Refractory acute myeloid leukemia (AML) includes AML includes failure of disease to respond to standard induction chemotherapy, relapse within 6 months after first CR, and 2 or more relapses. The outcome of these patients is usually very poor; only a small proportion can be rescued by allogenic hematopoietic stem-cell transplantation (allo-HSCT). The aim of this study was to evaluate the efficacy and feasibility of allo-HSCT in patients with refractory AML.
Patients and Methods
We retrospectively analyzed the clinical outcome of 91 patients who were diagnosed with treatment-refractory AML at Hacettepe University Hospital between January 2002 and June 2018. Patients' disease status included refractory AML, defined as failure to respond to standard induction chemotherapy and relapse within 6 months after first complete remission.
Results
The median follow-up was 12 months (range, 0.5-184 months) for the entire group. Kaplan-Meier estimates of the 3-year overall survival for patients who underwent allo-HSCT and patients who received only salvage chemotherapy were 67% and 12%, respectively. Additionally, the Kaplan-Meier estimates of 5-year overall survival for patients who underwent allo-HSCT and patients who received only salvage chemotherapy were 44% and 4%, respectively (P < .001). Complete remission was obtained in 25 patients (83.3%) who underwent allo-HSCT; however, the disease of only 3 patients (3.8%) exhibited complete response after salvage chemotherapy.
Conclusion
Allo-HSCT is still the best-known treatment option with curative potential in patients with treatment-refractory AML. Therefore, all efforts should be made in an attempt to find a suitable matched donor in order to perform allo-HSCT. 相似文献
Doxorubicin (DOX) is the most commonly used anticancer drug; however, it has limited use because prolonged administration may result in severe cardiotoxicity. Simvastatin (SIM), generally prescribed for hypercholesterolaemia, has also shown salubrious results in the monotherapy or combinational drug therapy of different cancers in various models. Nanoparticle drug delivery systems are a novel way of improving therapeutics and also improving the absorption and specificity of drugs towards tumour cells. In this study, we exploited this technology to increase drug specificity and minimize imminent adverse effects. In this study, the antitumour activity of the combination formulas of DOX and SIM, either loaded in water (DOX‐SIM‐Solution) or nanoemulsions (NEs) (DOX‐SIM‐NE), was evaluated in a Swiss albino mouse model of Ehrlich ascites carcinoma. The anticancer effect was assessed by quantifying the change in body weight, mean survival time, and percent increase in lifespan (%ILS), determining haematological and serum biochemical parameters (liver function test, kidney function test and lipid profile parameters) as well as studying the histopathological alterations in liver tissues. We observed a clear increase in %ILS of the DOX‐SIM‐Solution group (265.30) that was double the %ILS of the DOX‐SIM‐NE group (134.70). However, DOX‐SIM‐NE had a non‐toxic effect on the haematological parameters, whereas DOX‐SIM‐Solution increased the levels of haemoglobin and lymphocytes. Furthermore, the encapsulation of SIM and DOX into NEs improved the levels of all serum biochemical parameters compared to the DOX‐SIM‐Solution. A reduction in the side effects of DOX‐SIM‐NE on the liver was also established using light microscopy, which revealed that the morphologies of the hepatocytes of the mice were less affected by administration of the DOX‐SIM‐NE treatment than with the DOX‐SIM‐Solution treatment. The study showed that incorporating SIM into the DOX‐loaded‐NE formulation remarkably improved its efficiency and simultaneously reduced its adverse effects. 相似文献
Facial motion is a primary source of social information about other humans. Prior fMRI studies have identified regions of the superior temporal sulcus (STS) that respond specifically to perceived face movements (termed fSTS), but little is known about the nature of motion representations in these regions. Here we use fMRI and multivoxel pattern analysis to characterize the representational content of the fSTS. Participants viewed a set of specific eye and mouth movements, as well as combined eye and mouth movements. Our results demonstrate that fSTS response patterns contain information about face movements, including subtle distinctions between types of eye and mouth movements. These representations generalize across the actor performing the movement, and across small differences in visual position. Critically, patterns of response to combined movements could be well predicted by linear combinations of responses to individual eye and mouth movements, pointing to a parts‐based representation of complex face movements. These results indicate that the fSTS plays an intermediate role in the process of inferring social content from visually perceived face movements, containing a representation that is sufficiently abstract to generalize across low‐level visual details, but still tied to the kinematics of face part movements. 相似文献
BackgroundAlthough there are robust data about the pathophysiology and prognostic implications of left ventricular (LV) systolic dysfunction in patients with acquired heart disease, similar prognostic data about LV systolic dysfunction are sparse in the tetralogy of Fallot (TOF) population. The purpose of this study was to perform a meta-analysis of all studies that assessed the relationship between LV ejection fraction (LVEF) and cardiovascular adverse events (CAEs) defined as death, aborted sudden death, or sustained ventricular tachycardia.MethodsWe used random-effects models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsOf the 1,809 citations, 7 studies with 2,854 patients (age 28 ± 4 years) were included. During 5.6 ± 3.4 years' follow-up, there were 82 deaths, 17 aborted sudden cardiac deaths, and 56 sustained ventricular tachycardia events. Overall, CAEs occurred in 5.1% (144 patients). As a continuous variable, LVEF was a predictor of CAE (HR 1.29, 95% CI, 1.09-1.53, P = 0.001) per 5% decrease in LVEF. Similarly, LVEF < 40% was also a predictor of CAE (HR 3.22, 95% CI, 2.16-4.80, P < 0.001).ConclusionsLV systolic dysfunction was an independent predictor of CAE, and we observed a 30% increase in the risk of CAE for every 5% decrease in LVEF, and a 3-fold increase in the risk of CAE in patients with LVEF <40% compared with other patients. These findings underscore the importance of incorporating LV systolic function in clinical risk stratification of patients with TOF and the need to explore new treatment options to address this problem. 相似文献
Butyrylcholinesterase (BChE) is a serine esterase that plays a role in the detoxification of natural as well as synthetic ester-bond-containing compounds. Alterations in BChE activity are associated with a number of diseases. Cholinergic system abnormalities in particular are correlated with the formation of senile plaques in Alzheimer’s disease (AD), and administration of cholinesterase inhibitors is a common therapeutic approach used to treat AD.
Here, our aim was to study the interaction between BChE and fluoxetine.
Molecular docking simulations revealed that fluoxetine penetrated deep into the active-site gorge of BChE and that it was engaged in stabilizing noncovalent interactions with multiple subsites. In substrate kinetic studies, the Vm, Km, kcat and kcat/Km values were found to be 20.59?±?0.36?U mg?1 protein, 194?±?14?µM, 1.3?×?108?s?1 and 6.7?×?105?µM?1s?1, respectively. Based on inhibitory studies, fluoxetine appeared to inhibit BChE competitively, with an IC50 value of 104?µM and a Ki value of 36.3?±?4.7?µM.
Overall, both the low Ki value and the high number of BChE–fluoxetine interactions suggest that fluoxetine is a potent inhibitor of BChE, although in vivo mechanisms for the direct effects of BChE inhibition on various pathologies remain to be further investigated.