Finite element techniques for the Navier-Stokes equations in the primitive variable formulation and the vorticity stream-function formulation

Finite element procedures for the Navier-Stokes equations in the primitive variable formulation and the vorticity stream-function formulation have been implemented. For both formulations, streamline-upwind/Petrov-Galerkin techniques are used for the discretization of the transport equations. The main problem associated with the vorticity stream-function formulation is the lack of boundary conditions for vorticity at solid surfaces. Here an implicit treatment of the vorticity at no-slip boundaries is incorporated in a predictor-multicorrector time integration scheme. For the primitive variable formulation, mixed finite-element approximations are used. A nine-node element and a four-node + bubble element have been implemented. The latter is shown to exhibit a checkerboard pressure mode and a numerical treatment for this spurious pressure mode is proposed. The two methods are compared from the points of view of simulating internal and external flows and the possibilities of extensions to three dimensions

Monomorphic epitheliotropic intestinal T-cell lymphoma comprises morphologic and genomic heterogeneity impacting outcome.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare aggressive T-cell lymphoma most reported in Asia. We performed a comprehensive clinical, pathological and genomic study of 71 European MEITL patients (36 males; 35 females, median age 67 years). The majority presented with gastrointestinal involvement and had emergency surgery, and 40% had stage IV disease. The tumors were morphologically classified into two groups: typical (58%) and atypical (i.e. nonmonomorphic or with necrosis, angiotropism or starry-sky pattern) (42%), sharing a homogeneous immunophenotypic profile (CD3+ (98%) CD4- (94%) CD5- (97%) CD7+ (97%) CD8+ (90%) CD56+ (86%) CD103+ (80%) cytotoxic marker+ (98%)) with more frequent expression of TCRgd (50%) than TCRab (32%). MYC expression (30% of cases) partly reflecting MYC gene locus alterations, correlated with nonmonomorphic cytology. Almost all cases (97%) harbored deleterious mutation(s) and/or deletion of the SETD2 gene and 90% had defective H3K36 trimethylation. Other frequently mutated genes were STAT5B (57%), JAK3 (50%), TP53 (35%) JAK1 (12.5%), BCOR and ATM (11%). Both TP53 mutations and MYC expression correlated with atypical morphology. The median overall survival (OS) of 63 patients (43/63 only received chemotherapy after initial surgery) was 7.8 months. Multivariate analysis found a strong negative impact on outcome of MYC expression, TP53 mutation, STAT5B mutation and poor performance status while aberrant B-cell marker expression (20% of cases) correlated with better survival. In conclusion, MEITL is an aggressive disease with resistance to conventional therapy, predominantly characterized by driver gene alterations deregulating histone methylation and JAK/STAT signalling and encompasses genetic and morphologic variants associated with very high clinical risk

Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma : Long-Term Results of the PRIMA Study

PURPOSE The PRIMA study (ClinicalTrials.gov identifier: NCT00140582) established that 2 years of rituximab maintenance after first-line immunochemotherapy significantly improved progression-free survival (PFS) in patients with follicular lymphoma compared with observation. Here, we report the final PFS and overall survival (OS) results from the PRIMA study after 9 years of follow-up and provide a final overview of safety. METHODS Patients (> 18 years of age) with previously untreated high-tumor-burden follicular lymphoma were nonrandomly assigned to receive one of three immunochemotherapy induction regimens. Responding patients were randomly assigned (stratified by induction regimen, response to induction treatment, treatment center, and geographic region) 1:1 to receive 2 years of rituximab maintenance (375 mg/m(2), once every 8 weeks), starting 8 weeks after the last induction treatment, or observation (no additional treatment). All patients in the extended follow-up provided their written informed consent (data cutoff: December 31, 2016). RESULTS In total, 1,018 patients completed induction treatment and were randomly assigned to rituximab maintenance (n = 505) or observation (n = 513). Consent for the extended follow-up was provided by 607 patients (59.6%) of 1,018 (rituximab maintenance, n = 309; observation, n = 298). After data cutoff, median PFS was 10.5 years in the rituximab maintenance arm compared with 4.1 years in the observation arm (hazard ratio, 0.61; 95% CI, 0.52 to 0.73; P <.001). No OS difference was seen in patients randomly assigned to rituximab maintenance or observation (hazard ratio, 1.04; 95% CI, 0.77 to 1.40; P = .7948); 10-year OS estimates were approximately 80% in both study arms. No new safety signals were observed. CONCLUSION Rituximab maintenance after induction immunochemotherapy provides a significant long-term PFS, but not OS, benefit over observation.Peer reviewe

Long-term survival of patients with CLL after allogeneic transplantation: A report from the European Society for Blood and Marrow Transplantation

PubMed ID: 27941763Even with the availability of targeted drugs, allogeneic hematopoietic cell transplantation (allo-HCT) is the only therapy with curative potential for patients with CLL. Cure can be assessed by comparing long-term survival of patients to the matched general population. Using data from 2589 patients who received allo-HCT between 2000 and 2010, we used landmark analyses and methods from relative survival analysis to calculate excess mortality compared with an age-, sex- and calendar year-matched general population. Estimated event-free survival, overall survival and non-relapse mortality (NRM) 10 years after allo-HCT were 28% (95% confidence interval (CI), 25-31), 35% (95% CI, 32-38) and 40% (95% CI, 37-42), respectively. Patients who passed the 5-year landmark event-free survival (N=394) had a 79% probability (95% CI, 73-85) of surviving the subsequent 5 years without an event. Relapse and NRM contributed equally to treatment failure. Five-year mortality for 45- and 65-year-old reference patients who were event-free at the 5-year landmark was 8% and 47% compared with 3% and 14% in the matched general population, respectively. The prospect of long-term disease-free survival remains an argument to consider allo-HCT for young patients with high-risk CLL, and programs to understand and prevent late causes of failure for long-term survivors are warranted, especially for older patients. © 2017 Macmillan Publishers Limited, part of Springer Nature

Rituximab plus Lenalidomide in Advanced Untreated Follicular Lymphoma

Rituximab plus chemotherapy has been shown to be effective in patients with advanced-stage, previously untreated follicular lymphoma; nevertheless, most patients will have a relapse. Combination immunotherapy with lenalidomide and rituximab is an immunomodulatory regimen that has shown promising activity in patients with indolent B-cell non-Hodgkin's lymphoma

Long-term survival of patients with CLL after allogeneic transplantation: A report from the European Society for Blood and Marrow Transplantation

Even with the availability of targeted drugs, allogeneic hematopoietic cell transplantation (allo-HCT) is the only therapy with curative potential for patients with CLL. Cure can be assessed by comparing long-term survival of patients to the matched general population. Using data from 2589 patients who received allo-HCT between 2000 and 2010, we used landmark analyses and methods from relative survival analysis to calculate excess mortality compared with an age-, sex- and calendar year-matched general population. Estimated event-free survival, overall survival and non-relapse mortality (NRM) 10 years after allo-HCT were 28% (95% confidence interval (CI), 25-31), 35% (95% CI, 32-38) and 40% (95% CI, 37-42), respectively. Patients who passed the 5-year landmark event-free survival (N=394) had a 79% probability (95% CI, 73-85) of surviving the subsequent 5 years without an event. Relapse and NRM contributed equally to treatment failure. Five-year mortality for 45- and 65-year-old reference patients who were event-free at the 5-year landmark was 8% and 47% compared with 3% and 14% in the matched general population, respectively. The prospect of long-term disease-free survival remains an argument to consider allo-HCT for young patients with high-risk CLL, and programs to understand and prevent late causes of failure for long-term survivors are warranted, especially for older patients