AR. Front-line, dose-escalated immunochemotherapy is associated with a significant PFS (but not OS) advantage in 401 patients (pts) with double-hit lymphomas (DHL): A systematic review and meta-analysis. Blood, 124, abst 3056). Summary'Double-hit lymphomas' (DHL), defined by concurrent MYC and BCL2 (or, alternatively, BCL6) rearrangements, have a very poor outcome compared to standard-risk, diffuse large B-cell lymphomas (DLBCL). Consequently, dose-intensive (DI) therapies and/or consolidation with high-dose therapy and transplant have been explored in DHL, although benefit has been debated. This meta-analysis compared survival outcomes in DHL patients receiving dose-escalated regimens [DI: R-Hyper-CVAD (rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone) or R-CO-DOX-M/IVAC (rituximab, cyclophosphamide, doxorubicin, vincristine, methotrexate/ifosfamide, etoposide, high dose cytarabine); or intermediatedose: R-EPOCH (rituximab, etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone)] versus standard-dose regimens (R-CHOP; rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) in the firstline setting. Data were synthesized to estimate hazard ratios of dose-escalated treatments versus R-CHOP using a Weibull proportional hazards model within a Bayesian meta-analysis framework. Eleven studies examining 394 patients were included. Patients were treated with either front-line R-CHOP (n = 180), R-EPOCH (n = 91), or R-Hyper-CVAD/rituximab, methotrexate, cytarabine (R-M/C), R-CODOX-M/R-IVAC (DI) (n = 123). Our meta-analysis revealed that median progression-free survival (n = 350) for the R-CHOP, R-EPOCH and DI groups was 12Á1, 22Á2, and 18Á9 months, respectively. First-line treatment with R-EPOCH significantly reduced the risk of a progression compared with R-CHOP (relative risk reduction of 34%; P = 0Á032); however, overall survival (n = 374) was not significantly different across treatment approaches. A subset of patients might benefit from intensive induction with/without transplant. Further investigation into the role of transplant and novel therapy combinations is necessary.Keywords: front-line, dose-escalated, immunochemotherapy, progressionfree survival, double-hit lymphomas. A number of prognostic factors have been reported in patients with diffuse large B-cell lymphoma (DLBCL) and follicular large-cell lymphoma. Among them, the presence of chromosomal rearrangements involving the oncogene MYC in combination with BCL2 and/or, less frequently, BCL6 (Kramer et al, 1998;Johnson et al, 2012) is by far the most significant in defining the subset of double-hit lymphoma (DHL) patients who have poor survival outcomes.Although the DHL phenotype determined by immunohistochemistry (IHC) has been reported in up to 20-30% of DLBCL, the frequency of true DHL defined by chromosomal rearrangements constitutes only about 8-10% of all DLBCL (Petrich et al, 2014a). The combination of cellular proliferation induced by MYC with the antiapoptotic effect conferred by BCL2 rearrangement in DHL p...

Objectives: Coronary computerized tomographic angiography (CTA) has high correlation with cardiac catheterization and has been shown to be safe and cost-effective when used for rapid evaluation of lowrisk chest pain patients from the emergency department (ED). The long-term outcome of patients discharged from the ED with negative coronary CTA has not been well studied. Methods:The authors prospectively evaluated consecutive low-to intermediate-risk patients who received coronary CTA in the ED for evaluation of a potential acute coronary syndrome (ACS). Patients with cocaine use, known cancer, and significant comorbidity reducing life expectancy and those found to have significant disease (stenosis ‡ 50% or ejection fraction < 30%) were excluded. Demographics, medical and cardiac history, labs, and electrocardiogram (ECG) results were collected. Patients were followed by telephone contact and record review for 1 year. The main outcome was 1-year cardiovascular death or nonfatal acute myocardial infarction (AMI).Results: Of 588 patients who received coronary CTA in the ED, 481 met study criteria. They had a mean (±SD) age of 46.1 (±8.8) years, 63% were black or African American, and 60% were female. There were 53 patients (11%) rehospitalized and 51 patients (11%) who received further diagnostic testing (stress or catheterization) over the subsequent year. There was one death (0.2%; 95% confidence interval [CI] = 0.01% to 1.15%) with unclear etiology, no AMI (0%; 95% CI = 0 to 0.76%), and no revascularization procedures (0%; 95% CI = 0 to 0.76%) during this time period.Conclusions: Low-to intermediate-risk patients with a Thrombosis In Myocardial Infarction (TIMI) score of 0 to 2 who present to the ED with potential ACS and have a negative coronary CTA have a very low likelihood of cardiovascular events over the ensuing year.ACADEMIC EMERGENCY MEDICINE 2009; 16:693-698 ª

