFS reported in these patients as compared with their bortezomib-responsive counterparts, survival remained significantly inferior. Possibly this difference is because non-responsive patients are less likely to respond to further proteasome inhibitor therapy at following relapses. Randomized controlled trials are needed to test whether intensification of induction and/or of further treatment may improve the poor prognosis of patients who fail to respond to bortezomib-based induction. Table 1: All patients n = 295 Induction non-responsive n = 74 Induction - responsive n =221 P value Demographic Median Age (yrs) 62.0 66.8 61.0 0.004 Gender Male Female 148 (50%) 147 (50%) 42 (55%) 33 (45%) 107 (48%) 114 (52%) 0.347 Patient / Disease ECOG 0-1 2-4 182 (63%) 107 (37%) 33 (45%) 40 (55%) 149 (69%) 67 (31%) 2mg% 23 (14%) 69 (34%) 66 (27%) 23 (9.5%) 114 (43%) 64 (23%) 10 (26%) 13 (28%) 21 (36%) 5 (8.1%) 35 (54%) 20 (30%) 13 (10%) 56 (36%) 45 (24%) 18 (9.7%) 79 (39) 44 (21%) 0.031 0.297 0.091 0.805 0.044 0.094 Therapy Induction regimen VCD Vd VMP PAD 204 (69%) 49 (17%) 11 (4%) 19 (6%) 52 (57%) 18 (24%) 3 (4%) 4 (5%) 162 (73%) 31 (14%) 8 (4%) 15 (7%) 0.007 Any triplet 243 (82%) 55 (74%) 188 (85%) 0.051 Bortezomib schedule Bi-weekly Weekly 239 (81%) 56 (19%) 52 (70%) 22 (30%) 187 (85%) 34 (15%) 0.010 HDM at first line 143 (48%) 15 (20%) 128 (58%) Figure 1 Figure 1. Disclosures Dimopoulos: Celgene: Consultancy, Honoraria.

The combination of fludarabine, cyclophosphamide and rituximab (FCR) is still currently regarded as the standard regimen for treatment of physically fit patients with chronic lymphocytic leukemia (CLL). This therapy can be associated with significant toxicity, and patient adherence to the protocol may often be difficult outside of clinical trials. This retrospective study aimed to evaluate the efficacy and safety of FCR therapy in the “real life” setting, with particular focus on the influence of dose reduction on treatment outcome. A total of 132 CLL patients (≤70 years of age) treated with FCR as frontline therapy from 10 medical centers, were reviewed. The majority of patients were males (73.5%, n=97) and younger than 60 years (78%, n=103). Eleven patients had Binet stage A (8.3%), 72 (54.5%) were stage B and 49 (37.1%) had Binet stage C. Results of FISH analysis were available for 99 patients, with high risk cytogenetics of del(11q) in 21 patients (21.2%) and del(17p) in 9 cases (9.1%). The majority (56.5%, n=74) received rituximab at a dose of 500mg/m2 and the rest 375mg/m2. Almost half of the patients (49.2%, n=65) were given a reduced dose of chemotherapy ( In conclusion, it is apparent that outside of clinical trials treating physicians tend more readily to reduce doses of chemotherapy. Reduced doses of fludarabine and cyclophosphamide but not of rituximab, is significantly associated with a shorter PFS. Disclosures No relevant conflicts of interest to declare.

