54 research outputs found
Bendamustine in association with rituximab for first-line treatment of diffuse large B-cell lymphoma in frail patients ineligible for R-CHOP/R-CHOP-like treatments
No full textR-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) has been considered the standard of care for diffuse large B cell lymphoma (DLBCL) patients, including in the elderlies, and represent the current standard treatment. Ineligibility for R-CHOP-like treatments seems to be associated with shorter survival. Recent studies have shown that bendamustine and rituximab is linked, in elderly patients affected by DLBCL. Here we report our experience with BR in 40 elderly frail patients affected by DLBCL ineligibles for R-CHOP. The OOR was 77.5%, with 22 complete responses and 9 partial responses statistical analysis showed no significant difference in overall survival (OS) between patients aged 80 years and older and patients younger than 80 years (6·4 vs. 10·2 months, respectively, P = 0·43). Complete responders were more likely patients with good performance status, (ECOG 0-1) 13 patients (60%), 9 patients (40%) were ECOG 2; of the 9 patients who achieved partial response, 7 patients had ECOG 0-1 and 2 patients had ECOG 2. Four patients had stable disease. Progression-free survival (PFS) median PFS was 13.5 months. These preliminary results showed that bendamustine and rituximab has been associated with high response rates, acceptable toxicity in frail DLBCL patients and high rate of OSS. In older patients with advanced IPI scores, no significant difference in OS were observed between patients aged 80 years and older and patients younger than 80 years. We conclude that bendamustine and rituximab seems to be a reasonable alternative for frail DLBCL patients
Personalized treatment strategies for elderly patients with myelodysplastic syndromes
No full textMyelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic disorders characterized by ineffective hematopoiesis and peripheral cytopenia, and their possible transformation into acute myeloid leukemia (AML). They typically affect the elderly but, when making treatment decisions, considering chronological age may be insufficient because it poorly correlates with patient frailty: the challenge is to select the optimal treatment in these patients by balancing efficacy and toxicity. Areas covered: This review discusses the rationale for and methods of personalizing the treatment of elderly MDS patients. Expert commentary: Decisions concerning treatment strategies for elderly MDS patients should be made after assessing their frailty on the basis of a geriatric assessment and an estimate of age-adjusted life expectancy. We suggest that all elderly MDS patients should undergo a timed up and go test (TUGT) as a preliminary means of identifying frail patients, and that all non-frail patients should then undergo a comprehensive geriatric assessment (CGA) in order to distinguish fit and pre-frail patients. Fit patients should receive standard dose treatment; pre-frail patients should receive individualized therapy; and frail patients should receive symptom-related therapy. A repeated CGA may be useful to evaluate the hematological, cognitive and socio-relational effects of MDS treatment
Interaction of C1 inhibitor with thrombin on the endothelial surface
No full textThrombin, the central bioregulatory enzyme of haemostasis, also has a potent vasopermeability effect on the surface of endothelial cells, and has therefore been considered a major link between the activation of the coagulation pathway and inflammation. C1 inhibitor inhibits thrombin with a low second-order rate constant that can be increased by heparin. The aim of this study was to investigate whether the C1 inhibitor-induced inhibition of thrombin is potentiated on the endothelial surface. The interaction of C1 inhibitor and thrombin was evaluated in an in-vitro system of human umbilical vein endothelial cells (HUVECs) to which purified C1 inhibitor and thrombin have been