Evans syndrome (ES) is a rare severe autoimmune disorder characterized by the combination of autoimmune hemolytic anemia and immune thrombocytopenia. In most cases, the underlying cause is unknown. We sought to identify genetic defects in pediatric ES (pES), based on a hypothesis of strong genetic determinism. In a national, prospective cohort of 203 patients with early-onset ES (median [range] age at last follow-up: 16.3 years ([1.2-41.0 years]) initiated in 2004, 80 nonselected consecutive individuals underwent genetic testing. The clinical data were analyzed as a function of the genetic findings. Fifty-two patients (65%) received a genetic diagnosis (the M+ group): 49 carried germline mutations and 3 carried somatic variants. Thirty-two (40%) had pathogenic mutations in 1 of 9 genes known to be involved in primary immunodeficiencies (TNFRSF6, CTLA4, STAT3, PIK3CD, CBL, ADAR1, LRBA, RAG1, and KRAS), whereas 20 patients (25%) carried probable pathogenic variants in 16 genes that had not previously been reported in the context of autoimmune disease. Lastly, no genetic abnormalities were found in the remaining 28 patients (35%, the M− group). The M+ group displayed more severe disease than the M− group, with a greater frequency of additional immunopathologic manifestations and a greater median number of lines of treatment. Six patients (all from the M+ group) died during the study. In conclusion, pES was potentially genetically determined in at least 65% of cases. Systematic, wide-ranging genetic screening should be offered in pES; the genetic findings have prognostic significance and may guide the choice of a targeted treatment.

In children, lymphoblastic lymphomas represent 30% of Non-Hodgkin lymphomas (NHL), and approximately 15% are precursor B-cell lymphomas (PBLL). Our study evaluated their main clinical characteristics, evolution, and prognosis in three trials. From 1989 to 2008, 53 children with PBLL (median age 7·75 years) were included in three protocols: Malignant Lymphoma Therapy (LMT) 96, European Organization for Research and Treatment of Cancer (EORTC) 58881, and EORTC 58951 using Berlin-Frankfürt-Münster-derived acute lymphoblastic leukaemia (ALL) therapy. There were 10 stage I disease, 9 stage II, 9 stage III and 25 stage IV. Clinical presentation was heterogeneous with a majority of bone lesions and cutaneous or subcutaneous manifestations. At diagnosis 23 patients had bone marrow involvement, and only three had central nervous system involvement. The median follow-up was 74 months. At last follow-up, 45 patients were in continuous complete remission, whereas eight had progressed or had relapsed (7 Stages IV and 1 Stage III) and died. Two patients had a secondary neoplasia, and are still alive. Disease stage was a major prognostic factor, with better overall survival (OS) and event-free survival (EFS) (P < 0·05) rates observed in patients with Stage I to III as compared to those with Stage IV. Treatment with protocols derived from ALL therapy are efficient with an 82% EFS and an 85% OS at 5 years

Every year, acute lymphoblastic leukaemia (ALL) affects about 400 children aged o15 years in France,

The study findings support the hypothesis that maternal folic acid supplementation may reduce the risk of childhood AL. The findings also suggest that the genotype homozygous for any of the MTHFR variants and carrying both MTRR variants could be a risk factor for AL.

Key Points Nilotinib demonstrated efficacy and a manageable safety profile in pediatric patients with newly diagnosed and pretreated Ph+ CML-CP.

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The results suggest that subfertility in itself and ovulation induction may be associated with ALL, and support a positive association with congenital malformations. The links with the various types of fertility drugs and the underlying causes of infertility need to be investigated further.

Background:Factors related to early stimulation of the immune system (breastfeeding, proxies for exposure to infectious agents, normal delivery, and exposure to animals in early life) have been suggested to decrease the risk of childhood acute lymphoblastic leukaemia (ALL).Methods:The national registry-based case–control study, ESTELLE, was carried out in France in 2010–2011. Population controls were frequency matched with cases on age and gender. The participation rates were 93% for cases and 86% for controls. Data were obtained from structured telephone questionnaires administered to mothers. Odds ratios (OR) were estimated using unconditional regression models adjusted for age, gender, and potential confounders.Results:In all, 617 ALL and 1225 controls aged ⩾1 year were included. Inverse associations between ALL and early common infections (OR=0.8, 95% confidence interval (CI): 0.6, 1.0), non-first born (⩾3 vs 1; OR=0.7, 95% CI: 0.5, 1.0), attendance of a day-care centre before age 1 year (OR=0.7, 95% CI: 0.5, 1.0), breastfeeding (OR=0.8, 95% CI: 0.7, 1.0), and regular contact with pets (OR=0.8, 95% CI: 0.7, 1.0) in infancy were observed.Conclusions:The results support the hypothesis that conditions promoting the maturation of the immune system in infancy have a protective role with respect to ALL.