Double trouble: A case of fraternal twins with iron-refractory iron-deficiency anemia.

Iron-refractory iron-deficiency anemia (IRIDA) is a rare autosomal recessive disease that presents in childhood. We report the case of fraternal twins presenting with severe hypochromic microcytic anemia and hypoferritinemia. Two missense mutations affecting the gene were identified, consistent with IRIDA.

Optimized peripheral blood progenitor cell mobilization for autologous hematopoietic cell transplantation in children with high-risk and refractory malignancies.

Background: Autologous hematopoietic stem cell transplantation (aHSCT) using hematopoietic progenitor cells (HPCs) has become an important therapeutic modality for patients with high-risk malignancies. Current literature on standardized method for HPC apheresis in children is sparse and failure rate reported as high as 30%.

Patients/methods: A retrospective study of 125 pediatric patients with high-risk malignancies undergoing aHSCT in Western Australia between 1997 and 2016 was conducted.

Hematopoietic stem cell transplantation for children with acute myeloid leukemia in second remission: A report from the Australasian Bone Marrow Transplant Recipient Registry and the Australian and New Zealand Children's Haematology Oncology Group.

Background: Approximately one-third of children with acute myeloid leukemia (AML) relapse, requiring re-treatment and allogeneic hematopoietic stem cell transplantation (HSCT). Although achieving second complete remission (CR2) prior to HSCT is desirable, once CR2 is attained, it is unclear if there is any benefit from further chemotherapy prior to HSCT. Moreover, although pre-HSCT minimal residual disease (MRD) has prognostic value in acute lymphoblastic leukemia, the benefit of MRD reduction after achieving CR prior to HSCT is less clear for AML.

Exercise training improves vascular function and secondary health measures in survivors of pediatric oncology related cerebral insult.

Adolescent and young adult (AYA) survivors of pediatric oncology related cerebral insult are vulnerable to numerous treatment-induced deficits that significantly enhance cardiovascular disease risk. Regular exercise improves endothelial function, fitness, body composition and musculoskeletal function which may reduce predisposition for cardiovascular disease. Here we assessed the feasibility and effectiveness of a 24-week exercise intervention on cardiovascular, physical and metabolic outcomes in this population.

Automated enumeration of lymphoid and plasma cells in bone marrow to establish normal reference ranges.

Aims: The number of precursor and mature lymphoid cells and plasma cells in normal bone marrow trephine (BMT) biopsies throughout the human lifespan is unknown. Reference ranges have been established from aspirated marrow, but due to haemodilution errors, these do not accurately reflect the native marrow milieu. We aimed to define age-specific, normal reference ranges for lymphoid and plasma cells in BMT biopsy specimens using a combined immunophenotyping and digital enumeration approach.

Metabolic and Psychological Impact of a Pragmatic Exercise Intervention Program in Adolescent and Young Adult Survivors of Pediatric Cancer-Related Cerebral Insult.

Purpose: To assess metabolic function among adolescent and young adult (AYA) survivors of childhood cancer-related brain surgery or cranial irradiation (CRT) and to determine feasibility, safety, and metabolic as well as psychological impact of a 6-month exercise program in this cohort.

Methods: Twenty AYAs aged 15-23 years were recruited. All had completed cancer treatment by age 15.

The case for DNA methylation based molecular profiling to improve diagnostic accuracy for central nervous system embryonal tumors (not otherwise specified) in adults.

Central nervous system primitive neuro-ectodermal tumors (CNS-PNETs), have recently been re-classified in the most recent 2016 WHO Classification into a standby catch all category, "CNS Embryonal Tumor, not otherwise specified" (CNS embryonal tumor, NOS) based on epigenetic, biologic and histopathologic criteria. CNS embryonal tumors (NOS) are a rare, histologically and molecularly heterogeneous group of tumors that predominantly affect children, and occasionally adults. Diagnosis of this entity continues to be challenging and the ramifications of misdiagnosis of this aggressive class of brain tumors are significant.

Fitness, body composition and vascular health in adolescent and young adult survivors of paediatric brain cancer and cranial radiotherapy.

Background Survivors of paediatric brain cancer and/or cranial radiotherapy (CRT) are at an increased risk of developing serious comorbidities. Established risk factors for chronic disease include central obesity, endothelial abnormalities and diminished fitness. Objectives Here we characterised anthropometry, body composition, bone mineral density (BMD), heart rate (HR), blood pressure (BP), endothelial function, muscular strength and endurance and aerobic fitness in adolescent and young adult (AYA) survivors.

Immunogenicity and safety of single-dose, 13-valent pneumococcal conjugate vaccine in pediatric and adolescent oncology patients.

Background: Children receiving immunosuppressive treatment for cancer are at high risk for invasive pneumococcal disease. The 13-valent pneumococcal conjugate vaccine (PCV13) can prevent pneumococcal disease in healthy children; however, there is an absence of literature regarding the benefit of PCV13 in immunocompromised children with cancer.

Methods: A prospective, open-label cohort study recruited children between ages 1 and 18 years who were receiving active immunosuppressive therapy (AIT) or were within 12 months after completing immunosuppressive therapy (CIT).

Heterogeneity in mechanisms of emergent resistance in pediatric T-cell acute lymphoblastic leukemia.

Relapse in pediatric T-cell acute lymphoblastic leukemia (T-ALL) remains a significant clinical problem and is thought to be associated with clonal selection during treatment. In this study we used an established pre-clinical model of induction therapy to increase our understanding of the effect of engraftment and chemotherapy on clonal selection and acquisition of drug resistance in vivo. Immune-deficient mice were engrafted with patient diagnostic specimens and exposed to a repeated combination therapy consisting of vincristine, dexamethasone, L-asparaginase and daunorubicin.

