Overall, these results provide strong evidence that EBV status is an etiologically important classification of cHL and also suggest that some components of the pathological process are common to both EBV-positive and EBV-negative patients.
SummaryGenotyping of TPMT prior to 6-mercaptopurine (6-MP) administration in acute lymphoblastic leukaemia (ALL) patients has been integrated into clinical practice in some populations of European ancestry. However, the comparable rates of 6-MP myelotoxicity, but rarity of TPMT variants, in Asians suggest that major determinants have yet to be discovered in this population. We genotyped 92 Japanese paediatric ALL patients for NUDT15 rs116855232, a 6-MP toxicity-related locus discovered in Asians. Logistic regression and survival analysis were used to evaluate its association with leucopenia, hepatotoxicity, 6-MP dose reduction, therapy interruption and event-free survival. The allele frequency of rs116855232 was 0Á16, and leucopenia was more common in carriers of the T allele (odds ratio, 7Á20; 95% confidence interval, 2Á49-20Á80; P = 2Á7 9 10
À4). As leucopenia results in 6-MP dose reduction, we observed average doses during maintenance therapy of 40Á7, 29Á3 and 8Á8 mg/m 2 for patients with CC, CT and TT genotypes, respectively (P < 0Á001). Hepatotoxicity was observed only in CC genotype patients. Event-free survival did not significantly differ by NUDT15 genotype. rs116855232 is an important determinant of 6-MP myelotoxicity in Japanese children with ALL and may represent the most robust toxicity-related locus in Asians to date. Considerations for clinical application may be warranted.
The associations between childhood acute lymphoblastic leukemia (ALL) and several proxies of early stimulation of the immune system, that is, day-care center attendance, birth order, maternally reported common infections in infancy, and breastfeeding, were investigated by using data from 11 case-control studies participating in the Childhood Leukemia International Consortium (enrollment period: 1980-2010). The sample included 7,399 ALL cases and 11,181 controls aged 2-14 years. The data were collected by questionnaires administered to the parents. Pooled odds ratios and 95% confidence intervals were estimated by unconditional logistic regression adjusted for age, sex, study, maternal education, and maternal age. Day-care center attendance in the first year of life was associated with a reduced risk of ALL (odds ratio = 0.77, 95% confidence interval: 0.71, 0.84), with a marked inverse trend with earlier age at start (P < 0.0001). An inverse association was also observed with breastfeeding duration of 6 months or more (odds ratio = 0.86, 95% confidence interval: 0.79, 0.94). No significant relationship with a history of common infections in infancy was observed even though the odds ratio was less than 1 for more than 3 infections. The findings of this large pooled analysis reinforce the hypothesis that day-care center attendance in infancy and prolonged breastfeeding are associated with a decreased risk of ALL.
Background Childhood acute lymphoblastic leukaemia (ALL) may be the result of a rare response to common infection(s) acquired by personal contact with infected individuals. A meta-analysis was conducted to examine the relationship between day-care attendance and risk of childhood ALL, specifically to address whether early-life exposure to infection is protective against ALL.Methods Searches of the PubMed database and bibliographies of publications on childhood leukaemia and infections were conducted. Observational studies of any size or location and published in English resulted in the inclusion of 14 case–control studies.Results The combined odds ratio (OR) based on the random effects model indicated that day-care attendance is associated with a reduced risk of ALL [OR = 0.76, 95% confidence interval (CI): 0.67, 0.87]. In subgroup analyses evaluating the influence of timing of exposure, a similarly reduced effect was observed for both day-care attendance occurring early in life (≤2 years of age) (OR = 0.79, 95% CI: 0.65, 0.95) and day-care attendance with unspecified timing (anytime prior to diagnosis) (OR = 0.81, 95% CI: 0.70, 0.94). Similar findings were observed with seven studies in which common ALL were analysed separately. The reduced risk estimates persisted in sensitivity analyses that examined the sources of study heterogeneity.Conclusions This analysis provides strong support for an association between exposure to common infections in early childhood and a reduced risk of ALL. Implications of a ‘hygiene’-related aetiology suggest that some form of prophylactic intervention in infancy may be possible.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.