added. The role of heparins and selectins has been tested by adding heparinase and Mab to selectins. Kinetic analysis under pseudo-first-order conditions showed that the inhibitory effect of C1 inhibitor on thrombin is greater on the surface of endothelial cells. After incubating nanomolar concentrations of thrombin and micromolar concentrations of C1 inhibitor in a purified system, thrombin activity remained significant, but was almost totally suppressed in the presence of HUVECs. The abolition of such suppression by heparinase and Mab to selectins supports the involvement of heparin and selectins in C1 inhibitor– thrombin interaction. Furthermore, the second-order rate constant was 25 +/- 3 /s per mol/l in our purified system, but increased to 100 +/- 9 /s per mol/l in the presence of HUVECs. Our results indicate that C1 inhibitor can inhibit thrombin activity on vascular endothelium via binding to selectins and potentiation by heparins. This may contribute to the modulation of thrombin activity on vasopermeability and on coagulation especially when the major natural anticoagulant pathways are impaired
First-line treatment with bendamustine and rituximab, in patients with intermediate-/high-risk splenic marginal zone lymphomas
No full textSplenic marginal zone lymphomas (SMZLs) are rare indolent B cell neoplasms that affect the spleen, bone marrow, and blood. Although they have an indolent course in the majority of patients, who have a median survival of 8-10 years, ∼ 30% may experience a worse outcome. The prognostic criteria of progression are lymph node and extra-nodal involvement, high lymphocyte counts, anaemia, and thrombocytopenia. The treatment of SMZLs include a "wait and watch strategy", splenectomy, and alkylating agents ± rituximab. We here describe data relating to 70 patients with intermediate-/high-risk SMZLs, who received rituximab/bendamustine as first-line treatment for a median of 60 days (range 1-75) after diagnosis. Sixty patients (86%) achieved a complete response (CR), and seven (10%) a partial response (PR). Three patients (4.3%) experienced disease progression (PD). The median duration of remission was 18 months. Side effects were generally mild. Our findings suggest that rituximab/bendamustine is a feasible treatment option in patients with intermediate-/high-risk SMZLs
Does Outcome/Survival of Patients With Myelodysplastic Syndromes Should Be Predicted by Reduced Levels of ADAMTS-13? Results From a Pilot Study
No full textIntroduction: Von Willebrand factor (vWF) cleaving protease ADAMTS-13 has a key role for maintaining normal size of vWF. A deficiency or dysfunction of vWF cleaving protease is associated with ultra large vWF multimers and thrombotic microangiopathy. Patients with cancers have reduced levels of vWF cleaving protease. In this pilot study, we have evaluated whether or not deficiencies of ADAMTS-13 were present in myelodysplastic syndromes (MDS). Moreover, we assessed if a reduction in basal levels of ADAMTS-13 may play a role in the prognosis of MDS.
Patients and methods: We measured and compared the levels of vWF cleaving protease ADAMTS-13 in 100 patients with MDS and 35 healthy controls. Patients were divided into 2 groups according to the International Prognostic Scoring System: group I consisting of 44 patients with low-risk MDS and group II of 56 patients with high-risk MDS. Patients with high-risk and low-risk MDS presented significantly lower levels of ADAMTS-13 than controls (P < .001 and P = .0177, respectively). High-risk patients had significantly lower levels of ADAMTS-13 when compared with the low-risk group (P < .001).
Results: We found that reduced levels of ADAMTS-13 have a relationship with overall survival (P < .001). Statistical analysis showed that ADAMTS-13 correlates with cytogenetics (P < .001) and a tendency of slight correlation with platelet count and basal levels of ADAMTS-13 (R, 0.35; P value, 0.001). Moreover, we found that levels of ADAMTS-13 have correlation with response to treatment (P < .001).