Background High-dimensional data obtained using modern molecular technologies (e.g., gene expression, proteomics) and large clinical datasets is increasingly common. Risk stratification based on such high-dimensional data remains challenging. Traditional statistical models have a limited capability of handling large numbers of variables, non-linear effects, correlations and missing data. More importantly, as more variables are analyzed, models tend to over-fit (i.e., the model provides good predictions on the studied data but performs poorly on other data). Recently two methods have been proposed for handling multivariate analysis of high-dimensional data. The Least Absolute Shrinkage and Selection Operator (LASSO) minimizes the number of Cox regression coefficients, favoring models that are parsimonious and less likely to over-fit. LASSO is computationally efficient and capable of handling correlated variables. Random Survival Forests (RSF) combines multiple decision trees built on randomly selected subsets of variables. This enables the evaluation of all variables, even in the presence of significant correlations or missing data, and reduces over-fitting. Few studies have evaluated these models on realistic datasets. This study compared the performance of LASSO and RSF to that of the traditional Cox Proportional Hazard (CoxPH) with respect to their ability to predict survival based on high dimensional reverse phase protein array (RPPA) data from Acute Myeloid Leukemia (AML) patients. Methods Our data were derived from previous work to define the role of the pathway activation in AML using a custom made RPPA onto which were printed leukemia enriched cells from 511 newly diagnosed AML patients collected between 1992 and 2007. The RPPA was probed with 231 strictly validated antibodies. Data were normalized and analysis was performed for the 415 subjects that underwent therapy at MD Anderson. The dataset also included 38 clinical variables. We removed cases with a documented survival of less than 4 weeks and imputed a small number of sporadically missing values by random sampling with replacement. We generated LASSO, RSF, and CoxPH models using R. We built RSF models using 1000 trees and 10 random split points. We then identified key features using the RSF max-subtree and the glmnet cross validation methods. We built an RSF and Cox models to these variables only. Models were trained on a bootstrap sample of the size of the dataset, randomly sampled with replacement, and tested on the un-sampled remaining cases. The process was repeated for 50 iterations and results were averaged. We report Harrell’s concordance index (C-Index) and the Brier score for model performance. Harrell’s C-Index is a pairwise comparison of all observations in the testset. It evaluates the probability of erroneously assigining longer survival time to one case over the other. Brier score calculates the difference between the predicted and observed probabilities. It evaluates how well the model fits the entire dataset. Results Cox regression with LASSO regularization had the best performance based on both Brier score and C-Index (Table 1 and figure 1). For the complete dataset Cox regression models did not converge even when using forward feature selection. Cox regression following feature selection based on RSF had inferior performance compared to other methods. Conclusions LASSO and RSF allow for mutlivariate analysis of high-dimensional data that would have not been possible otherwise. LASSO regularization outperforms other methods in terms of accuracy and to select features for traditional Cox models. Using the latter approach has great appeal as traditional Cox models allow easy interpertation of the hazard associated with individual variables. Differences in Brier scores are more pronounced than C-Indexes, possibly indicating a tendency of LASSO regularization to overfit the data compared to RSF. Disclosures: No relevant conflicts of interest to declare.

Article-at-a-Glance Background After-hours telephone communications are common in patient management. Patterns of communication of key information during after-hours phone calls were evaluated, and the utility of problem-specific Situation, Background, Assessment, Recommendation (SBAR) forms in improving this communication was assessed. Methods In a randomized trial using a simulated on-call setting, 20 nurses called physicians regarding six cases adapted from inpatient records and based on the six most common reasons for after-hours nurse-physician communication. Three of the cases were handled without the SBAR forms (control cases), and three cases were handled with the forms (SBAR cases). Two cue types of communication were evaluated: situation cues, which conveyed the patient's situation (for example, a patient is confused), and background cues, which conveyed problem-specific data indicated on the SBAR forms (for example, the patient has a low sodium level). Results Ninety-two phone calls were analyzed (43 SBAR/49 controls). Most of the nurses reported the situation cues (SBAR 88%, control 84%, p = .60) but not the background cues. There was a trend toward fewer background cues communicated in the SBAR cases (14% versus 31%, p = .08). In 14% of the cases, on average, nurses omitted information or reported wrong information regarding the background cue. Physicians asked questions that resulted in the communication of the cues in a minority of the cases when the background cues were not originally provided by the nurses (SBAR 6%, control 16%, p = .39). Conclusions In after-hours phone communication between physicians and nurses, significant information was often not communicated and physicians did not elicit the necessary information. Simply providing an SBAR–based form did not ensure complete communication of key information.