Prolonged survival of patients with angioimmunoblastic T-cell lymphoma after high-dose chemotherapy and autologous stem cell transplantation: the GELTAMO experience

Abstract OBJECTIVES: Angioimmunoblastic T-cell lymphoma (AIL) is a rare lymphoma with a poor prognosis and no standard treatment. Here, we report our experiences with 19 patients treated with high-dose chemotherapy and autologous stem cell transplantation (HDC/ASCT) within the GELTAMO co-operative group between 1992 and 2004. METHODS: The median age at transplantation was 46 yr. Fifteen patients underwent the procedure as front-line therapy and four patients as salvage therapy. Most patients received peripheral stem cells (90%) coupled with BEAM or BEAC as conditioning regimen (79%). RESULTS: A 79% of patients achieved complete response, 5% partial response and 16% failed the procedure. After a median follow-up of 25 months, eight patients died (seven of progressive disease and secondary neoplasia), while actuarial overall survival and progression-free survival at 3 yr was 60% and 55%. Prognostic factors associated with a poor outcome included bone marrow involvement, transplantation in refractory disease state, attributing more than one factor of the age-adjusted-International Prognostic Index, Pretransplant peripheral T-cell lymphoma (PTCL) Score or Prognostic Index for PTCL. CONCLUSIONS: More than half of the patients with AIL that display unfavourable prognostic factors at diagnosis or relapse would be expected to be alive and disease-free after 3 yr when treated with HDC/ASCT. Patients who are transplanted in a refractory disease state do not benefit from this procedure

Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice

Chromosomal translocations involving the MALT1 gene are hallmarks of mucosa-associated lymphoid tissue (MALT) lymphoma. To date, targeting these translocations to mouse B cells has failed to reproduce human disease. Here, we induced MALT1 expression in mouse Sca1(+)Lin(-) hematopoietic stem/progenitor cells, which showed NF-κB activation and early lymphoid priming, being selectively skewed toward B-cell differentiation. These cells accumulated in extranodal tissues and gave rise to clonal tumors recapitulating the principal clinical, biological, and molecular genetic features of MALT lymphoma. Deletion of p53 gene accelerated tumor onset and induced transformation of MALT lymphoma to activated B-cell diffuse large-cell lymphoma (ABC-DLBCL). Treatment of MALT1-induced lymphomas with a specific inhibitor of MALT1 proteolytic activity decreased cell viability, indicating that endogenous Malt1 signaling was required for tumor cell survival. Our study shows that human-like lymphomas can be modeled in mice by targeting MALT1 expression to hematopoietic stem/progenitor cells, demonstrating the oncogenic role of MALT1 in lymphomagenesis. Furthermore, this work establishes a molecular link between MALT lymphoma and ABC-DLBCL, and provides mouse models to test MALT1 inhibitors. Finally, our results suggest that hematopoietic stem/progenitor cells may be involved in the pathogenesis of human mature B-cell lymphomas

Centrality evolution of the charged-particle pseudorapidity density over a broad pseudorapidity range in Pb-Pb collisions at root s(NN)=2.76TeV

Peer reviewe

Implementation of a Physical Activity Program Protocol in Schoolchildren: Effects on the Endocrine Adipose Tissue and Cognitive Functions

JM-F was supported by a Postdoctoral Contract (Perfeccionamiento de Doctores) from the University of Granada.Practicing exercise is one of the best strategies to promote well-being and quality of life, however physical activity in schoolchildren and adolescents is developed in an unpredictable, intermittent way and in short periods. There are relatively few intervention studies investigating the role of physical activity in schoolchildren endocrine function of adipose tissue and cognitive function. One hundred and three boys, divided into two groups: control (n = 51, did not perform additional physical activity) and exercise (n = 52, performed vigorous physical activity after the regular school classes). The exercise group, developed a 6 months physical activity protocol delivered by the physical education teacher during the second semester of the academic course (6 months). Body composition measurements, adherence to the Mediterranean diet, nutritional intake, hematological and biochemical parameters, endocrine function of the adipose tissue and biomarkers of brainmolecular function were assessed at enrolment and after 6months of intervention. No statistically significant differences between both groups were found for age, height and bone mass. Weight and BMI was lower in the exercise group compared to the control group, increasing lean mass and reducing fat mass. 58.68% of children in the exercise group showed high adherence to the Mediterranean Diet compared to 46.32% of the control group. The exercise group was more concerned about their diet consumed more fiber, vitamin B1, B2, B6, B12, D, Niacin, Folic acid, Fe, Zn, Se and Cu. Triglycerides levels and HDL-cholesterol were higher in the exercise group at the end of the study. Leptin, MCP-1, lipocalin-2, adipsin and PAI-1 levels were lower in the exercise group at the end of the exercise protocol. In contrast, adiponectin and osteocrin markedly increased in the exercise group. Moreover, marked increases were recorded in healthy brain state biomarkers (NGF, BDNF, and irisin) in the exercise group, which could have a positive impact on academic performance. Taken together, all the findings reported are consistent with many benefits of the exercise protocol on adipose tissue and brain molecular function, demonstrating the usefulness of early interventions based on physical activity in children to reduce risk factors related to sedentary lifestyle.Postdoctoral Contract (Perfeccionamiento de Doctores) from the University of Granad

Impact of baseline platelet count in patients undergoing primary percutaneous coronary intervention in acute myocardial infarction (from the CADILLAC trial).

