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BackgroundA 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.MethodsTEAM 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/m2/day) oral 6-thioguanine (6TG) (experimental arm), while the starting dose of 6MP is reduced from 75 to 50 mg/m2/day. A total of 778 patients will be included in TEAM during ~ 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.DiscussionTEAM 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.Trial registrationEudraCT, 2018–001795-38. Registered 2020-05-15,Clinicaltrials.gov,NCT04307576. Registered 2020-03-13,https://clinicaltrials.gov/ct2/show/NCT04307576

In 2016, marketers spent $13.7 billion globally on online consumer research.[1][1] This investment reflected a compound annual growth rate of 6 percent since 2011. At the same time, consumers increasingly were taking online surveys using their smartphones. During the five-year period through 2016

Recent court cases in the United Kingdom have drawn attention to recurrence of sudden infant death syndrome (SIDS) within a family, with estimates of its frequency ranging from 1 in 73000000 (the figure for which Meadow was censured by the General Medical Council [GMC]) to 1 in 200 (the figure now favored by the United Kingdom media). In an attempt to arrive at a more balanced estimate, we reexamined the 8 published studies of recurrent SIDS conducted in Australia, Norway, the United Kingdom, and the United States between 1965 and 1999.1 We assessed the studies by using 3 criteria: completeness of ascertainment; accuracy of diagnosis; and matching of controls. Ascertainment was usually imperfect but not critical. Diagnosis cannot always be certain for an entity defined by exclusion. In the 40 years since the term SIDS was introduced, a number of familial disorders that may cause unexpected death in infancy, notably defects of fat metabolism, have been … Address correspondence to Christopher Bacon, FRCPCH, Glebe House, Danby Wiske, Northallerton, North Yorkshire DL7 OLY, UK. E-mail: chrisandheatherbacon{at}ukonline.co.uk