Management of diffuse glioma in children: a retrospective study of 27 cases and review of literature.

Gliomas are the most common CNS tumours in children and present either as circumscribed tumours or diffusely infiltrative neoplasms. Diffuse gliomas develop both in the cerebral hemispheres and the brainstem and have a poor prognosis. Guidelines for the therapy of these tumours are still debated. In this study, we reviewed the clinical features of 27 consecutive patients with diffuse gliomas admitted to the Department of Paediatrics of CHR Citadelle, University of Liège, between 1985 and 2005. We review their clinical presentation, diagnosis, treatment and outcome with reference to the published literature.

Effectiveness of early initiation of protease inhibitor-sparing antiretroviral regimen in human immunodeficiency virus-1 vertically infected infants.

Each of the 17 vertically infected infants born to HIV-1-infected mothers in Belgian HIV reference centers since 1996 was treated with a combination of 3 reverse transcription inhibitors as soon as the diagnosis was established. Treatment was initiated in all patients before 66 days of life. Twelve patients, including 11/13 infants treated with the combination of zidovudine, lamivudine and nevirapine, experienced a complete viral suppression (<50 copies/mL) with their first drug regimen. At last follow-up, 12 patients were asymptomatic, 2 were CDC stage A and 3 were stage B; 15 had HIV-1 RNA levels of <50 copies/mL and 14 had >or=25% CD4 lymphocytes. These results suggest that early initiation of treatment with 3 reverse transcription inhibitors is highly effective to inhibit viral replication and to prevent clinical and immunologic progression of HIV infection in vertically infected infants.

Resistance testing in children changing human immunodeficiency virus type 1 protease inhibitor.

OBJECTIVE: To assess genotypic and phenotypic resistance testing in HIV-1-infected children failing a first protease inhibitor (PI) therapy. METHODS: In a multicenter observational study 21 children, ages 3 to 16 years, were given two reverse transcriptase inhibitors and one PI (mainly ritonavir, n = 18). They were subsequently treated with single or dual PI-based therapy (predominantly nelfinavir, n = 10, or ritonavir-saquinavir, n = 7). Resistance testing was performed at the time of therapy switch via direct sequencing and a recombinant virus susceptibility assay. RESULTS: A total of 21 genotypic and 15 phenotypic resistance profiles were obtained. Most viruses displayed several reverse transcriptase mutations; however, 7 isolates maintained a wild-type protease. Ritonavir targeted the well-known pathway containing 82, 54, 46 and other secondary (nonactive site) mutations including T74A. No in vitro cross-resistance, i.e. > or = 8-fold resistance to saquinavir or amprenavir, was encountered. Secondary mutations enhanced the prediction of ritonavir resistance (i.e. L10I) and in vitro nelfinavir cross-resistance (i.e. K20R/I) conferred by primary (active site) resistance mutations. Either the 82, 54, 46 mutational genotype or the phenotype showing > or = 8-fold nelfinavir cross-resistance predicted a poorer virologic response to nelfinavir salvage therapy. CONCLUSION: In a small cohort of heavily pretreated pediatric patients, resistance testing appears to predict the response to nelfinavir as salvage for a ritonavir-based therapy. This is further supported by the correlation between ritonavir-selected mutations and in vitro nelfinavir cross-resistance. Prospective studies should assess clinical outcome in children undergoing regimen changes based on resistance testing.

Acute arrhythmogenicity of first-dose chemotherapeutic agents in children.

BACKGROUND: Chemotherapeutic agents have been reported to cause severe arrhythmias and sudden death in the first 24 hr after administration. In this prospective study, we determined the magnitude of acute arrhythmogenicity of those agents in children. PROCEDURE: Thirty-three patients with diverse malignancies (leukemia n = 16, Wilms tumor n = 3, brain tumor n = 3, lymphoma n = 3, others n = 8) were studied with Holter monitors 24 hr before, during, and in the first 24 hr following the first-dose therapy. RESULTS: Two patients experienced conduction disturbances (phases of 2nd degree sinuatrial and atrioventricular blocks) during a 4-hr period corresponding to a 30 mg/m(2) daunorubicin infusion. Eight patients experienced supraventricular extrasystole (SE), ventricular extrasystole (VE), and/or short salvos of supraventricular (SVT) and/or ventricular tachycardia (VT). Six had leukemia (therapy: daunorubicin + vincristine), one had a lymphoma (therapy: vincristine + cyclophosphamide), and the last one a brain tumor (therapy: carboplatin + procarbazine). Three patients with leukemia had pretreatment arrhythmias (1 VT, 2 SVT). One of them and the five other patients had arrhythmias during and after the first-dose therapy (2 VE, 2 SVT, 1 SVT + VE, 1 VE + SE + SVT). No patient had life-threatening arrhythmias and no prognostic value of those disturbances could be demonstrated. CONCLUSIONS: Conduction disturbances and arrhythmias are common in cancer children at the beginning of the therapy, but no acute or long-term adverse consequences are related to their appearance.