Thiopurine Enhanced ALL Maintenance (TEAM) : study protocol for a randomized study to evaluate the improvement in disease-free survival by adding very low dose 6-thioguanine to 6-mercaptopurine/methotrexate-based maintenance therapy in pediatric and adult patients (0-45 years) with newly diagnosed B-cell precursor or T-cell acute lymphoblastic leukemia treated according to the intermediate risk-high group of the ALLTogether1 protocol

Background: A critical challenge in current acute lymphoblastic leukemia (ALL) therapy is treatment intensification in order to reduce the relapse rate in the subset of patients at the highest risk of relapse. The year-long maintenance phase is essential in relapse prevention. The Thiopurine Enhanced ALL Maintenance (TEAM) trial investigates a novel strategy for ALL maintenance. Methods: TEAM is a randomized phase 3 sub-protocol to the ALLTogether1 trial, which includes patients 0-45 years of age with newly diagnosed B-cell precursor or T-cell ALL, and stratified to the intermediate risk-high (IR-high) group, in 13 European countries. In the TEAM trial, the traditional methotrexate (MTX)/6-mercaptopurine (6MP) maintenance backbone (control arm) is supplemented with low dose (2.5-12.5 mg/m(2)/day) oral 6-thioguanine (6TG) (experimental arm), while the starting dose of 6MP is reduced from 75 to 50 mg/m(2)/day. A total of 778 patients will be included in TEAM during similar to 5 years. The study will close when the last included patient has been followed for 5 years from the end of induction therapy. The primary objective of the study is to significantly improve the disease-free survival (DFS) of IR-high ALL patients by adding 6TG to 6MP/MTX-based maintenance therapy. TEAM has 80% power to detect a 7% increase in 5-year DFS through a 50% reduction in relapse rate. DFS will be evaluated by intention-to-treat analysis. In addition to reducing relapse,TEAM may also reduce hepatotoxicity and hypoglycemia caused by high levels of methylated 6MP metabolites. Methotrexate/6MP metabolites will be monitored and low levels will be reported back to clinicians to identify potentially non-adherent patients. Discussion: TEAM provides a novel strategy for maintenance therapy in ALL with the potential of improving DFS through reducing relapse rate. Potential risk factors that have been considered include hepatic sinusoidal obstruction syndrome/nodular regenerative hyperplasia, second cancer, infection, and osteonecrosis. Metabolite monitoring can potentially increase treatment adherence in both treatment arms.Peer reviewe

Optimization of the Sustainable Production of Resistant Starch in Rice Bran and Evaluation of Its Physicochemical and Technological Properties

In this study, the optimization of ultrasound (US) (850 kHz, 120 W) processing parameters (temperature, time, and power) for the enhanced production of resistant starch (RS) in rice bran (RB) matrixes was performed. The effect of US cavitation at different temperatures on the morphology, physicochemical properties, and mechanical performance of RS was evaluated. Ultrasonication at 40–70 °C temperatures affected the chemical structure, reduced the crystallinity of RS from 23.85% to between 18.37 and 4.43%, and increased the mechanical and thermal stability of RS pastes, indicating a higher tendency to retrograde. US treatment significantly (p < 0.05) improved the oil (OAC) and water (WAC) absorption capacities, swelling power (SP), solubility (WS), and reduced the least-gelation concentration (LGC). The mathematical evaluation of the data indicated a significant effect (p < 0.05) of the US parameters on the production of RS. The largest increment of RS (13.46 g/100 g dw) was achieved with US cavitation at 1.8 W/cm2 power, 40.2 °C temperature, and 18 min of processing time. The developed method and technology bring low-temperature US processing of rice milling waste to create a new sustainable food system based on modified rice bran biopolymers