Immunogenicity and clinical effectiveness of the trivalent inactivated influenza vaccine in immunocompromised children undergoing treatment for cancer.

Influenza is associated with significant morbidity and mortality in children receiving therapy for cancer, yet recommendation for, and uptake of the seasonal vaccine remains poor. One hundred children undergoing treatment for cancer were vaccinated with the trivalent inactivated influenza vaccine according to national guidelines in 2010 and 2011. Influenza-specific hemagglutinin inhibition antibody titers were performed on blood samples taken prior to each vaccination and 4 weeks following the final vaccination.

Increased Body Mass Index during Therapy for Childhood Acute Lymphoblastic Leukemia: A Significant and Underestimated Complication.

Objective & Design. We undertook a retrospective review of children diagnosed with acute lymphoblastic leukemia (ALL) and treated with modern COG protocols (n = 80) to determine longitudinal changes in body mass index (BMI) and the prevalence of obesity compared with a healthy reference population. Results.

Joint Aspiration for Acute Hemarthrosis in Children Receiving Factor VIII Prophylaxis for Severe Hemophilia: 11-year Safety Data.

Objective: The aims of this study were (1) to document the prevalence of acute hemarthrosis in a cohort of 46 boys with severe hemophilia A receiving full primary prophylaxis in Western Australia (WA), and (2) to investigate the safety of the WA protocol over 11 years for management of hemarthrosis.

Methods: Case review. The WA protocol involves a pediatric rheumatologist washing out all acute hemarthrosis of large joints promptly and then instilling intraarticular (IA) corticosteroids.

Rare childhood cancers--an increasing entity requiring the need for global consensus and collaboration.

Rare childhood cancers have not benefited to the same extent from the gains that have been made for their frequently occurring counterparts. In recent years, this gap has been recognized and a number of vehicles now exist to improve outcome, including rare tumor groups, disease-specific registries, and clinics. The multitude of approaches has allowed significant progress, however, this framework is limited by patient number and is not inclusive for every type of rare childhood cancer.

Lessons from 50 years of curing childhood leukaemia.

One of the great success stories of modern medicine is undoubtedly the remarkable improvement in outcome for childhood cancer, achieved through the work of the co-operative groups enrolling patients in randomised controlled trials. In 1965, survival was almost zero; now 5-year survival rates exceed 80% in high-income countries. The lessons learned in the care of patients with the most common malignancy in childhood--acute lymphoblastic leukaemia--have been used in all other cancers of childhood and more recently in the management of adults.

Deregulated expression of connective tissue growth factor (CTGF/CCN2) is linked to poor outcome in human cancer.

Connective tissue growth factor (CTGF/CCN2) has long been associated with human cancers. The role it plays in these neoplasms is diverse and tumour specific. Recurring patterns in clinical outcome, histological desmoplasia and mechanisms of action have been found.

Connective tissue growth factor is expressed in bone marrow stromal cells and promotes interleukin-7-dependent B lymphopoiesis.

Hematopoiesis occurs in a complex bone marrow microenvironment in which bone marrow stromal cells provide critical support to the process through direct cell contact and indirectly through the secretion of cytokines and growth factors. We report that connective tissue growth factor (Ctgf, also known as Ccn2) is highly expressed in murine bone marrow stromal cells. In contrast, connective tissue growth factor is barely detectable in unfractionated adult bone marrow cells.

Hepatic sinusoidal obstruction syndrome during chemotherapy for childhood medulloblastoma: report of a case and review of the literature.

Hepatic sinusoidal obstruction syndrome (HSOS), also known as veno-occlusive disease, is a well-recognized toxic complication after autologous and allogeneic hematopoietic stem cell transplant, during treatment of Wilms tumor and rhabdomyosarcoma associated with actinomycin-D, and during acute lymphoblastic leukemia therapy due to oral 6-thioguanine. However, its occurrence in the context of chemotherapy regimens for other childhood malignancies is rare. We report a 5-year-old girl with high-risk anaplastic medulloblastoma, who developed severe HSOS during her second cycle of maintenance chemotherapy, consisting of vincristine, cisplatin, and cyclophosphamide.

Medulloblastoma Down Under 2013: a report from the third annual meeting of the International Medulloblastoma Working Group.

Medulloblastoma is curable in approximately 70% of patients. Over the past decade, progress in improving survival using conventional therapies has stalled, resulting in reduced quality of life due to treatment-related side effects, which are a major concern in survivors. The vast amount of genomic and molecular data generated over the last 5-10 years encourages optimism that improved risk stratification and new molecular targets will improve outcomes.

Morbidity in survivors of child and adolescent meningioma.

Background: The extent of initial surgical resection has been identified as the strongest prognostic indicator for survival in child and adolescent meningioma. Given the paucity of data concerning long-term outcome, the authors undertook a meta-analysis to analyze morbidity in survivors of this disease.

Methods: Individual patient data were obtained from 19 case series published over the last 23 years through direct communication with the authors.

Inflammatory and haematological markers in the maternal, umbilical cord and infant circulation in histological chorioamnionitis.

Background: The relationship between histological chorioamnionitis and haematological and biochemical markers in mothers and infants at delivery, and in infants postnatally, is incompletely characterised. These markers are widely used in the diagnosis of maternal and neonatal infection. Our objective was to investigate the effects of histological chorioamnionitis (HCA) on haematological and biochemical inflammatory markers in mothers and infants at delivery, and in infants post-delivery.