Acute myeloid leukemia: negative prognostic impact of early blast persistence can be in part overcome by a later remission prior to post-induction therapy

In acute myeloid leukemia, there is an ongoing debate on the prognostic value of the early bone marrow assessment in patients receiving intensive therapy. In this retrospective study, we analyzed the prognostic impact of the early response in 1,008 patients with newly diagnosed acute myeloid leukemia, who were treated at our institution with intensive chemotherapy followed by consolidation chemotherapy and/or allogeneic hematopoietic stem cell transplantation (HSCT). We found that early blast persistence has an independent negative prognostic impact on overall survival, event-free survival and relapse-free survival. This negative prognostic impact may only be overcome in patients showing at least a partial remission at the early bone marrow assessment and who subsequently achieve blast clearance by additional induction chemotherapy prior to consolidation therapy with allogeneic HSCT. In accordance, we propose that the time slope of remission is an additional leukemia-related dynamic parameter that reflects chemosensitivity and thus may inform post-induction therapy decision-making. In addition to patient-related factors, European LeukemiaNet risk group, measurable residual disease monitoring and donor availability, this may particularly apply to European LeukemiaNet intermediate-risk patients, for whom a decision between consolidation chemotherapy and allogeneic HSCT remains challenging in many cases.     

Randomized Phase II Study of Two Doses of Pixantrone in Patients with Metastatic Breast Cancer (NCCTG N1031, Alliance)

BackgroundAnthracycline use in metastatic breast cancer (MBC) is hindered by cumulative exposure limits and risk of cardiotoxicity. Pixantrone, a novel aza-anthracenedione with structural similarities to mitoxantrone and anthracyclines, is theorized to exhibit less cardiotoxicity, mainly due to lack of iron binding. We conducted a randomized phase II study to evaluate the efficacy and safety of 2 dosing schedules of pixantrone in patients with refractory HER2-negative MBC.MethodsIntravenous pixantrone was administered at 180 mg/m² every 3 weeks (group A) versus 85 mg/m² on days 1, 8, and 15 of a 28-day cycle (group B). Primary endpoint was objective response rate (ORR) and secondary endpoints included progression-free survival (PFS), median 6-month PFS, overall survival (OS), safety, quality of life, and serial assessment of circulating tumor cells. A 20% ORR was targeted as sufficient for further testing of pixantrone in this patient population.ResultsForty-five patients were evaluable, with 2 confirmed partial responses in group A and 1 in group B. The trial was terminated due to insufficient activity. Overall median PFS and OS were 2.8 (95% confidence interval [CI]: 2.0-4.1) and 16.8 (95% CI: 8.9-21.6) months, respectively. Notable overall grade 3-4 adverse events were the following: neutrophil count decrease (62%), fatigue (16%), and decrease in ejection fraction (EF) (4%).ConclusionPixantrone has insufficient activity in the second- and third-line MBC setting. It appears, however, to have limited cardiotoxicity. (ClinicalTrials.gov ID: {"type":"clinical-trial","attrs":{"text":"NCT01086605","term_id":"NCT01086605"}}NCT01086605).     

Prevention of postoperative intestinal adhesions with combined promethazine and dexamethasone therapy: experimental and clinical studies.

This study, combining experimental and clinical data, attempted to develop methods to prevent formation of adhesions in the highly susceptible infant undergoing abdominal surgery and to inhibit reformation of adhesions after surgical division of those which had appeared after some previous operation. Rats were treated with a combination of dexamethasone (Decadron) and promethazine (Phenergan). This series showed that the inflamma tory phase that follows trauma to intestinal serosa can be minimized and the organization of inflammatory exudate into fibrous adhesions can be delayed with this combination treatment (antihistamine plus adrenal cortex hormones). An addendum notes that so far 81 patients have been treated with the drug combination, and the results are characterized as very satisfactory, with no complications related to treatment. 2 points are emphasized: 1) since adhesion formation begins within minutes of peritoneal trauma, prevention requires a high level of drug saturation at the time of injury; and 2) large doses of drugs are required for maximum benefit. Experimentally, this study used 1 mg/kg of each drug, intramuscularly, 6-3 hours preoperatively, with dose repetetion via intraperitoneal saline as the abdomen is being closed for 2-36 hours postoperatively.     

