Safety and efficacy of cyclophosphamide, adriamycin, vincristine, prednisone and rituximab in patients with human immunodeficiency virus-associated diffuse large B-cell lymphoma: results of a phase II trial

Immunochemotherapy with cyclophosphamide, adriamycin, vincristine, prednisone and rituximab (R-CHOP) is the standard treatment in non-immunosuppressed patients with diffuse large B-cell lymphoma (DLBCL), but its adequacy has not been definitively established in patients with human immunodeficiency virus (HIV)-related lymphoma. This phase II trial aimed to evaluate the safety and efficacy of six cycles of R-CHOP in patients with HIV-related DLBCL and to determine whether response to highly active antiretroviral therapy (HAART) had prognostic impact. Patients were eligible if they had performance status <3 and absence of active opportunistic infections. Eighty-one patients were enrolled, 57 in stages III or IV, International Prognostic Index (IPI) 0 or 1 ( n  = 26), 2 ( n  = 19), 3 ( n  = 20) and 4 or 5 ( n  = 16), and median CD4 lymphocyte count of 0·158 × 10⁹/l. The main adverse events were neutropenia (48% of cycles) and infections (10% of cycles), which were fatal in seven patients. Complete response was achieved in 55 (69%) patients, with an estimated 3-year disease-free survival of 77% and 3-year overall survival of 56%. IPI score and virological response to HAART were the prognostic parameters for response and survival. In HIV-related DLBCL R-CHOP is feasible, safe and effective. The prognosis depends on lymphoma-related parameters and on the response to HAART.     

Axillary artery cannulation with a Dacron graft for surgery of the aortic arch and ascending aorta

Cannulation of the axillary artery is one possible means of establishing cardiopulmonary bypass during surgery of the ascending aorta and aortic arch. Use of a Dacron graft for cannulation has a number of advantages. In this article, we report our experience with this technique in seven consecutive patients in whom we performed an ascending aorta replacement. The associated procedures involved were aortic root reconstruction using David's procedure in two patients, the Bentall procedure in one, the hemi-arch technique in two, the complete arch and elephant trunk technique in one, aortic valve repair in one, and Valsalva sinus reconstruction in one. Circulatory arrest with antegrade cerebral perfusion was carried out in three cases. There was no in-hospital mortality, and there were no vascular or infectious complications related to axillary access. One patient presented with transient paresthesia of the brachial plexus. In all cases, cardiopulmonary bypass flow was adequate.     

Lewis Histo-Blood Group System and Associated Secretory Phenotypes

This review summarises present knowledge of the chemistry, immunology, genetics and clinical significance of antibodies in the Lewis and secretor histoblood group systems. Although red cell serology has laid the foundations for these systems, more recent advances have been made by studying Lewis and related glycoconjugates with monoclonal antibodies, determining structures by mass spectrometry and NMR spectroscopy, identifying enzymes and their specificities, and identifying the genes by molecular biology. The expression of Lewis system antigens is dependent on Lewis and secretor loci. Fucosyltransferases coded by genes at these loci compete and interact with each other and with other transferases to determine an individual's Lewis and secretor phenotype. Exocrine epithelial cells, mostly of endodermal origin, synthesise the Lewis antigens which, as plasma glycolipids, are secondarily acquired by cells of the peripheral circulation. Phenotyping red cells is often regarded as a simple way of determining the Lewis and sometimes the secretor status of an individual; however, the red cell phenotype is influenced by many factors and may not necessarily reflect someone's Lewis and secretor genotypes. Two main red cell Lewis groups are usually found, Lewis negative and Lewis positive. In Lewis-negative individuals, the secretor genotype does not affect the Lewis phenotype, but in Lewis-positive individuals, the non-secretor genotype generates the Le(a+b–) phenotype, the secretor genotype causes the Le(a–b+) phenotype, and the partial secretor genotype gives rise to the Le(a+b+) phenotype.     

Clinical significance of post‐prophylaxis cytomegalovirus infection in lung transplant recipients

