Background. Osteonecrosis (ON) is a long-known complication of acute leukemia (AL) management affecting 1 to 10% of young patients, leading to long-term morbidity. Widespread access to Magnetic Resonance Imagery (MRI) over the past ten years has allowed earlier detection and more accurate assessment. This study investigated clinical and radiological features of ON, among the large French cohort L.E.A (Leucémie Enfant Adolescent) Procedure. Patients with ON were retrospectively enrolled and risk factors for the onset, the multifocal involvement and severe damage were analyzed. Quality of life (QoL) was also evaluated. A sub-study described radiological features. Results. 129/4973 patients developed ON (2.5%) and were preferentially aged over 10 years at time of AL diagnosis (OR 22.46, p <10-6). Females were preferentially affected (OR 1.8, p=0.002) like patients treated for relapse (OR 1.81, p=0.041). Patients presenting ON suffered more frequently from other sequelae (p<10-6). Most of the necrosis were involving weight-bearing joints and multiple joints in 69% of cases. MRI of 39 patients with ON were double blinded reviewed. Overall, 14/39 suffered from severe impairment, preferentially on hips. QoL of adolescents and adults was poor and permanently affected once ON occurred. Conclusions. Age of over 10 years at diagnosis of AL, relapse and female sex were at risk of developing ON involving preferentially multiple joints. One third was severe and lasting poor QoL impacting several domains was found. Future studies should include prospective data on management and biological genetic features to build a targeted screening program to detect and manage ON earlier.

Background The posttreatment period is a key part of the management of pediatric cancer care. At this period, psychosocial effects (scholarly and psychological difficulties) have been described in pediatric cancer patients and can be prognostic for the success of social reintegration. Psychosocial effects and their impact may be related to the household’s socioeconomic background. The aim of this study was to estimate psychosocial difficulties during the posttreatment period based on a social deprivation score. Design This study is based on a prospective multicentric study database, and focused on the children who had received psychosocial evaluation during their follow-up after cancer treatment since 01/01/2013. We retrieved data on their learning and psychological difficulties. Socioeconomic status of the household was estimated by a social deprivation score. Results 1003 patients were analyzed. Learning difficulties at school were noted in 22% of patients. A greater social deprivation was significantly associated with learning difficulty (OR=1.09 per unit of the deprivation score). Tumor relapse, treatment with hematopoietic stem cell transplantation, and diagnosis of a CNS tumor remained significant risk factors. In the subgroup analysis of children with CNS tumors, learning difficulties were increased and associated with greater social deprivation. By contrast, psychological difficulties were not associated with the deprivation score. Conclusion There is a link between SE status and learning difficulties in survivors of childhood cancer. Further investigations should be carried out to confirm these results for children with CNS tumors, which is the population of the greatest concern.

Chronic Granulomatous Disease (CGD) is a rare inherited disorder in which phagocytes lack NADPH oxidase activity. The most common form is the X-linked CGD (X-CGD), caused by mutations in the CYBB gene. Clinical, functional and genetic characterizations of 16 CGD cases of male patients and their relatives were done. We classified them as suffering from different variants of CGD (X910, X91− or X91+) according to NOX2 expression and NADPH oxidase activity in neutrophils. Twelve mutations were novel (10 X910-CGD and 2 X91− -CGD). One X910-CGD was due to a new and extremely rare double missense mutation Thr208Arg-Thr503Ile. We investigated the pathological impact of each single using stable transfection of each mutated cDNA in the NOX2 knock-out PLB-985 cell line. Both mutations leading to X91−-CGD were also novel; one deletion -67delT was localized in the promoter region of CYBB, the second one c.253-1879A>G mutation activates a splicing donor site, which unveils a cryptic acceptor site, leading to the inclusion of a 124-nucleotide pseudo-exon between exons 3 and 4 and responsible for the partial loss of NOX2 expression. Both X91−-CGD mutations were characterized by a low cytochrome b558 expression and a faint NADPH oxidase activity. The functional impact of new missense mutations is discussed in the context of a new 3D-model of the dehydrogenase domain of NOX2. Our study demonstrates that low NADPH oxidase activity found in both X91−-CGD patients correlates with mild clinical forms of CGD whereas X910-CGD and X91+-CGD cases remain the most clinically severe forms.

Introduction: Data regarding coronavirus disease 2019 (COVID-19) description are still limited in pediatric oncology. The French society of pediatric oncology (SFCE) has initiated a study to better describe the presentation and evolution of COVID-19 in patients followed in French pediatric oncology and hematology wards. Methods: All patients diagnosed with COVID-19 (polymerase chain reaction [PCR] positive for severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], or positive IgM serology, or chest computed tomography scan and clinical signs typical of COVID-19) and followed in a SFCE center were enrolled. Data from medical records were analyzed for all patients enrolled up to the end of May 2020. Results: Data was available for 37 patients. Thirty-one were children under 18 years of age. Nineteen patients were female. Seventeen patients had a solid tumor, 16 had a hematological malignancy and four recently underwent hematopoietic stem cell transplantation (HSCT) for non-oncological conditions. Twenty-eight patients presented symptoms, most often with fever, cough, rhinorrhea and asthenia. Ground-glass opacities were the most frequent radiological finding with abnormalities mostly bilateral and peripherally distributed. Twenty-four patients received chemotherapy a month prior to COVID-19 diagnosis. Most patients did not require hospitalization. Three patients required oxygen at the time of diagnosis. In total, five patients were admitted in an intensive care unit because of COVID-19 and one died from the disease. Conclusion: Children and young adults infected with SARS-CoV-2 and treated for a cancer and/or with a HSCT may be at risk for severe COVID-19 and should be closely monitored. (NCT04433871)