Clustering of variants into functional classes correlates with cancer risk and identifies different phenotypes of Li-Fraumeni syndrome.

Li-Fraumeni syndrome (LFS) is a heterogeneous predisposition to an individually variable spectrum of cancers caused by pathogenic germline variants. We used a clustering method to assign TP53 missense variants to classes based on their functional activities in experimental assays assessing biological p53 functions. Correlations with LFS phenotypes were analyzed using the public germline mutation database and validated in three LFS clinical cohorts.

Quality of Life Priorities of Childhood Acute Lymphoblastic Leukemia Survivors Enrolled in EORTC Studies, and a Comparison of Instruments.

Purpose: Survivors of childhood cancer can suffer from long-term sequelae or decline in quality of life (QoL), for which careful and standardized selection of outcome measures become more important. This study aims to assess different QoL-related outcomes using three distinct questionnaires in an international study, identify the priorities of childhood ALL survivors via the administered questionnaires, and investigate potential interrelationships among QoL domains across the questionnaires.

Methods: Childhood ALL survivors treated according to the EORTC CLG treatment protocols 58741, 58831/2, and 58881 were recruited in Belgium and France and answered self-report QoL questionnaires, including the Short-Form Health Survey 12 (SF12), the Quality-of-Life Systemic Inventory (QLSI), and the Impact of Cancer for Childhood Cancer Survivors (IOC-CS).

Results of the prospective EORTC Children Leukemia Group study 58081 in precursor B- and T-cell acute lymphoblastic leukemia.

Here, we report the results of the prospective cohort study EORTC-CLG 58081 and compare them to the control arm of the randomized phase 3 trial EORTC-CLG 58951, on which treatment recommendations were built. In both studies, patients aged 1-18 years with negative acute lymphoblastic leukemia of the B-lineage (B-ALL) or T-lineage (T-ALL) were treated using a BFM backbone without cranial irradiation. Similarly to the control arm of 58951, prednisolone (PRED) 60 mg/m/day was used for induction therapy, but a few modifications were made.

40 years of forest dynamics and tree demography in an intact tropical forest at M'Baïki in central Africa.

A vast silvicultural experiment was set up in 1982 nearby the town of M'Baïki in the Central African Republic to monitor the recovery of tropical forests after disturbance. The M'Baïki experiment consists of ten 4-ha Permanent Sample Plots (PSPs) that were assigned to three silvicultural treatments in 1986 according to a random block design. In each plot, all trees with a girth at breast height greater than 30 cm were spatially located, numbered, measured, and determined botanically.

Long-term neurotoxicity among childhood acute lymphoblastic leukaemia survivors enrolled between 1971 and 1998 in EORTC Children Leukemia Group studies.

Survival after childhood acute lymphoblastic leukemia (ALL) has increased over the last 40 years with an overall survival above 90%. Survivors may experience neurological late effects secondary to chemotherapy and radiotherapy. This observational retrospective study evaluated the cumulative incidence of neurological late effects among 890 childhood ALL survivors treated in EORTC CLG trials (58741, 58831/2 and 58881) between 1971 and 1998.

A systematic review of the prevalence of pathogenic or likely pathogenic germline variants in individuals with FOXO1 fusion-positive rhabdomyosarcoma.

Several cancer predisposition syndromes (CPS) are reported to predispose to rhabdomyosarcoma, most frequently in children with embryonal rhabdomyosarcoma. There are lingering questions over the role of CPS in individuals with alveolar rhabdomyosarcoma (ARMS), which are frequently driven by FOXO1 fusion oncoproteins. We conducted a systematic review to identify patients with FOXO1 fusion-positive ARMS (FP-ARMS) who underwent germline DNA sequencing.

Weaning from noninvasive ventilatory support in infants with severe bronchiolitis: An observational study.

Background: The aim of the study was to analyze the weaning success, the type of weaning procedures, and weaning duration in consecutive infants hospitalized in a pediatric intensive care unit over a winter season.