Vécu subjectif de la maladie et de la guérison chez 13 adolescents et jeunes adultes traités pour une hémopathie maligne dans l’enfance

The authors report the results of a study conducted in 2010, which consisted meeting, through a semi-structured interview, 13 adolescents or young adults medically cured of childhood haematological malignancies, treated in the department of haematology at the Children’s Hospital of Nancy. The objective is to explore the experience of illness and treatment, especially the experience of recovery. Some of them present significant distress in various subjects. Thus, body image and self-esteem are often altered among these young patients. Concerns about possible infertility or severe sexual dysfunction are found. Ambivalence about their future parenting emerges from their speech. These elements are obstacles to the recovery process. A follow-up psychological consultation could be provided in a systematic way by a professional trained in these specific problems.     

A Randomized,Controlled Trial to Investigate the Effect of Ciclesonide and Beclomethasone Dipropionate on Eye Lens Opacity

Background. Inhaled corticosteroids (ICS) are recommended first-line therapy for the treatment of persistent asthma. However, reports from observational studies have suggested that the use of ICS may be associated with systemic adverse events, such as glaucoma and cataract (opacity of the lens) formation. Objective. To compare two ICS over 1 year regarding the formation/progression of lenticular opacities in patients with asthma. Methods. Adults (≥ 18 years of age) with moderate-to-severe asthma were randomized to ciclesonide 640 μ g/day (n = 785) or beclomethasone dipropionate 640 μ g/day (n = 783) in a multinational, double-blind, active-controlled, parallel-group study. The primary endpoint was the occurrence of a positive Class I grading shift (increase [worsening] in Lens Opacities Classification System [LOCS] III score of ≥ 0.5 for nuclear opalescence, ≥ 0.8 for cortical opacification, or ≥ 0.5 for posterior subcapsular opacification, or cataract surgery) in either eye at any visit over the 12-month, double-blind treatment period. Results. Mean changes (± standard error) in nuclear opalescence and cortical and posterior subcapsular opacification were small and similar between groups (ciclesonide 640 μ g/day: 0.10 ± 0.02, 0.07 ± 0.02 and 0.04 ± 0.01, respectively; beclomethasone dipropionate 640 μ g/day: 0.11 ± 0.02, 0.09 ± 0.02 and 0.03 ± 0.01, respectively). Class I shifts were observed in 34.3% versus 36.8% of ciclesonide-treated and beclomethasone dipropionate-treated patients, respectively. Ciclesonide 640 μ g/day was non-inferior to beclomethasone dipropionate 640 μ g/day regarding Class I shifts (risk ratio of ciclesonide to beclomethasone dipropionate, 0.940 [95% confidence interval, 0.820–1.077]); the 95% confidence interval upper bound was lower than the pre-specified non-inferiority bound of 1.333 (p < 0.0001), thereby excluding the possibility of higher risk ratio values. Conclusions. Mean changes in LOCS III scores were very small in both groups. Treatment with ciclesonide 640 μ g/day or beclomethasone dipropionate 640 μ g/day for 1 year has a minimal impact on lenticular opacities development and/or progression.     

γ-去氢骆驼蓬碱等咔啉类生物碱的辐射防护作用

γ- Harmine(Ⅰ),’harmine(Ⅱ )and harmaline(Ⅲ )were isolated from PeganumHarmala L.( Zygophylaceae).Tests were conducted with mice to detect whether γ- harmine( a newcompound), harmine,harmof(Ⅳ)and harmalol(Ⅴ) are effective radioprotective compounds againstγ-ray irradiation, Intraperitoneal injection of the hydrochlorides of the four alkaloids 50～80mg·kg^-1×1 in NIH male mice 30～45 minutes before 8.6～9. 7 Gy whole body ⁶⁰Co irradiationsignificantly increased the survival effects(1. 33～2. 61)and 30-day survivai rate in comparison withcontrol mice.The results indicatethat γ- harmine exhibited relatively good radioprotective effect.γ-harmine is the first alkaloid isolated from a plant having ptotective effects against whole-body lethal irradiation in mice.