Relevance of Molecular Groups in Children with Newly Diagnosed Atypical Teratoid Rhabdoid Tumor: Results from Prospective St. Jude Multi-institutional Trials.

Purpose: Report relevance of molecular groups to clinicopathologic features, germline alterations (GLA), and survival of children with atypical teratoid rhabdoid tumor (ATRT) treated in two multi-institutional clinical trials.

Materials And Methods: Seventy-four participants with newly diagnosed ATRT were treated in two trials: infants (SJYC07: age < 3 years; = 52) and children (SJMB03: age 3-21 years; = 22), using surgery, conventional chemotherapy (infants), or dose-dense chemotherapy with autologous stem cell rescue (children), and age- and risk-adapted radiotherapy [focal (infants) and craniospinal (CSI; children)]. Molecular groups ATRT-MYC (MYC), ATRT-SHH (SHH), and ATRT-TYR (TYR) were determined from tumor DNA methylation profiles.

Risk-adapted therapy for young children with medulloblastoma (SJYC07): therapeutic and molecular outcomes from a multicentre, phase 2 trial.

Background: Young children with medulloblastoma have a poor overall survival compared with older children, due to use of radiation-sparing therapy in young children. Radiotherapy is omitted or reduced in these young patients to spare them from debilitating long-term side-effects. We aimed to estimate event-free survival and define the molecular characteristics associated with progression-free survival in young patients with medulloblastoma using a risk-stratified treatment strategy designed to defer, reduce, or delay radiation exposure.

Novel Combined Immune Deficiency and Radiation Sensitivity Blended Phenotype in an Adult with Biallelic Variations in and .

With the advent of high-throughput genomic sequencing techniques, novel genetic etiologies are being uncovered for previously unexplained Mendelian phenotypes, and the underlying genetic architecture of disease is being unraveled. Although most of these "mendelizing" disease traits represent phenotypes caused by single-gene defects, a percentage of patients have blended phenotypes caused by pathogenic variants in multiple genes. We describe an adult patient with susceptibility to bacterial, herpesviral, and fungal infections.

Fanconi anemia and biallelic BRCA2 mutation diagnosed in a young child with an embryonal CNS tumor.

Medulloblastoma, the most common pediatric malignant brain tumor often arises sporadically; however, in a subgroup of patients, there exist familial conditions such as Fanconi anemia with biallelic BRCA2 mutation that predispose patients to developing medulloblastoma. Biallelic inactivation of BRCA2 in Fanconi anemia has been previously described in only 11 patients with medulloblastoma in the literature to date. Here we report two siblings diagnosed with central nervous system embryonal tumors at an early age in association with biallelic BRCA2 inactivation, including the first reported case of a spinal cord primitive neuroectodermal tumor (PNET) in a BRCA2/FANCD1 kindred.

M1 Medulloblastoma: high risk at any age.

Background: The prognosis for children with M1 medulloblastoma (positive CSF cytology) has not been well-defined.

Methods: We retrospectively reviewed the records of 285 newly diagnosed medulloblastoma patients treated between 1984 and 2006. Older children received post-operative craniospinal and tumor bed irradiation; radiotherapy for younger children depended on treatment era and physician/family preference.

Young age may predict a better outcome for children with diffuse pontine glioma.

Background: Because diffuse pontine glioma (DPG) is rare among young children, the outcome of affected patients is unknown.

Methods: The authors reviewed clinical and radiologic characteristics of all children aged <3 years with DPG who were evaluated at their institution. Inclusion followed standard magnetic resonance imaging criteria for the diagnosis of DPG.

Endocrine outcomes for children with embryonal brain tumors after risk-adapted craniospinal and conformal primary-site irradiation and high-dose chemotherapy with stem-cell rescue on the SJMB-96 trial.

Purpose: To estimate the cumulative incidence of specific hormone deficiencies and the influence of hypothalamic-pituitary (HP) axis radiation dose in a cohort of children with embryonal brain tumors treated with risk-adapted craniospinal irradiation (CSI), conformal primary site irradiation, and high-dose chemotherapy.

Patients And Methods: Clinical data and HP axis radiation dosimetry data were obtained from 88 eligible children. All patients received regular endocrine follow-up that included screening tests of thyroid function and stimulation testing for growth hormone deficiency (GHD), and adrenocorticotropin hormone deficiency.

High-grade astrocytoma in very young children.

Background: High-grade astrocytomas are rare in young children, but have been reported to have a better prognosis than similar tumors in older patients.

Procedure: We retrospectively reviewed the clinical characteristics, survival, and long-term sequelae for patients younger than 3 years old with high-grade astrocytoma, treated at a single institution between 1984 and 2005.

Results: Sixteen patients were included.

A revised classification scheme for acute transfusion reactions.

Background: Although the standard classification system for acute transfusion reactions adequately describes the general features associated with the various types of reactions, it was not designed to provide strict criteria for diagnosis and classification. Consequently, its use to classify individual reactions can result in significant inter- and intraobserver variability, which can complicate patient management and clinical research.

Study Design And Methods: A total of 595 transfusion reactions that occurred at a single institution between January 1, 1996, and December 31, 2003, were reviewed and were initially classified according to the established conventions of the AABB.

Reinduction of relapsed acute promyelocytic leukemia with ATRA and low dose antimetabolite-based chemotherapy.

While the disease-free survival of acute promyelocytic leukemia (APML) now approaches 75%, some children continue to experience relapses, and questions remain as to the optimal management of these patients. We describe two young children who experienced combined relapses in the bone marrow and extramedullary locations following hematopoietic stem cell transplantation (HSCT). An induction regimen, consisting of all-trans retinoic acid (ATRA), methotrexate, and 6-mercaptopurine (6MP), successfully and safely achieved hematologic remission in one patient and molecular remission in the other.

Premedication with acetaminophen or diphenhydramine for transfusion with leucoreduced blood products in children.

Febrile non-haemolytic or allergic reactions occur in 0.1-30% of transfusions; physicians often premedicate patients with acetaminophen or diphenhydramine to prevent these reactions. The effectiveness of this practice has not been demonstrated.

Familial adenomatous polyposis in two brothers with hepatoblastoma: implications for diagnosis and screening.

Two brothers with hepatoblastoma were noted to have a family history of early onset colon cancer. Genetic testing of the younger brother revealed a deletion in exon 15 of the adenomatous polyposis coli (APC) gene (2710-2711delAG), consistent with a diagnosis of familial adenomatous polyposis (FAP). We review the clinical and molecular aspects of the relationship between hepatoblastoma and FAP, and the implications for diagnostic testing and cancer screening in affected patients.

Telomerase expression predicts unfavorable outcome in osteosarcoma.

Purpose: Osteosarcoma is distinct from most cancers in that the majority of osteosarcomas lack telomerase expression and use the alternative lengthening of telomeres (ALT) mechanism to maintain telomeres. Laboratory studies suggest that compared with ALT, telomerase expression is associated with increased tumor aggressiveness. We evaluated the clinical significance of telomerase expression in human osteosarcoma.