Characteristics and outcome of patients with low-/intermediate-risk acute promyelocytic leukemia treated with arsenic trioxide - an international collaborative study

The aim of this study was to characterize a large series of 154 patients with acute promyelocytic leukemia (APL; median age, 53 years; range, 18-90 years) and evaluate real-life outcome after up-front treatment with arsenic trioxide (ATO) and alltrans retinoic acid (ATRA). All patients were included in the prospective NAPOLEON registry (NCT02192619) between 2013 and 2019. APL was de novo in 91% (n=140) and therapy-related in 9% (n=14); 13% (n=20) were older than 70 years. At diagnosis bleeding/hemorrhage was present in 38% and thrombosis in 3%. Complete remission was achieved in 152 patients (99%), whereas two patients (1%) experienced induction death within 18 days after start of therapy. With a median follow-up of 1.99 years (95%-CI, 1.61-2.30 years) 1-year and 2-years overall survival (OS) rates were 97% (95%-CI, 94-100%) and 95% (95%-CI, 91-99%), respectively. Age above 70 years was associated with a significantly shorter OS (P<0.001) as compared to younger patients. So far no relapses were observed. Six patients (4%) died in CR after in median 0.95 years after diagnosis (range, 0.18-2.38 years). Our data confirm the efficiency and durability of ATO/ATRA in the primary management of adult low-/ intermediate-risk APL patients in the real life setting, irrespective of age

Active behaviours produced by antidepressants and opioids in the mouse tail suspension test

Most classical preclinical tests to predict antidepressant activity were initially developed to detect compounds that influenced noradrenergic and/or serotonergic activity, in accordance with the monoaminergic hypothesis of depression. However, central opioid systems are also known to influence the pathophysiology of depression. While the tail suspension test (TST) is very sensitive to several types of antidepressant, the traditional form of scoring the TST does not distinguish between different modes of action. The present study was designed to compare the behavioural effects of classical noradrenergic and/or serotonergic antidepressants in the TST with those of opioids. We developed a sampling technique to differentiate between behaviours in the TST, namely, curling, swinging and immobility. Antidepressants that inhibit noradrenaline and/or serotonin re-uptake (imipramine, venlafaxine, duloxetine, desipramine and citalopram) decreased the immobility of mice, increasing their swinging but with no effect on their curling behaviour. No differences were observed between antidepressants that act on noradrenergic or serotoninergic transmission. While opioid compounds also decreased the immobility of the mice [morphine, codeine, levorphanol, (-)-methadone, (±)-tramadol and (+)-tramadol], they selectively increased curling behaviour. Blocking opioid receptors with naloxone prevented the antidepressant-like effect of codeine, and ο-opioid receptor knockout decreased normal curling behaviour and blocked (±)-tramadol-induced curling, further demonstrating the reliability and validity of this approach. These results show that at least two behaviourally distinct processes occur in the TST, highlighting the antidepressant-like effects of opioids evident in this test. Furthermore, our data suggest that swinging and curling behaviours are mediated by enhanced monoamine and opioid neurotransmission, respectively. © 2011 CINP.Peer Reviewe