Association study of candidate DNA-repair gene variants and acute graft versus host disease in pediatric patients receiving allogeneic hematopoietic stem-cell transplantation

Acute Graft versus Host Disease (aGvHD) grades 2-4 occurs in 15-60% of pediatric patients undergoing allogeneic haematopoietic stem-cell transplantation (allo-HSCT). The collateral damage to normal tissue by conditioning regimens administered prior to allo-HSCT serve as an initial trigger for aGvHD. DNA-repair mechanisms may play an important role in mitigating this initial damage, and so the variants in corresponding DNA-repair protein-coding genes via affecting their quantity and/or function. We explored 51 variants within 17 DNA-repair genes for their association with aGvHD grades 2-4 in 60 pediatric patients. The cumulative incidence of aGvHD 2-4 was 12% (n = 7) in the exploratory cohort. MGMT rs10764881 (G>A) and EXO rs9350 (c.2270C>T) variants were associated with aGvHD 2-4 [Odds ratios = 14.8 (0 events out of 40 in rs10764881 GG group) and 11.5 (95% CI: 2.3-191.8), respectively, multiple testing corrected p A) remained significant (adjusted HR = 2.05 [95% CI: 1.06-3.94]; p = 0.03) in the presence of other clinical risk factors. Higher MGMT expression was seen in GG carriers for rs10764881 and was associated with higher IC50 of Busulfan in lymphoblastoid cells. MGMT rs10764881 carrier status could predict aGvHD occurrence in pediatric patients undergoing allo-HSCT.Transplantation and immunomodulatio

A National Long-Term Study of Neuroendocrine Tumors of the Appendix in Children: Are We Too Aggressive?

Pediatric neuroendocrine tumors (NETs) of the appendix are mostly detected incidentally after appendectomy for acute appendicitis. NET management is a matter of controversy. In this national, multicenter study, we aimed to establish guidelines based on our results and the literature. Medical records of children (0-16 years) with NET of the appendix, treated in Switzerland (1991-2012), were reviewed. Forty cases (28 girls) were analyzed. Median age at diagnosis was 12.7 years (interquartile range [IQR]: 4.0). Tumor size was 0.1-24 mm (median: 0.6, IQR: 0.6). Four patients (10%) underwent additional surgery because of either tumor size > 15 mm (1/4), extension to the mesoappendix (1/4), or incomplete resection (2/4). Three patients with a tumor of ≥ 20 mm had no additional surgery. No patient had lymph node metastases. All patients were in complete remission at the last follow-up (median: 3.0 years, IQR: 10.9). We conclude from this study and from an extensive review of the literature that two criteria may point to the need for additional surgery, i.e., the possibility of regional lymph node involvement: tumor size > 20 mm and incomplete surgical resection margins. Childhood NET of the appendix has an excellent prognosis

Prevalence and reasons for smoking in adolescent Swiss childhood cancer survivors.

Smoking harms health, particularly that of childhood cancer survivors, who face risk of pulmonary and cardiovascular diseases because of chemotherapy and radiotherapy to the chest. This nationwide study assessed smoking habits and reasons for smoking in adolescent survivors and healthy peers. As part of the Swiss Childhood Cancer Survivor Study, we sent a questionnaire to all Swiss resident survivors, who were aged 16-19 years. We compared smoking status and reasons for smoking between 511 survivors, 141 of their siblings, and 1,727 adolescents in a representative population-based study, the Tobacco Monitoring Switzerland (TMS). Current smoking was less prevalent in survivors (17%) and their siblings (17%) compared with TMS (32%). Survivors and TMS adolescents gave similar reasons for smoking. Stress control, smoking being a habit, and good taste were the reasons for smoking cited most often in both groups. Peer smoking was more important in survivors (49%) than in TMS (34%, P = 0.004). Most important reasons for not smoking in both groups were smoking being unhealthy and not wanting to be addicted. In Switzerland, survivors smoke as often as their siblings but less than the general population. Peer smoking was a more important reason for smoking in survivors than in the general population, suggesting that reducing smoking in peers could result in a reduction of smoking in survivors. Overall, reasons for smoking were very similar, thus interventions to reduce smoking in survivors could be the same as those used in the general population