Methods: A retrospective observational study was conducted in a pediatric intensive care unit in a tertiary center. Infants hospitalized for severe bronchiolitis were included and the weaning procedure from continuous positive airway pressure (CPAP), noninvasive ventilation (NIV), or high-flow nasal cannula (HFNC) was analyzed.

Quality of life of long-term childhood acute lymphoblastic leukemia survivors: Comparison with healthy controls.

Objective: Improved treatment landscape has led to better outcomes for paediatric acute lymphoblastic leukemia (ALL) survivors. As the number of survivors increase, we need to elucidate the long-term quality of life (QoL) and domains of complaints in these patients. Furthermore, the main priorities of these patients need to be clarified.

Socio-economic outcomes among long-term childhood acute lymphoblastic leukaemia survivors enrolled between 1971 and 1998 in EORTC CLG studies: Results of the 58LAE study.

Objective: The objective of this study is to evaluate the socio-economic outcomes of survivors of childhood acute lymphoblastic leukaemia (ALL).

Methods: Childhood ALL adult survivors, enrolled in EORTC trials between 1971 and 1998 in France and Belgium, were invited to fill out a questionnaire with information about their socio-economic situation (living with a partner, having a university degree, having a job, working part time and history of having a paid job). The outcomes were compared with two matched control populations.

The French FRACTURE database: A way to improve knowledge on management of children with very rare tumors.

Introduction: Very rare pediatric tumors (VRTs), defined by an annual incidence ≤2 per million inhabitants, represent a heterogeneous group of cancers. Due to their extremely low incidence, knowledge on these tumors is scant. Since 2012, the French Very Rare Tumors Committee (FRACTURE) database has recorded clinical data about VRTs in France.

Genotype-phenotype associations within the Li-Fraumeni spectrum: a report from the German Registry.

Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by pathogenic TP53 variants. The condition represents one of the most relevant genetic causes of cancer in children and adults due to its frequency and high cancer risk. The term Li-Fraumeni spectrum reflects the evolving phenotypic variability of the condition.

Novel Insights into Pediatric Acute Lymphoblastic Leukemia Ophthalmic Relapses from a Nationwide Cohort Study.

Ten to fifteen percent of children with acute lymphoblastic leukemia (ALL) relapse following treatment. Of these, less than 2% display ophthalmic relapses, which owing to their scarcity, are largely undocumented, leaving clinicians with few diagnostic and therapeutic recommendations, despite serious functional sequelae. We conducted a French multicenter retrospective study to collect all clinical, radiological, biological, and therapeutic data, and outcomes for children with ALL ophthalmic relapses.

Long-Term Clinical and Psychiatric Complications of Young Adults Cured of a Pediatric Bone Tumor Diagnosed Between 1987 and 1999 in Rhône: Alpes Region (France).

The 5-year survival for children diagnosed with cancer is ∼85%. The constant increase in survival curves is evidence of therapeutic optimization. Clinical and psychological complications are rarely analyzed simultaneously in the literature for pediatric malignant bone tumors.

Sociodemographic and Medical Determinants of Quality of Life in Long-Term Childhood Acute Lymphoblastic Leukemia Survivors Enrolled in EORTC CLG Studies.

Background: due to increasing survival rates in childhood acute lymphoblastic leukemia (ALL), the number of survivors has been expanding. A significant proportion of these survivors can experience long-term emotional and psychosocial problems. However, the exact risk factors remain inconclusive.

High-dose chemotherapy followed by autologous stem cell rescue in Wilms tumors: French report on toxicity and efficacy.

Background: Heterogeneous data have been reported on high-dose chemotherapy (HDCT) with autologous stem cell rescue (ASCR) in Wilms tumors (WTs). We aimed to define its safety and efficacy in the French cohort, and to compare this management to current international recommendations.

Methods: Data prospectively collected from children, adolescents, and young adults with WT treated with HDCT/ASCR between 2000 and 2016 in French centers were retrospectively analyzed.

Fertility status among long-term childhood acute lymphoblastic leukaemia survivors enrolled between 1971 and 1998 in EORTC CLG studies: results of the 58 Late Adverse Effects study.

