Scedosporium prolificans endogenous endophthalmitis.

Scedosporium prolificans is an opportunistic fungus with a predilection for sepsis and endophthalmitis in immunocompromised patients. We report a case of endogenous S. prolificans endophthalmitis in a 9-year-old girl following chemotherapy for acute myeloid leukemia. She achieved an excellent visual outcome following intensive antifungal therapy.

Adverse hypersensitivity reactions to mesna as adjunctive therapy for cyclophosphamide.

Mesna is widely used for the prevention of cyclophosphamide-related hemorrhagic cystitis. It has been associated with hypersensitivity-like cutaneous and systemic reactions in adult patients. We report a series of children with malignant disease, who developed such reactions following mesna administration and discuss possible mechanisms and management issues.

Late magnetic resonance imaging features of leukoencephalopathy in children with central nervous system tumours following high-dose methotrexate and neuraxis radiation therapy.

High-dose methotrexate (HDMTX) is used increasingly to treat children with central nervous system (CNS) tumours. Although the neuro-imaging features of leukoencephalopathy associated with systemic or intrathecal methotrexate administered after cranial radiation have been well described, the extent to which the sequencing of HDMTX prior to cranial radiation in infants and children predisposes to late neuroradiological features of leukoencephalopathy is unknown. This report describes the National Cancer Institute (NCI) toxicity grade of leukoencephalopathy based on magnetic resonance imaging (MRI) findings in all patients who survived 4 or more years after treatment on an earlier phase II study. These patients, with newly diagnosed CNS embryonal tumours, were in the age range 3.5-14.2 years (median 6.9 years) at diagnosis, and received four courses of pre-irradiation combination chemotherapy, including HDMTX 8 g/m(2). Following completion of the 'up-front' phase II study, all patients received conventionally fractionated whole brain doses of 36-50.4 Gy. The radiation dose and treatment volumes were determined individually according to the primary tumour location and results of extent of disease evaluations. The most recent MRI brain scans, obtained 4.0-10.5 years (median 6.5 years) after radiation therapy and comprising a minimum of T1, T1 following gadolinium and T2 sequences, were reviewed centrally to assess the neuroradiological grade of leukoencephalopathy, based on the NCI Common Terminology Criteria for Adverse Events, v3.0. Grade I changes (mild increase in subarachnoid space, and/or mild ventriculomegaly, and/or small/focal T2 hyperintensities) were evident in 8 of the 12 patients and grade II changes (moderate increase in subarachnoid space and/or moderate ventriculomegaly, and/or focal T2 hyperintensities extending to the centrum ovale) were found in the remaining 4. In conclusion, treatment with multiple courses of HDMTX prior to 36-50.4 Gy cranial radiation did not result in moderate to severe MRI features of leukoencephalopathy. Future studies in paediatric neuro-oncology patients, involving HDMTX combined with prospective neuropsychological evaluations appear justified.

Advances in childhood leukaemia: successful clinical-trials research leads to individualised therapy.

In most cases, childhood leukaemia has a fetal origin, but multiple molecular events are required after birth for pre-leukaemic cells to progress to leukaemia. Cure rates for acute lymphoblastic leukaemia (ALL) now approach 80%. A high level of minimal residual disease detected by polymerase chain reaction in patients with ALL in remission has profound prognostic importance and is the focus of a major Australian study attempting to prevent relapse in these children. Greater awareness of the late effects of chemotherapy has led to changes in the treatment protocols for ALL, with improvement in neurocognitive outcomes and reduced rates of second malignancies. Pharmacogenetics is a new field of research that aims to enhance treatment efficacy by assessing the individual's metabolism of and response to chemotherapeutic agents. Targeted therapies currently being developed show some promise of being able to further improve cure rates. Adolescents with ALL have a better prognosis if treated with paediatric rather than adult protocols.

Activity of postoperative carboplatin, etoposide, and high-dose methotrexate in pediatric CNS embryonal tumors: results of a phase II study in newly diagnosed children.

BACKGROUND: Chemotherapy is used as an alternative to irradiation or to minimize the irradiation exposure among infants with medulloblastoma or other CNS embryonal tumors. Adjuvant chemotherapy is commonly used in older children with high-risk medulloblastoma to improve survival or to allow a reduction in the craniospinal irradiation dose in standard-risk patients. However, optimal multimodality therapy, including the precise role of chemotherapy, has not been defined for these groups of patients. The objective of the present study is to assess the efficacy and toxicity of four postoperative courses of carboplatin, etoposide, and high-dose methotrexate in newly diagnosed children with medulloblastoma or other CNS embryonal tumors. PROCEDURE: Twenty-eight children, aged from 0.3 to 15.9 years (median, 6.2 years) with post-operative measurable residual CNS embryonal tumors were enrolled, comprising medulloblastoma (n = 19), supratentorial PNET (n = 7), and pineoblastoma (n = 2). Post-operative chemotherapy comprised carboplatin 350 mg/m(2) and etoposide 100 mg/m(2) on Days 1 & 2, and methotrexate 8 g/m(2) on Day 3, repeated at 21-28-day intervals for a total of four courses. Therapy following completion of the initial Phase II study was influenced by patient age and investigator preference. RESULTS: The combined complete response rate (CR, 7/19) and partial response rate (PR, 7/19) was 74% in patients with medulloblastoma, 89% for patients with PNET/pineoblastoma (CR, 2/9 and PR, 6/9), and for all patients it was 79%. Patients aged < 3 years at diagnosis had a combined PR and CR rate of 71% compared to 81% in patients aged > 3 years. Treatment was well tolerated although myelosuppression and thrombocytopenia were common. CONCLUSIONS: The combination of carboplatin, etoposide, and high-dose methotrexate is highly active in pediatric patients with CNS embryonal tumors.