A 1-Year Prospective French Nationwide Study of Emergency Hospital Admissions in Children and Adults with Primary Immunodeficiency.

Purpose: Patients with primary immunodeficiency (PID) are at risk of serious complications. However, data on the incidence and causes of emergency hospital admissions are scarce. The primary objective of the present study was to describe emergency hospital admissions among patients with PID, with a view to identifying "at-risk" patient profiles.

Incidence and risk factors for clinical neurodegenerative Langerhans cell histiocytosis: a longitudinal cohort study.

Neurodegenerative (ND) complications in Langerhans cell histiocytosis (LCH) are a late-onset but dramatic sequelae for which incidence and risk factors are not well defined. Based on a national prospective registry of paediatric LCH patients, we determined the incidence rate of clinical ND LCH (cND-LCH) and analysed risk factors, taking into account disease extent and molecular characteristics. Among 1897 LCH patients, 36 (1·9%) were diagnosed with a cND-LCH.

Does ATRX germline variation predispose to osteosarcoma? Three additional cases of osteosarcoma in two ATR-X syndrome patients.

Osteosarcoma is the most common malignant bone tumor in adolescents and young adults. Most osteosarcomas are sporadic but the risk of osteosarcoma is also increased by germline variants in TP53, RB1 and RECQL4 genes. ATRX germline variations are responsible for the rare genetic disorder X-linked alpha-thalassemia mental retardation (ATR-X) syndrome characterized by severe developmental delay and alpha-thalassemia but no obvious increased risk of cancer.

Circulating cell-free BRAF as a biomarker in children with Langerhans cell histiocytosis.

The BRAF mutation is reported in half of patients with Langerhans cell histiocytosis (LCH). This study investigated the detection of the BRAF allele in circulating cell-free (ccf) DNA in a paediatric LCH cohort. Children with BRAF -mutated LCH were investigated to detect ccf BRAF at diagnosis (n = 48) and during follow-up (n = 17) using a picolitre-droplet digital PCR assay.

BRAF Mutation Correlates With High-Risk Langerhans Cell Histiocytosis and Increased Resistance to First-Line Therapy.

Purpose: Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia with a broad spectrum of clinical manifestations and outcomes in children. The somatic BRAF(V600E) mutation occurs frequently, but clinical significance remains to be determined.

Patients And Methods: BRAF(V600E) mutation was investigated in a French LCH cohort.

Langerhans cell histiocytosis: therapeutic strategy and outcome in a 30-year nationwide cohort of 1478 patients under 18 years of age.

The French national cohort of children with Langerhans cell histiocytosis (LCH) has included 1478 patients since it was established in 1983. LCH therapeutic strategies substantially changed in 1998, so we have divided the cohort into two 15-year periods. Starting in 1998, therapy duration increased from 6 to 12 months, repeated induction therapy was performed in cases showing a poor response to the first induction with vinblastine and steroids, and refractory disease in a risk organ (RO+) was treated with cladribine and cytarabine.

Oncologic Phenotype of Peripheral Neuroblastic Tumors Associated With PHOX2B Non-Polyalanine Repeat Expansion Mutations.

Background: Germline non-polyalanine repeat expansion mutations in PHOX2B (PHOX2B NPARM) predispose to peripheral neuroblastic tumors (PNT), frequently in association with other neurocristopathies: Hirschsprung disease (HSCR) or congenital central hypoventilation syndrome (CCHS). Although PHOX2B polyalanine repeat expansions predispose to a low incidence of benign PNTs, the oncologic phenotype associated with PHOX2B NPARM is still not known in detail.

Methods: We analyzed prognostic factors, treatment toxicity, and outcome of patients with PNT and PHOX2B NPARM.

Rearrangement of HMGA2 in a case of infantile lipoblastoma without Plag1 alteration.

Lipoblastoma is a rare benign adipocytic tumor that occurs usually in children. It can be difficult to distinguish a lipoblastoma from other lipogenic tumors. In such cases, the detection of a rearrangement of the PLAG1 gene by fluorescence in situ hybridization analysis is useful for characterizing a lipoblastoma.

Signalling and chemosensitivity assays in melanoma: is mutated status a prerequisite for targeted therapy?