Cytomegalovirus (CMV ) disease has been associated with the development of chronic lung allograft dysfunction (CLAD ) after transplantation. However, the relevance of CMV replication occurring after the discontinuation of antiviral prophylaxis on the development of CLAD has not been fully established. Patients who underwent lung transplantation during 2004‐2014 were included. All patients received antiviral prophylaxis for 3‐6 months, followed by monitoring of CMV replication during the first year post‐transplantation (preemptive therapy). Risk factors for the development of CLAD were assessed by Cox models. A linear regression model with an interaction coefficient between time and CMV infection was used to evaluate the influence of CMV infection on the evolution of FEV ₁. Overall, 69 patients were included, 30/69 (43%) patients developed at least 1 episode of significant CMV infection, and 8/69 (11.5%) patients developed CMV disease. After a median follow‐up of 3.67 years, 25/69 (36%) patients developed CLAD and 14/69 (20%) patients died. In the univariate Cox analysis, significant CMV infection (HR 1.177, P  = .698), CMV disease (HR 1.001, P  = .998), and duration of CMV replication (HR 1.004, P  = .758) were not associated with CLAD . Only bacterial pneumonia tended to be associated with CLAD in the multivariate model (HR 2.579, P  = .062). We did not observe a significant interaction between CMV replication and evolution FEV ₁ (interaction coefficient 0.006, CI 95% [?0.084 to 0.096], P  = .890). In this cohort of lung transplant recipients receiving antiviral prophylaxis and monitored by preemptive therapy post‐prophylaxis, CMV infection did not have impact on long‐term allograft lung function.     

Concurrent intensive chemotherapy and imatinib before and after stem cell transplantation in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. Final results of the CSTIBES02 trial

Background

Imatinib, given concurrently or alternating with chemotherapy, has improved the response and survival of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph⁺ ALL) but relapses are still frequent. The aim of this study was to evaluate the feasibility and results of giving imatinib concurrently with intensive chemotherapy, stem cell transplantation and post-transplant imatinib maintenance therapy in patients with newly diagnosed Ph⁺ ALL.

Design and Methods

This was a phase II study of patients with newly diagnosed Ph⁺ ALL given standard chemotherapy, together with imatinib (400 mg/day) until stem cell transplantation, followed by imatinib maintenance therapy for all patients regardless of the molecular status of the disease.

Results

Of the 30 patients included, 27 (90%) achieved complete remission, one was resistant to treatment and two died during induction therapy. The percentages of major and complete molecular responses were 86% and 21% after induction, and 81% and 65% after consolidation, respectively. Similar results were observed assessing minimal residual disease by flow cytometry. Of the 27 patients who achieved complete remission, 21 underwent stem cell transplantation (16 allogeneic, 5 autologous). Imatinib (400 mg/day) could be administered after transplantation for a median of 3.9 months in 12 patients, although it was interrupted in 10 patients (in 2 cases because of side effects of the drug). Nine patients relapsed, four before and five after stem cell transplantation and eight patients died of transplant-related causes. With a median follow-up of 4.1 years, the probabilities (95% CI) of disease-free and overall survival were 30% (15% to 45%) and 30% (16% to 45%), respectively.

Conclusions

These results confirm that imatinib is an effective first-line treatment for adult Ph⁺ ALL when given concurrently with chemotherapy, making stem cell transplantation feasible in a high proportion of patients. However, post-transplantation imatinib administration was limited, mainly because of transplantation-derived complications rather than drug-specific toxicity.     

An Observational Study of the Effect of Levodopa–Carbidopa Intestinal Gel on Activities of Daily Living and Quality of Life in Advanced Parkinson’s Disease Patients

Introduction

Continuous delivery of levodopa–carbidopa intestinal gel (LCIG) by percutaneous endoscopic gastrojejunostomy (PEG-J) in advanced Parkinson’s disease (PD) patients reduces variability in plasma levels, providing better control of motor fluctuations (“on” and “off” states). The MONOTREAT study assessed the effect of LCIG on activities of daily living, motor and non-motor symptoms, and quality of life in advanced PD patients.

Methods

This prospective, observational study included patients with advanced, levodopa-responsive PD with either 2–4 h of “off” time or 2 h of dyskinesia daily. Patients received LCIG via PEG-J for 16 h continuously. Effectiveness was assessed using Unified PD Rating Scale parts II and III, the Non-Motor Symptom Scale, and the PD Questionnaire-8.

Results

The mean (SD) treatment duration was 275 (157) days. Patients experienced significant improvement from baseline in activities of daily living at final visit (p < 0.05) as well as at months 3 and 6 (p < 0.0001). Patients also experienced significant improvements from baseline in quality of life and non-motor symptoms at all time points (p < 0.001 for all). Specifically, patients manifested significant improvements in mean change from baseline at every study visit in five of nine non-motor symptom score domains: sleep/fatigue, mood/cognition, gastrointestinal tract, urinary, and miscellaneous. One-third of patients (32.8%) experienced an adverse event; 21.9% experienced a serious adverse event; 11.1% discontinued because of an adverse event.

Conclusion

This study demonstrated significant and clinically relevant improvements in measures of activities of daily living, quality of life, and a specific subset of non-motor symptoms after treatment with LCIG.

Funding

AbbVie Inc.

     

Pólipos gástricos: análisis retrospectivo de 41.253 endoscopias digestivas altas

Introduction

Gastric polyps are usually asymptomatic lesions incidentally discovered during endoscopy.