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To provide one of the first prospective reports examining neuropsychological outcomes for children treated with 1800 cGy whole brain radiotherapy (WBRT) and prophylactic chemotherapy versus prophylactic chemotherapy alone for acute lymphoblastic leukemia (ALL). Acute and long-term neuropsychological toxicities associated with WBRT are compared.This multisite study included 188 children, ages 4-21 years at enrollment, who were assessed with standardized neuropsychological tests at 9, 21, and 48 months after diagnosis with intermediate risk ALL. All participating children were receiving treatment on a parent study CCG105.Verbal intelligence (VIQ) scores for children receiving WBRT was significantly lower than VIQ for prophylactic chemotherapy at the 48-month time point (p 0.05). A significant cross-level interaction between time since diagnosis and treatment condition was observed (p 0.05). WBRT did not result in differences in PIQ; both groups of children demonstrated comparable increases in PIQ. Neuropsychological findings at 48 months after diagnosis indicated diminished performance in neuromotor, visual-motor coordination, and executive functioning for children receiving WBRT. Academic achievement was unaffected by WBRT at 4 years after diagnosis.The measurement of verbal and performance IQ as a primary endpoint in ALL clinical trials is critical to characterizing neuropsychological late effects. A trajectory of decline in neuropsychological functioning, specifically verbal IQ, was observed. Missing data within the trial occurred at random and did not impact results observed. The impact of WBRT becomes evident at 48 months after diagnosis, suggesting the need for long-term follow-up beyond the time frame typically used in Phase III trials.

Background. Andes virus (ANDV)–related hantavirus cardiopulmonary syndrome (HCPS) has a 35% case fatality rate in Chile and no specific treatment. In an immunomodulatory approach, we evaluated the efficacy of intravenous methylprednisolone for HCPS treatment, through a parallel-group, placebo-controlled clinical trial. Methods. Patients aged >2 years, with confirmed or suspected HCPS in cardiopulmonary stage, admitted to any of 13 study sites in Chile, were randomized by study center in blocks of 4 with a 1:1 allocation and assigned through sequentially numbered envelopes to receive placebo or methylprednisolone 16 mg/kg/day (≤1000 mg) for 3 days. All personnel remained blinded except the local pharmacist. Infection was confirmed by immunoglobulin M antibodies or ANDV RNA in blood. The composite primary endpoint was death, partial pressure of arterial oxygen/ fraction of inspired oxygen ratio ≤55, cardiac index ≤2.2, or ventricular tachycardia or fibrillation within 28 days. Safety endpoints included the number of serious adverse events (SAEs) and quantification of viral RNA in blood. Analysis was by intention to treat. Results. Infection was confirmed in 60 of 66 (91%) enrollees. Fifteen of 30 placebo-treated patients and 11 of 30 methylprednisolone-treated patients progressed to the primary endpoint (P= .43). We observed no significant difference in mortality between treatment groups (P=.41). There was a trend toward more severe disease in placebo recipients at entry. More subjects in the placebo group experienced SAEs (P= .02). There were no SAEs clearly related to methylprednisolone administration, and methylprednisolone did not increase viral load. Conclusions. Although methylprednisolone appears to be safe, it did not provide significant clinical benefi tt o patients. Our results do not support the use of methylprednisolone for HCPS. Clinical Trials Registration. NCT00128180.