Key Points• Chromosomal abnormalities predict outcome after relapse in BCP-ALL, and high-risk cytogenetics takes precedence over clinical risk factors. • Patients with mutations or deletions targeting TP53, NR3C1, BTG1, and NRAS were associated with clinical high risk and an inferior outcome.Somatic genetic abnormalities are initiators and drivers of disease and have proven clinical utility at initial diagnosis. However, the genetic landscape and its clinical utility at relapse are less well understood and have not been studied comprehensively. We analyzed cytogenetic data from 427 children with relapsed B-cell precursor ALL treated on the international trial, ALLR3. Also we screened 238 patients with a marrow relapse for selected copy number alterations (CNAs) and mutations. Cytogenetic risk groups were predictive of outcome postrelapse and survival rates at 5 years for patients with good, intermediate-, and high-risk cytogenetics were 68%, 47%, and 26%, respectively (P < .001). TP53 alterations and NR3C1/BTG1 deletions were associated with a higher risk of progression: hazard ratio 2.36 (95% confidence interval, 1.51-3.70, P < .001) and 2.15 (1.32-3.48, P 5 .002). NRAS mutations were associated with an increased risk of progression among standard-risk patients with high hyperdiploidy: 3.17 (1.15-8.71, P 5 .026). Patients classified clinically as standard and high risk had distinct genetic profiles. The outcome of clinical standard-risk patients with high-risk cytogenetics was equivalent to clinical high-risk patients. Screening patients at relapse for key genetic abnormalities will enable the integration of genetic and clinical risk factors to improve patient stratification and outcome. This study is registered at www.clinicaltrials.org as #ISCRTN45724312. (Blood. 2016;128(7):911-922)
As part of the management of an outbreak of meningococcal infection, 119 school contacts of an index case were swabbed for nasopharyngeal carriage. In a cohort study, risk factors for Neisseria meningitidis carriage were ascertained by means of a questionnaire, completed by 114 (96%) of those swabbed. Twenty five (21%) cultures were identified as "neisseria positive'; of which there were 18 (15%) Neisseria meningitidis isolates, 2 (2%) Neisseria lactamica isolates and 5 (4%) showed contaminants only. Two (2%) carriers were identified as harbouring the implicated outbreak strain. Single variable analysis identified six statistically significant risk factors for meningococcal carriage; increasing age, female sex, manual social class, personal smoking, regular attendance at a discotheque and rhinorrhoea. Multivariate analysis, using logistic regression modelling, found that of these six variables only age, sex and social class remained statistically significant when the other factors were controlled for. Nevertheless the role of smoking, social events and respiratory/viral infections in nasopharyngeal carriage, and other plausible mechanisms whereby age, sex and social class might exert their effect, could usefully be investigated further.
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