Search

Background. Both thiotepa and its active metabolite, tepa, efficiently cross the blood-brain barrier. After intravenous administration, the cerebrospinal fluid concentrations achieved are nearly identical to those in plasma. This provides a strong rationale for testing this agent against brain tumors. Methods. Sixty pediatric patients with recurrent primary brain tumors were treated on a multiinstitutional Phase II study of intravenous thiotepa at a dose of 65 mg/[m.sup.2] administered every 3 weeks. This dose is the result of a prior pediatric Phase I trial and is significantly higher than those previously recommended. Results. Three of 13 assessable patients with medulloblastoma had partial responses lasting 22, 25, and 54 weeks. Although no objective responses were observed in 16 assessable patients with malignant gliomas and 14 with brain stem gliomas, 5 of 16 and 4 of 14 patients in these respective strata had prolonged periods of stable disease (SD) lasting from 12 to more than 33 weeks. Nine assessable patients with ependymoma had no objective response, but two had SD, both for more than 33 weeks. Myelosuppression was the principle toxic effect encountered and appeared to be more severe in patients who had received prior craniospinal radiation therapy or nitrosourea therapy. Conclusions. By conventional Phase II criteria, thiotepa appears to have activity in medulloblastoma. Based on several patients with prolonged SD, it also may possess some limited activity in brain stem and malignant gliomas. The steep in vitro dose-response curve of thiotepa and the long durations of response or SD observed with the dose reported here suggest that moderate-dose to high-dose thiotepa with cytokine support or autologous bone marrow rescue may be associated with an improved response rate to this agent.

Background. Ifosfamide with Mesna, given every other day over a 5-day period, was evaluated in 20 children with recurrent or progressive primary brain tumors. Methods. The patients were assigned to dosage cohorts separated on the basis of prior exposure to cisplatin (n = 10) or the absence of such exposure (n = 10). The initial dose in each treatment arm was 2133 mg/[m.sup.2] every other day for three doses, which represented 80% of the total dose delivered in our prior study of ifosfamide given daily over 5 days. The dose was escalated by 20% in each of the two subsequent cohorts (2560 mg/[m.sup.2] and 3072 mg/[m.sup.2] every other day for three doses). Results. The hematologic toxicity was dose limiting. Prior exposure to cisplatin did not seem to increase the hematologic toxicity. The most frequent and significant metabolic disturbance was hyponatremia, resulting in self-limited seizure activity in three patients. This complication was prevented in subsequent patients by changing the postifosfamide hydration fluids from 5% dextrose in quarter normal saline to 5% dextrose in normal saline. Conclusions. Although no child achieved a complete response, the activity of ifosfamide was demonstrated for a variety of tumors. The recommended dose of ifosfamide in a Phase II study for brain tumors is 3000 mg/[m.sup.2] given with Mesna every other day for three doses.

Neuroblastoma is a childhood tumor which arises from peripheral neuroblasts, the cells which form the peripheral nervous system during development. Commonly, the neuroblastoma arises from the same cells that form the adrenal medulla, a gland that is an important part of the sympathetic nervous system. Neuroblastoma does not occur within the brain and spinal cord, but these tissues may be affected by metastatic spread of the neuroblastoma. It is generally believed that when the brain or spinal cord is affected it is due to the extension of a metastatic neuroblastoma growing in an adjacent structure, such as bone. Until recently, it has been thought that the development of central nervous system (CNS) relapse in a child with neuroblastoma was an exceedingly grim sign. Six cases are now reported in which the prompt recognition and treatment of CNS involvement resulted in complete responses in four patients. In one of these patients the response continues to persist after more than five years. Two other patients were treated more recently and they continue to enjoy complete responses more than five and 27 months after CNS relapse from neuroblastoma. In a review of 160 cases of neuroblastoma, CNS involvement was identified in eight; two additional cases from another medical center were included in the present review. In four of the 10 cases, the disease was already too far advanced for any treatment attempt; these patients died within a week of presentation. The remaining six patients were treated with either radiation or chemotherapy containing platinum (such as cisplatin), or both. These cases illustrate that although CNS involvement of neuroblastoma is indeed a serious condition, treatment may nevertheless result in durable responses. (Consumer Summary produced by Reliance Medical Information, Inc.)

Cerebrovascular complications occur in up to 17 percent of children with sickle cell disease, in which abnormal hemoglobin (the oxygen-carrying protein in red blood cells) produces distorted, 'sickle-shaped' red blood cells and defective blood flow. Children under the age of 15 generally have cerebral infarcts (death of brain tissue due to lack of blood supply), while older patients tend to have hemorrhages. The incidence and severity of cerebrovascular accidents (CVAs) is less in patients given long-term transfusion therapy, but these patients are subject to other risks such as viral infection transmission (hepatitis or AIDS), transfusion reactions, and iron accumulation. Previous studies have suggested that the incidence of CVAs returns to normal if the duration of transfusion therapy is less than two years, while one study suggested that gradual tapering of transfusions after several years of intensive transfusions may be safe. To better determine the optimal duration of transfusion therapy, a study of sickle cell disease patients who had received at least five years of transfusions was initiated. The ages of the subjects ranged from 7 to 23 years; 16 and one half years was the average age at which transfusions were discontinued. Central nervous system (brain and spinal cord) status was evaluated before discontinuing therapy to identify abnormalities and risk factors associated with CVA. The study was terminated after the a sizable portion of the 10 patients who began the study developed a high incidence of CVAs. Among 10 patients, 23 major cerebral blood vessels were abnormal. Intellect was generally lower than normal; four patients were mildly or moderately impaired, and six had no significant functional impairment. Five of 10 patients had a stroke within one year of discontinuing transfusions. Details of each patient's condition are described. The study indicates that abruptly stopping transfusion therapy is unsafe, and further study is needed to determine how best to treat patients with sickle cell disease at risk for stroke. (Consumer Summary produced by Reliance Medical Information, Inc.)

A 10-year-old boy had a right posterior parietal glioblastoma 5 years after completing treatment for acute lymphoblastic leukemia. Interim findings included seizures, leukoencephalopathy, diffuse mineralizing micro-angiopathy, and abnormal changes in neuropsychological test performance, which, in retrospect, provided information about the location of the tumor. This case highlights unusual sequelae of childhood leukemia and its treatment, as well as the value of neuropsychological procedures in assessing functional status and integrity of the brain.

Sir.—Diarrhea and hypernatremic dehydration are common in infants being fed nasoenterally.1-4 We recently observed these complications in an infant transferred to our center after intraluminal migration of an adult-length weighted-tip enteral feeding tube. Occasionally, adult-length tubes are used in infants for routine nasogastric feeding. Our report is intended to alert pediatricians to the potential hazards of this practice and to suggest that the risk of complications can be reduced by using standard infant-sized nasogastric tubes.Patient Report.—A 2.1-kg female infant was delivered at 32 weeks' gestation after an uncomplicated pregnancy. A large immature teratoma involving the right temporal lobe was found during an examination because of apnea when the infant was 5 weeks old. Nasoenteral feeding with an 8-F × 102-cm radiopaque silicone elastomer feeding catheter with a silicone-weighted tip was begun after preoperative chemotherapy and craniotomy because of apnea and choking due to nasopharyngeal extension by