Study Question: What are the fertility outcomes of male and female childhood acute lymphoblastic leukaemia (ALL) long-term survivors?

Summary Answer: We observed similar fertility outcomes in both male and female childhood ALL survivors compared with the general population, with the exception of a higher proportion of miscarriages among partners of male survivors.

What Is Known Already: Survival after childhood ALL is currently >90% and fertility impairments are among the main concerns of the long-term survivors. Few studies have focused on the fertility issues within this selected population and the existing data are difficult to interpret due to the different treatment regimens received by the patients, the small sample sizes and the unavailability of control data in many studies.

Analysis of the Li-Fraumeni Spectrum Based on an International Germline TP53 Variant Data Set: An International Agency for Research on Cancer TP53 Database Analysis.

Importance: Li-Fraumeni syndrome is a cancer predisposition syndrome that is associated with a high, lifelong risk of a broad spectrum of cancers that is caused by pathogenic TP53 germline variants. A definition that reflects the broad phenotypic spectrum that has evolved since the gene discovery is lacking, and mechanisms leading to phenotypic differences remain largely unknown.

Objective: To define the phenotypic spectrum of Li-Fraumeni syndrome and conduct phenotype-genotype associations across the phenotypic spectrum.

Recurrent bacterial infections, but not fungal infections, characterise patients with ELANE-related neutropenia: a French Severe Chronic Neutropenia Registry study.

Among 143 patients with elastase, neutrophil-expressed (ELANE)-related neutropenia enrolled in the French Severe Chronic Neutropenia Registry, 94 were classified as having severe chronic neutropenia (SCN) and 49 with cyclic neutropenia (CyN). Their infectious episodes were classified as severe, mild or oral, and analysed according to their natural occurrence without granulocyte-colony stimulating factor (G-CSF), on G-CSF, after myelodysplasia/acute leukaemia or after haematopoietic stem-cell transplantation. During the disease's natural history period (without G-CSF; 1913 person-years), 302, 957 and 754 severe, mild and oral infectious events, respectively, occurred.

CNS-3 status remains an independent adverse prognosis factor in children with acute lymphoblastic leukemia (ALL) treated without cranial irradiation: Results of EORTC Children Leukemia Group study 58951.

Aim: To evaluate the prognostic significance of initial central nervous system (CNS) involvement of children with acute lymphoblastic leukemia (ALL) enrolled in the EORTC 58951 trial.

Patients And Methods: From 1998 to 2008, 1930 ALL patients were included in the randomized EORTC 58951 trial. Overall treatment intensity was adjusted according to known prognostic factors including the level of minimal residual disease after induction treatment.

Invasive Fungal Infections in Immunocompromised Children: Novel Insight Following a National Study.

Objective: To obtain a national overview of the epidemiology and management of invasive fungal infections (IFIs) in France for severely immunocompromised children who were treated for acute leukemia or had undergone allogeneic hematopoietic stem cell transplantation (a-HSCT).

Study Design: We performed a national multicenter retrospective study to collect epidemiologic data for proven and probable IFIs in children with acute leukemia under first- line or relapse treatment or who had undergone a-HSCT. We also conducted a prospective practice survey to provide a national overview of IFI management in pediatric hematology units.

A calf-level study on colostrum management practices associated with adequate transfer of passive immunity in Québec dairy herds.

The objective of this study was to identify the calf-level colostrum management practices associated with an adequate transfer of passive immunity (TPI; defined as serum Brix refractance ≥8.4% in the first week of life) in small-sized herds. A total of 818 calves from 61 commercial Holstein dairy farms were included in this observational cross-sectional study.

A herd-level study on colostrum management factors associated with the prevalence of adequate transfer of passive immunity in Québec dairy herds.

The objective of this study was to identify herd-level colostrum management factors associated with the adequate transfer of passive immunity (TPI; defined as serum Brix refractance ≥8.4% in the first week of life). A total of 59 commercial Holstein dairy farms were included in this observational cross-sectional study.