Selection for targeted therapies in melanoma is currently based on the search for mutations in selected genes. We aimed at evaluating the interest of signalling and chemosensitivity studies in addition to genotyping for assessing the best suitable treatment in an individual patient. We extracted genomic DNA and melanoma cells from tumor tissue of a skin metastasis of a 17-year-old woman with stage IV melanoma progressing despite three successive lines of treatment.

Long-term evaluation of Ifosfamide-related nephrotoxicity in children.

Purpose: Ifosfamide is widely used in pediatric oncology but its nephrotoxicity may become a significant issue in survivors. This study is aimed at evaluating the incidence of late renal toxicity of ifosfamide and its risk factors.

Patients And Methods: Of the 183 patients prospectively investigated for renal function, 77 treated for rhabdomyosarcoma, 39 for other soft tissue sarcoma, 39 for Ewing's sarcoma, and 28 for osteosarcoma were investigated at least 5 years after treatment.

Adjuvant corticosteroid therapy in 2 children with hepatosplenic candidiasis-related IRIS.

First described in HIV-infected patients who recently initiated highly active antiretroviral therapy, the immune reconstitution inflammatory syndrome (IRIS) is best characterized as a collection of inflammatory disorders triggered by rapid resolution of immunosuppression. Treatment of IRIS is a clinical challenge due to the variety of clinical presentations and the presence of multiple pathogens capable of causing the syndrome. Hepatosplenic candidiasis, an uncommon form of invasive Candida species infection, was recently suggested to belong to the spectrum of fungus-related IRIS.

Noninvasive procedures to evaluate liver involvement in HIV-1 vertically infected children.

Objectives: : Progressive liver injury is a concern in HIV-infected children exposed to long-term antiretroviral drugs and to the cytopathic effect of HIV. Yet liver biopsy is usually considered too invasive to be repeated in these patients. The aims of this study are to evaluate the feasibility of noninvasive hepatic investigations in HIV-1-infected children, assess the prevalence of signs of liver affection, and analyse the influence of the HIV disease severity and the exposure to antiretroviral therapy.

MR features of isolated uterine relapse in an adolescent with acute lymphoblastic leukaemia.

Relapses of lymphoblastic leukaemia traditionally involve the central nervous system and testes in boys. Involvement of the female pelvic organs is frequently found at autopsy; however, involvement of the cervical uterus is rare and even less commonly symptomatic. A 13-cm uterine mass was discovered in a 15-year-old adolescent with a history of lymphoblastic leukaemia during childhood.

Germline mutations of the paired-like homeobox 2B (PHOX2B) gene in neuroblastoma.

Hereditary predisposition to neuroblastoma accounts for less than 5% of neuroblastomas and is probably heterogeneous. Recently, a predisposition gene has been mapped to 16p12-p13, but has not yet been identified. Occurrence of neuroblastoma in association with congenital central hypoventilation and Hirschsprung's disease suggests that genes, involved in the development of neural-crest-derived cells, may be altered in these conditions.

Germline mutations of the paired-like homeobox 2B (PHOX2B) gene in neuroblastoma.

Neuroblastoma (NB) is a frequent pediatric tumor for which recurrent somatic rearrangements are known. Germline mutations of predisposing gene(s) are suspected on the basis of rare familial cases and the association of NB with other genetically determined congenital malformations of neural crest-derived cells--namely, Hirschsprung disease (HSCR) and/or congenital central hypoventilation syndrome (CCHS). We recently identified the paired-like homeobox 2B (PHOX2B) gene as the major disease-causing gene in isolated and syndromic CCHS, which prompted us to regard it as a candidate gene in NB.

Clinical, immunologic and genetic analysis of 29 patients with autosomal recessive hyper-IgM syndrome due to Activation-Induced Cytidine Deaminase deficiency.

Mutations of the Activation-Induced Cytidine Deaminase (AID) gene have been found in patients with autosomal recessive hyper-IgM (HIGM) syndrome type 2. We retrospectively analyzed clinical, immunologic and genetic characteristics of 29 patients from 22 families with AID deficiency. Patients' median age at diagnosis and at last evaluation was 4.

Incidence of growth hormone deficiency in pediatric-onset Langerhans cell histiocytosis: efficacy and safety of growth hormone treatment.

We retrospectively studied 61 patients with GH deficiency (GHD), identified among 589 patients with Langerhans cell histiocytosis (LCH) enrolled in a nationwide survey between 1993 and 2001. Overall, 141 patients in the survey developed diabetes insipidus. The median follow-up of the 61 patients with GHD was 12 yr.