Despite the well-recognized role of platelets in the pathogenesis of acute myocardial infarction (AMI) and in the vascular responses to angioplasty, the relation between platelet count and outcomes after primary percutaneous coronary intervention (PCI) in AMI is unknown. We therefore determined the effect of baseline platelet count on clinical and angiographic outcomes of patients with AMI undergoing primary PCI. In the prospective, randomized CADILLAC trial, platelet count on admission was available in 2,021 of 2,082 patients (97.0%). Angiographic results and outcomes at 30 days and 1 year were stratified by quartiles of platelet count. Median platelet count was 231 x 10(9)/L (range 38 to 709). Primary PCI angiographic success rates were independent of platelet count. The 30-day incidence of target vessel thrombosis or reocclusion increased steadily across the higher quartiles of baseline platelet count (0.2%, 0.6%, 1.0%, and 2.0%, p = 0.027). At 1 year, patients with a baseline platelet count \u3eor=234 versus10(9)/L had higher rates of death or reinfarction (8.9% vs 4.5%,

Impact of ST-segment resolution after primary angioplasty on outcomes after myocardial infarction in elderly patients: an analysis from the CADILLAC trial.

BACKGROUND: Age is a strong independent predictor of outcomes after primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). Whether lower rates of reperfusion success contribute to the poor prognosis in elderly patients is unknown. METHODS: A formal ST-segment analysis substudy was performed in 695 patients undergoing primary PCI for AMI in the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial. Reperfusion success (determined by the magnitude of ST-segment elevation resolution [STR] after PCI) was evaluated in 4 age groups:(n = 163), \u3eor=50 to(n = 187), \u3eor=60 to(n = 194), and \u3eor=70 years (n = 151). RESULTS: There were no differences in the age groups for angiographic procedural success (\u3e91% in all, P =.6), postprocedural Thrombolysis in Myocardial Infarction grade 3 flow (\u3e94%, P =.8), and the proportions of patients with complete, partial, or absent STR (P \u3e.8). However, rates of 30-day mortality (0.6%, 1.1%, 3.6%, 6.0%, respectively) and major adverse cardiac events (MACE; 2.5%, 4.8%, 6.2% 9.3%, respectively) increased with age. Rates of mortality and MACE were also inversely related to the magnitude of STR. Absent STR (hazard ratio, 3.00; 95% CI, 1.37-6.58; P =.006) and age (hazard ratio, 1.34; 95% CI, 1.01-1.77; P =.04) were independent predictors of 30-day MACE by using multivariable modeling. CONCLUSIONS: Lack of effective myocardial reperfusion is not a contributory mechanism responsible for the high morbidity and mortality rates observed in elderly patients. Nevertheless, advanced age and absent STR are both independent predictors of adverse outcomes after primary PCI, emphasizing the importance of successful reperfusion in the elderly population

Outcome in elderly patients undergoing primary coronary intervention for acute myocardial infarction: results from the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial.

BACKGROUND: Biological age is a strong determinant of prognosis in patients with acute myocardial infarction (AMI). We sought to examine the impact of age after primary percutaneous coronary intervention in AMI and to determine whether routine coronary stent implantation and/or platelet glycoprotein IIb/IIIa inhibitors improve clinical outcomes in elderly patients after primary angioplasty. METHODS AND RESULTS: In the CADILLAC trial, 2082 patients with AMI were randomized to balloon angioplasty, angioplasty plus abciximab, stenting alone, or stenting plus abciximab. No patient was excluded on the basis of advanced age; patients ranging from 21 to 95 years of age were enrolled. One-year mortality increased for each decile of age, exponentially after 65 years of age (1.6% for patients \u3c55 \u3eyears, 2.1% for 55 to 65 years, 7.1% for 65 to 75 years, 11.1% for patients \u3e75 years; Por =65 years), 1-year rates of ischemic target revascularization (7.0% versus 17.6%; P CONCLUSIONS: Despite contemporary mechanical reperfusion strategies, mortality, major bleeding, and stroke rates remain high in elderly patients undergoing primary percutaneous coronary intervention, outcomes that are not affected by stents or glycoprotein IIb/IIIa inhibitors. By reducing restenosis, however, stent implantation improves clinical outcomes in elderly patients with AMI

Relation between leucocyte count, myonecrosis, myocardial perfusion, and outcomes following primary angioplasty.

We examined whether leukocytosis is a negative prognostic factor in patients who underwent primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI), and, if so, determined whether it is associated with impaired myocardial perfusion. Previous studies have identified leukocytosis as a predictor of mortality in AMI. Whether this association holds in patients how have undergone primary PCI using contemporary pharmacotherapy and correlates with impaired myocardial perfusion is unknown. Clinical outcomes and reperfusion success, using Thrombolysis In Myocardial Infarction (TIMI) flow and myocardial blush grades, were examined according to tertiles of baseline leukocyte count in 1,268 patients who underwent primary PCI for AMI in the CADILLAC trial. Patients with higher leukocyte count were younger and more likely to be current smokers. Preprocedure TIMI grade 0 flow was more frequent in patients with higher leukocyte counts, but postprocedural TIMI grade 3 flow rates were equally high (\u3e94%) in all 3 groups. Myocardial blush grade 2/3 was achieved at similar rates after PCI in patients with low, intermediate, and high baseline leukocyte counts (52.0% vs 51.5% vs 50.1%, p = 0.8). Higher baseline leukocyte counts were associated with greater myonecrosis (