Purpose: Lenalidomide, an immunomodulatory agent that enhances antibody-dependent cell-mediated cytotoxicity, has the potential to synergize with rituximab, an anti-CD20 mAb. We hypothesized that the addition of lenalidomide to rituximab would improve clinical outcomes in patients with B-cell lymphomas who were previously rituximab resistant, defined as no response to or progression of lymphoma within 6 months of rituximab-based therapy.Experimental Design: We conducted a single-center, phase II trial in patients with indolent B-cell or mantle cell lymphomas who were previously rituximab resistant. Patients received 10 mg lenalidomide daily for 8 weeks, and then received four weekly doses of 375 mg/m 2 rituximab; lenalidomide continued during and after rituximab. Response to therapy was assessed after 8 weeks of lenalidomide and 12 weeks after first dose of rituximab. The primary endpoint was overall response rate (ORR) after lenalidomide and rituximab.Results: Fifty patients were enrolled and 43 patients completed both response assessments. ORR after 8 weeks of lenalidomide was 30.2%; 12 weeks after the addition of rituximab to lenalidomide, ORR increased to 62.8% (N ¼ 43). For all patients (N ¼ 50), median progression-free survival (PFS) is 22.2 months (median follow-up, 39.2 months). PFS after lenalidomide-rituximab was significantly longer than the PFS for the antecedent regimen used to define rituximab resistance (22.2 vs. 9.13 months, P ¼ 0.0004).Conclusions: This trial is the first to show that the combination of lenalidomide and rituximab overcomes prior rituximab resistance in patients with indolent B-cell and mantle cell lymphomas.

Objectives: Observational studies of patients with cocaine-associated myocardial infarction have suggested more coronary disease than expected on the basis of patient age. The study objective was to determine whether cocaine use is associated with coronary disease in low-to intermediate-risk emergency department (ED) patients with potential acute coronary syndrome (ACS). Methods:The authors conducted a cross-sectional study of low-to intermediate-risk patients < 60 years of age who received coronary computerized tomographic angiography (CTA) for evaluation of coronary artery disease (CAD) in the ED. Patients were classified into three groups with respect to CAD: maximal stenosis <25%, 25% to 49%, and ‡50%. Prespecified multivariate modeling (generalized estimating equations) was used to assess relationship between cocaine and CAD.Results: Of 912 enrolled patients, 157 (17%) used cocaine. A total of 231 patients had CAD ‡ 25%; 111 had CAD ‡ 50%. In univariate analysis, cocaine use was not associated with a lesion 25% or greater (12% vs. 14%; relative risk [RR] = 0.89, 95% confidence interval [CI] = 0.5 to 1.4) or 50% or greater (12% vs. 11%; RR = 1.15, 95% CI = 0.6 to 2.3). In multivariate modeling adjusting for age, race, sex, cardiac risk factors, and Thrombosis in Myocardial Infarction (TIMI) score, cocaine use was not associated with the presence of any coronary lesion (adjusted RR = 0.95, 95% CI = 0.69 to 1.31) or coronary lesions 50% or greater (adjusted RR = 0.78, 95% CI = 0.45 to 1.38). There was also no relationship between repetitive cocaine use and coronary calcifications or between recent cocaine use and CAD.