The new oral anticoagulants dabigatran etexilate (Pradaxa), rivaroxaban (Xarelto), and apixaban (Eliquis) have predictable pharmacokinetic and pharmacodynamic profiles and are alternatives to warfarin. However, many physicians are wary of these drugs, since there is limited evidence on how to manage bleeding in patients taking them, and since no specific antidote is known to reverse their anticoagulant effect. Management requires careful adherence to first principles of bleeding care. Unapproved and untested reversal strategies may be required in patients with life-threatening bleeding.
Introduction Diffuse large B cell lymphoma (DLBCL) accounts for approximately 30% of the non-Hodgkin’s lymphomas. However, DLBCL has heterogeneous clinical, histological, and molecular features. It has been identified that the clinical features and the treatment response vary with genetic and molecular features that affect disease aggressiveness. Gene rearrangements and more recently protein expressions involving MYC, BCL2 or BCL6 have been shown to have major prognostic implications. Lymphomas with recurrent chromosomal breakpoints activating multiple oncogenes, (one being MYC), are often referred to as “Double hit” lymphomas (DHL). Objectives The current study aims to identify patients with DLBCL for the presence of co-expression of proteins involving MYC with BCL2 and/or BCL6, corresponding translocations and their prognostic impact on response to therapy and overall survival. Methods Patients were retrospectively identified by reviewing tumor registries and pathology records at the Cleveland Clinic Health system for any of the diagnoses between January 1998 and December 2011: Burkitt-like lymphoma; Aggressive B-cell lymphoma NOS; “B-cell lymphoma unclassifiable with features intermediate between DLBCL and Burkitt's lymphoma”; High-grade B-cell lymphoma; Diffuse large B-cell lymphoma with aggressive features and Diffuse aggressive lymphoma NOS. Data collected included Clinical characteristics at the time of diagnosis, Immunohistochemistry, Cytogenetics, type of treatment received, response in terms of complete and partial remission and survival data. Patients aged < 18 years and with the diagnosis of low grade lymphoma and Burkitt's lymphoma were excluded from the study. Results Data from 65 patients diagnosed between June 2001 and February 2012 were available for analysis. Overall 52% of patients were male, median age at diagnosis was 69 yrs (range 36-89 yrs), and most had good ECOG performance status (82% ECOG 0, 1). Most patients had DLBCL (83%), and majority of the patients were stage 3 or 4 (63%). The most common sites of extranodal disease were bone marrow (26%), followed by Genitourinary (15%), and muscle (15%). The majority of patients were in the International Prognostic Index (IPI) poor risk group (53%) Positive MYC protein expression or translocation was found in 16 (24%) patients. 7 patients had DHL with 5 patients having MYC/BCL2 translocations, 1 patient-MYC/BCL6 and 1 patient with MYC/BCL2/ BCL6 ( Triple hit) translocations. 9 patients had MYC protein expression with or without translocation with co-expression of either BCL2 or BCL6 protein. 81% (53/65) of patients had BCL2 expression (14 had translocation), 65% (42/65) had BCL6 expression (7 had translocation), and 24% (16/65) had MYC protein expression (12 had translocation). 25 patients (38%) had a single protein expression; of which 14 patients had BCL2, 10 patients had BCL6 and 1 patient had MYC. 24 patients (37%) were positive for both BCL2 and BCL6 co-expression; of which 5 patients had positive translocations by FISH. 61 % (40/65) of the patients did not have FISH studies following immunohistochemistry. Overall 92% (60/65) of patients received systemic treatment, primarily RCHOP (73%). Only 54 patients had follow up data after treatment. 59% of the patients achieved a complete remission (CR), 22% had a best response of partial remission (PR), and 17% did not respond to treatment. 30 patients (54%) died with an estimated median overall survival of 58.9 months (26.6-127.7 months). As with response to chemotherapy, patients with a single protein expression with either BCL2 or BCL6, or co-expression with both BCL2/BCL6 had similar outcomes in terms of overall survival (79.9 vs 70.6 months) and CR (70% vs. 79%). Whereas, patients with protein expression/ translocation involving MYC tended to have poorer outcomes: 19% (3/16) had CR ( p=.0005) and estimated median survival of 11.5 months (p=.005). Conclusion Diffuse large B cell lymphomas involving co-expression of MYC protein with BCL2 or BCL6 have a significantly lower survival rate compared to the patients with single protein expression of BCL2 or BCL6 as well as co-expression of BCL2 and BCL6. In addition to obtaining cytogenetic studies, we emphasize the need to conduct prospective clinical trials which can aim at the optimal treatment strategies for this subset of DLBCL patients expressing the MYC proto-oncogene with BCL2 and/or BCL6 proteins. Disclosures: No relevant conflicts of interest to declare.
2076 Background: Low-grade gliomas account for 10-20% of all primary brain tumors. There is limited data on specific prognostic factors for patients with low-grade gliomas. Methods: After obtaining IRB approval, the Cleveland Clinic Brain Tumor and Neuro-Oncology Center’s database was used to identify patients with histologically confirmed grade 2 glioma at the time of diagnosis. Multivariable analysis was conducted with use of a Cox proportional hazards model and a stepwise selection algorithm that used p<0.10 as the criteria for entry and p<0.05 as retention in the model to identify independent predictors of survival. Results: Chart records of 478 patients (54% of whom were men) diagnosed between 1991 and 2010 were included for analysis. The median age at presentation was 41 years (range, 18-83 years). 42% of patients had biopsy only, 27% had gross total resection, 6% had near total resection, and 25% had subtotal resection. 22% of patients were initially treated with radiation, 30% with adjuvant chemotherapy, and 7% with concurrent chemotherapy. Median progression free survival and median overall survival (OS) were 5.1 years and 12.8 years, respectively. On multivariate analysis, independent of additional therapy, five factors were identified as independent predictors of OS: age at diagnosis (p=0.002), Karnofsky performance status (KPS, p<0.0001), histology (astrocytoma vs. other, p=0.001), hemispheric location (left or bilateral involvement vs. right, p=0.02) and gender (male vs. female, p=0.0003). Conclusions: Older age, male gender, poor performance status, astrocytic histology, and left hemispheric or bilateral involvement are associated with higher mortality. [Table: see text]
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