Key Points: Identification of SRP54 mutations in congenital neutropenia. SRP54 mutations induce ER stress and autophagy associated with apoptosis.

Although survival from childhood cancer has increased, little is known on the long-term impact of treatment late effects on occupational attainment or work ability. A total of 3512 five-year survivors treated before the age of 19 years in 10 French cancer centres between 1948 and 2000 were identified. Educational level, employment status and occupational class of survivors were assessed by a self-reported questionnaire. These outcome measures were compared with sex–age rates recorded in the French population, using indirect standardisation. Paternal occupational class was also considered to control for the role of survivors’ socioeconomic background on their achievement. Multivariable analyses were conducted to explore clinical characteristics associated with the outcomes. A total of 2406 survivors responded to the questionnaire and survivors aged below 25 years were included in the current analysis. Compared with national statistics adjusted on age and sex, male survivors were more likely to be college graduates (39.2% vs 30.9% expected; P<0.001). This higher achievement was not observed either for leukaemia or central nervous system (CNS) tumour survivors. Health-related unemployment was higher for survivors of CNS tumour (28.1% vs 4.3%; P<0.001) but not for survivors of other diagnoses. Survivors of non-CNS childhood cancer had a similar or a higher occupational class than expected. Survivors treated for CNS tumour or leukaemia, especially when treatment included cranial irradiation, might need support throughout their lifespan.

The purpose of this study was to identify risk factors for hypothyroidism after bone marrow transplantation (BMT) for high-risk or relapsed acute lymphoblastic leukaemia (ALL) in children. In all, 388 children with acute lymphoblastic leukaemia underwent allogeneic bone marrow transplantation between 1984 and 1994. Overall 5-year survival was 54.6%. Thyroid function was assessed in the 153 patients with more than 5 years of follow-up. In total, 16 patients developed uncompensated hypothyroidism (UH) and 46 compensated hypothyroidism (CH) a median of 2.9 and 2.7 years, respectively, after BMT. Thyroid dysfunction-free survival rates were 73.2% after 5 years and 59.2% after 10 years. Three factors were significantly associated with the onset of hypothyroidism, namely age, bone marrow transplantation in second remission, and single-dose total body irradiation (TBI). Ultrasonography of the thyroid showed nodules in 10 of 35 patients. The median time from BMT to nodule detection was 7.8 years. Cytology (n=5) and surgery (n=4) showed no evidence of thyroid cancer. Four of the 14 patients who received cytoreduction without TBI but with busulphan and cyclophosphamide developed UH (n=2) or CH (n=2). We concluded that children who undergo BMT for ALL are at a high risk of subsequent thyroid dysfunction.

Purpose: Survival of children and adolescents and young adults (AYAs) treated for cancer has increased with improved treatments. However, there is still an increased risk of second primary cancer (SPC) in the long term compared with the same-age population, especially related to treatments. The follow-up of this population and the prevention of SPC are important issues. Therefore, this study aimed to review the available literature on cancer risk factors (lifestyle and occupational exposures) in children and AYAs previously treated for cancer in order to identify interventions that might be implemented to improve healthy behaviors in this population. Methods: PubMed was searched using the following terms: “cancer[Tiab] AND young adult[Tiab] or teen[Tiab] or childhood[Tiab] AND prevention[Tiab] AND survivors[Meshterm].” Results: Twenty-seven articles were included. Children and AYA survivors of cancer have similar risk behaviors to their peers regarding tobacco, diet, and sun exposure. However, they have lower physical activity. Few studies on prevention strategies in this population were identified. Results of available studies remain inconclusive. No publications were found on occupational exposure and risk of second cancer. Conclusion: Children and AYAs treated for cancer are a population at risk and require specific effective prevention strategies.

In this retrospective study, we evaluate long-term complications in nearly all β-thalassemia-major patients who successfully received allogeneic hematopoietic stem cell transplantation in France. Ninety-nine patients were analyzed with a median age of 5.9 years at transplantation. The median duration of clinical follow up was 12 years. All conditioning regimens were myeloablative, most were based on busulfan combined with cyclophosphamide, and more than 90% of patients underwent a transplant from a matched sibling donor. After transplantation, 11% of patients developed thyroid dysfunction, 5% diabetes, and 2% heart failure. Hypogonadism was present in 56% of females and 14% of males. Female patients who went on to normal puberty after transplant were significantly younger at transplantation than those who experienced delayed puberty (median age 2.5 vs 8.7 years). Fertility was preserved in 9 of 27 females aged 20 years or older and 2 other patients became pregnant following oocyte donation. In addition to patient's age and higher serum ferritin levels at transplantation, time elapsed since transplant was significantly associated with decreased height growth in multivariate analysis. Weight growth increased after transplantation particularly in females, 36% of adults being overweight at last evaluation. A comprehensive long-term monitoring, especially of endocrine late effects, is required after hematopoietic stem cell transplantation for thalassemia.