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Genetic alterations causing constitutive activation of the nuclear factor kappa B (NF-κB) signaling pathway has been associated with the development of lymphomas. A20 (TNFAIP3) is a key regulator of NF-κB signaling. Its suppressor functions are often inactivated by deletions and/or mutations in various hematologic malignancies. Since we recently found the rs143002189 polymorphism in the A20 loci in our multiple myeloma samples, we further investigated this polymorphism in different lymphoid neoplasias. For this purpose, we tested 479 cases of the most common B cell malignancies for the presence of the rs143002189 polymorphism. We found a significant higher occurrence of the rs143002189 polymorphism in diffuse large B cell lymphoma (DLBCL) compared to non-neoplastic controls and other types of B cell malignancies. Furthermore, structure analyses of the mutated A20 protein led to the assumption that the new steric interaction within the protein is responsible for a reduced or inactivated A20 protein. Our data indicates that in a significant fraction of patients, rs143002189 might contribute to the development of DLBCL. [ABSTRACT FROM AUTHOR]

The International Prognostic Index ( IPI) has been used for decades in diffuse large B-cell lymphoma ( DLBCL). A retrospective cancer registry analysis in North America showed significantly improved results when an enhanced IPI, the National Comprehensive Cancer Network ( NCCN)- IPI was applied. This novel score puts more weight on age and high levels of lactate dehydrogenase ( LDH). Nevertheless, it remains unclear if these results can be extrapolated to the general population. This retrospective bi-centre analysis included 499 unselected DLBCL patients who were treated with rituximab and anthracycline-based chemoimmunotherapy between 2004 and 2013. In our cohort, the NCCN- IPI was more accurate in identifying patients at low or high risk, despite older age, and more patients with increased LDH. Nevertheless, a modified scoring of the risk factors was required to more accurately identify elderly patients with a very favourable diagnosis, suggesting an impaired value of the original NCCN- IPI in the elderly. Serum β2-microglobulin and albumin were retained as independent prognostic factors for survival in a multivariate analysis. Our data confirm, for the first time, the superior prognostic power of the NCCN- IPI in an unselected, middle-European cohort. We furthermore propose a modified NCCN- IPI for more accurate prognostication in the elderly. Albumin and β2-microglobulin levels are likely to add significant information to the NCCN- IPI. [ABSTRACT FROM AUTHOR]

Central nervous system recurrence in acute lymphoblastic leukemia (ALL) occurs in up to 15% of patients and is frequently associated with poor outcome. The purpose of our study was to evaluate the efficacy and safety of a slow-release liposomal formulation of cytarabine for intrathecal (IT) meningeal prophylaxis in patients suffering from ALL. Forty patients aged 20-77 years (median 36) were preventively treated with a total of 96 (range 1-6) single doses containing 50 mg of liposomal cytarabine on a compassionate use basis. After a median observation period of 23 months (range 2-118) only two patients experienced a combined medullary-leptomeningeal disease recurrence after primary diagnosis. Except for headache grade 2 in two patients, no specific toxicity attributable to IT liposomal cytarabine application was noted. Long-term neurological side effects were not observed. IT liposomal cytarabine therapy with concomitant dexamethasone appears to be feasible and well tolerated. [ABSTRACT FROM AUTHOR]

Testing for serum galactomannan (GM) has been established as an important method for diagnosing invasive aspergillosis (IA); however, limited data exist regarding the application of urine GM testing. The objective of this study was to evaluate the performance of GM screening of urine specimens and to compare results with serum GM. The study was performed between July 2012 and March 2013 in adult patients with underlying hematological malignancies who were hospitalized at the Medical University of Graz, Austria. Serum and urine screening samples were collected and tested twice weekly (always on the same day). In total, 242 serum samples and a similar number of urine samples were collected from 75 patients. A total of 21/242 (8.7%) serum samples from 13 patients were GM positive. Sensitivity, specificity, positive predictive value, and negative predictive value using a 0.1 optical density index cutoff for urine samples (compared with same-day serum results) were as follows: 47.6%, 86%, 24.4%, and 94.5%, respectively. In 8/10 patients with probable IA, at least one positive GM result was found with this cutoff. After calculating clinical performance of the urine GM test, we found that sensitivity increased to 71.4% and specificity to 88.2%. Spearman–Rho correlation analysis revealed a significant positive correlation between serum and urine samples (P < 0.001; ρ = 0.252). In conclusion, GM detection in urine might be a promising method for IA screening. However, further studies are needed. [ABSTRACT FROM PUBLISHER]

Genetic alterations causing constitutive activation of the nuclear factor kappa B (NF-κB) signaling pathway has been associated with the development of lymphomas. A20 (TNFAIP3) is a key regulator of NF-κB signaling. Its suppressor functions are often inactivated by deletions and/or mutations in various hematologic malignancies. Since we recently found the rs143002189 polymorphism in the A20 loci in our multiple myeloma samples, we further investigated this polymorphism in different lymphoid neoplasias. For this purpose, we tested 479 cases of the most common B cell malignancies for the presence of the rs143002189 polymorphism. We found a significant higher occurrence of the rs143002189 polymorphism in diffuse large B cell lymphoma (DLBCL) compared to non-neoplastic controls and other types of B cell malignancies. Furthermore, structure analyses of the mutated A20 protein led to the assumption that the new steric interaction within the protein is responsible for a reduced or inactivated A20 protein. Our data indicates that in a significant fraction of patients, rs143002189 might contribute to the development of DLBCL.

Extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT) type represent 7-8% of all B cell lymphomas and up to 50% of primary gastric lymphomas and can arise at any extranodal site. The most common manifestation is the stomach, which is almost invariably associated with a chronic Helicobacter pylori infection. The diagnosis is based on the histopathological evaluation of multiple gastric biopsies in accordance with the current WHO classification. The mainstay of therapy is H. pylori eradication, which must be delivered to all gastric MALT lymphoma patients, independent of stage. In patients who do not achieve lymphoma regression following antibiotic therapy, irradiation and/or systemic oncological therapies should be applied, depending on the stage of the disease. Radiotherapy might be the preferred option for localized stage. However, in the presence of disseminated or advanced disease, chemotherapy and/or immunotherapy with the anti-CD 20 antibody rituximab is the treatment of choice, but no standard chemotherapy has been defined so far. Gastric MALT lymphomas have a limited tendency to distant spreading and to histological transformation and thus MALT lymphoma usually has a favorable outcome, with an overall survival rate at 5 years of more than 85%., (© 2014 S. Karger AG, Basel.)

Diffuse large B-cell lymphoma (DLBCL) is the most commonly-occurring type of non-Hodgkin lymphoma and is considered a curable disease in at least 50% of patients. Considering that the disease represents a heterogeneous group of tumors, recent efforts using gene expression profiling have identified two subgroups, with significantly different response rates to standard immunochemotherapy. Nevertheless, multiple factors in the pathogenesis of this disease remain unclear and continue to be the focus of further research. MicroRNAs are small non-coding RNA molecules that regulate gene expression at the post-transcriptional level. The role of microRNAs in cancer initiation and progression has been demonstrated in multiple types of solid cancers and hematological malignancies such as lymphomas. MicroRNAs also have diagnostic potential, and therapeutic of microRNAs targeting is actively pursued. This review provides an overview on the role of microRNAs in the diagnosis of diffuse large B-cell lymphoma, their role in molecular pathogenesis and hence their prospective role in implementing novel future treatment options.