Conclusions: ADAMTS-13 in MDS might represent a surrogate marker of prognosis, response to therapy, or disease progression. Further studies are needed
The impact of an aging population on the diagnosis of pulmonary embolism: comparison of young and elderly patients
No full textProthrombotic and inflammatory markers in elderly patients with non-alcoholic hepatic liver disease before and after weight loss: A pilot study
No full textBackground: Non-alcoholic fatty liver disease (NAFLD) is a pathological condition, ranging from fatty liver to chronic steatohepatitis (NASH), liver cirrhosis, and eventually to hepatocellular carcinoma. Recent findings suggest that patients with NAFLD have an increased risk of cardiovascular events and thromboembolism, which is independent of metabolic diseases that are frequently associated with NAFLD, such as diabetes, hyperlipidemia, and obesity. Methods: We evaluated 30 NAFLD patients, before and after weight loss. Plasma levels of C-reactive protein (CRP), fibrinogen, plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (VWF), homocysteine, coagulation protein S, Thrombin activable fibrinolysis inhibitor (TAFI), and factor VII (FVII) were assessed to evaluate whether they should be responsible of the prothrombotic state of NAFLD after weight loss. Results: At baseline, patients affected by NAFLD had a significantly higher levels of CRP, fibrinogen, PAI-1, VWF antigen, and FVII levels. After weight reduction, we observed a significant drop of inflammatory and prothrombotic markers, as well as glucometabolic, lipid profile. Conclusion: These findings provide evidence for a link between NAFLD/NASH and thromboembolism. The association seems to be linked with primitive thrombotic state and hypercoagulation due to increased levels of coagulation factors and reduced levels of PAI-1. This hypercoagulation state might explain increased levels of thrombosis and splanchnic thrombosis observed in NASH correlated cirrhosis
Caregiver burden as a short-term predictor of weight loss in older outpatients suffering from mild to moderate Alzheimer’s disease : a three months follow-up study
No full textObjective : To determine if caregiver burden (CB) can be an independent predictive factor of weight loss at three months in older outpatients suffering from mild to moderate Alzheimer's disease (AD) and living at home.
Method : Prospective cohort study involving 105 subjects aged 70 years or more, affected by mild to moderate AD and living at home with the assistance of at least one informal caregiver, who consecutively underwent a multidimensional geriatric assessment. Body weight was re-evaluated at a three month follow-up, from December 2008 to April 2009. Those who experienced a weight loss greater than 3% of the baseline weight constituted the 'weight loss' group. Results : Out of the 97 older participants attending follow-up, 22 (23%) had experienced a weight loss > 3%. At a multivariate logistic regression analysis, a greater CB at baseline, defined by a score of the caregiver burden inventory scale in the highest tertile (i.e. 36+ out of 96), turned out to predict weight loss at three months (odds ratio (OR) 13.93, 95% confidence interval (CI) 1.91-101.33, p = 0.009), independently of other factors associated with the 'weight loss' group such as age, functional dependence and the risk of malnutrition estimated by means of the Mini Nutritional Assessment Short Form (MNA-SF). Conclusion : For older outpatients affected by mild to moderate AD and living at home, CB constitutes a risk factor for weight loss even in the short-term, independently of other factors such as the risk of malnutrition assessed by means of the MNA-S
Risk-tailored treatment of splenic marginal zone lymphoma
No full textSplenic marginal zone lymphoma (SMZL) is a rare lymphoproliferative disease involving B-cells and affecting elderly patients. SMZL plague peripheral blood and bone marrow, spleen. Lymph nodes are generally spared. SMZL is due to a protracted antigen stimulation of B lymphocytes and of microenvironment leading B-cell to polyclonal and then oligoclonal/monoclonal growth, promoting lymphoproliferation. Integration of the NOTCH2 and NFk-B signaling has been recently identified as the primary mechanism of neoplastic proliferation in SMZL. In total 20% of cases carry mutations in NOTCH2. Although SMZL has an indolent course, progression to diffuse large B-cell lymphoma occurs in about 10-15% of patients. Establishing the prognosis is a key step in disease management, depending on both individual risk and patients' health status. This review discusses tailored treatment of SMZL patients. Progression risk factors include nodal and extra-nodal involvement, peripheral lymphocytosis, anemia and thrombocytopenia. Patients with two or more score points have a median survival of <5 years. Watch and wait strategy is appropriate in low-risk and asymptomatic patients, whereas treatment of symptomatic patients ranges from splenectomy to rituximab monotherapy or associated with chemotherapy
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