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Biomedical subjects

J Feusner

Publications and source records attributed to J Feusner.

29 records · Page 2Linked to original sources

A complex translocation, t(4;11;13)(q21;q23;q12-14), in a case of infantile acute lymphoblastic leukemia.

Cytogenetic analysis provides valuable prognostic information in children diagnosed with hematologic malignancies. While the t(4;11)(q21;q23) has frequently been reported in patients with acute lymphoblastic leukemia, the additional involvement of chromosome 13 to form a three-way translocation has not been described previously. We report a case of acute lymphoblastic leukemia in a 5-month old infant with a complex t(4;11;13)(q21;q23;q12-14).

Burkitt Lymphoma↗

Phase I and pharmacokinetic evaluation of all-trans-retinoic acid in pediatric patients with cancer.

PURPOSE: Recent reports of the dramatic antitumor effect of all-trans-retinoic acid (RA) in patients with acute promyelocytic leukemia (APL) have renewed interest in the oncologic indications for retinoids. Furthermore, a variety of pediatric tumors are responsive to RA in vitro, which provides additional rationale for a phase I evaluation of RA in children with cancer that is refractory to standard therapy. PATIENTS AND METHODS: A phase I trial of RA administered orally twice daily for 28-day treatment courses was performed. Cohorts of at least three pediatric cancer patients were entered at successive RA dose levels (from 45 to 80 mg/m2/d) until dose-limiting toxicity (DLT) was consistently observed. RESULTS: The maximum-tolerated dose (MTD) of RA was 60 mg/m2/d. Three of eight patients at the 80-mg/m2/d dose level developed reversible pseudotumor cerebri that necessitated discontinuation of the agent. Both patients with APL achieved complete remission (CR), whereas no patients with solid tumors had objective responses. Pharmacokinetic studies demonstrated a relatively short terminal half-life for RA (45 minutes), with diminution in plasma levels after chronic dosing. CONCLUSIONS: The MTD and recommended phase II dose for RA in children is 60 mg/m2/d given twice daily. Reversible CNS toxicity related to RA-induced pseudotumor cerebri is dose-limiting. Two children with APL achieved a CR to RA, which supports the inclusion of pediatric patients in clinical trials that evaluate the use of RA for patients with APL.

Administration, Oral↗

The surgical management of children with incompletely resected hepatic cancer is facilitated by intensive chemotherapy.

This prospective study was undertaken to evaluate the efficacy of continuous-infusion doxorubicin and cisplatin (CI-DOX/CPPD) for the treatment of children with incompletely resected hepatic cancer. Of the 46 evaluable patients, 32 had hepatoblastoma (70%) and 14 had hepatocellular carcinoma. Ten children had stage II tumors (microscopic residual), 25 were defined as stage III (gross residual), and 11 had distant metastasis (stage IV). Twelve patients underwent initial incomplete resection of their hepatic lesions and in the 34 others tumor biopsy specimens were obtained. Chemotherapy was administered and the majority of the children (70%) had an excellent clinical response with a decrease in both alpha-fetoprotein levels and measured tumor dimensions. The combination of CI-DOX/CPDD clearly facilitated surgical management, allowing for delayed hepatic resections in 20 of the 34 patients (59%) whose tumors were initially biopsied and considered to be unresectable. Overall survival in this study demonstrates a significant improvement in comparison to the historical controls. Twenty-one patients (46%) remain in complete clinical remission an average of 30 months following diagnosis (range, 17 to 40 months). The outcome of the children with hepatoblastoma was much better than those with hepatocellular carcinoma (63% v 17% survival). Survival of the 20 children who underwent delayed hepatic resections was not statistically different from the 12 patients whose hepatic tumors were removed at the initial laparotomy (41% v 58% survival). Although no obvious survival advantage was observed in those patients who underwent initial hepatic resections, there did appear to be an increased risk of postoperative complications in children whose tumors were resected following chemotherapy (8% v 25%).

Adolescent↗

Effective treatment of unresectable or metastatic hepatoblastoma with cisplatin and continuous infusion doxorubicin chemotherapy: a report from the Childrens Cancer Study Group.

The Childrens Cancer Study Group (CCSG) undertook a study (CCG-823F) to test the feasibility of administering continuous infusion doxorubicin (CI DOX) and cisplatin (CDDP) in patients with unresectable or incompletely resected hepatoblastoma (HB) or hepatocellular carcinoma (HCC). Chemotherapy consisted of CI DOX 20 mg/m2/d for days 1 to 4 and CDDP 100 mg/m2 on day 1 followed by a 21-day rest period. Second-look surgery was performed after the administration of four chemotherapy courses. Forty-seven (47) assessable patients were entered on study, 33 with HB and 14 with HCC; of these, 34 (26 HB and eight HCC) completed the initial four courses of chemotherapy. Of the 26 HB patients, 25 were evaluated as responding to chemotherapy before the scheduled second-look procedure and were considered surgically resectable at that time. Surgery was performed on 22 patients; three patients refused the second-look surgery. Nine patients had no evidence of residual malignant disease, seven underwent surgical resection of remaining tumor, four were left with microscopic residual disease, one had a partial resection with gross tumor left behind, and one remained unresectable. Nine HCC patients completed four chemotherapy courses. Eight patients achieved a partial remission and second-look surgery was attempted on seven. Only two had all malignant disease removed at the second procedure. Data from 225 courses of chemotherapy were evaluated for toxicity. Neutropenia (absolute granulocyte count less than 500/mL) was observed in 68 courses, and five of these episodes were associated with sepsis. Severe mucositis was documented in 21 courses, and hypomagnesemia (magnesium less than 1.2 mg) was noted in 30 patients. Two patients developed decreased left ventricular shortening fraction, which resolved when chemotherapy was discontinued. In summary, CI DOX plus CDDP is a well-tolerated and effective regimen in inducing surgical resectability in HB patients who are unresectable at diagnosis and significantly improves survival for this group of patients to 66.6%.

Adolescent↗

Use of routine chest radiography in the evaluation of fever in neutropenic pediatric oncology patients.

Evaluation of febrile episodes in children who have become neutropenic during treatment for malignant disease has traditionally included radiography of the chest. It has been our impression that the yield of such examination is low. To test this hypothesis we reviewed all chest radiographs (CXRs) obtained in the above setting in our institution over the last 3 years. These radiographs were independently reviewed by two of us (R.C., J.F.). Sixty-one patients experienced 134 febrile neutropenic episodes for which a CXR was obtained. Only eight (6%) of these films revealed any abnormality. After careful review it was apparent that four of these radiographs did not represent a infectious process. Thus only four of 134 films (2.9%) indicated pulmonary infection as the probable cause of fever in the patient. All four of these patients had prominent respiratory signs or symptoms. Of patients who were febrile but without pulmonary signs/symptoms, only one of 49 had an abnormal radiograph. We feel that such a low yield (at most 2%) calls into question the routine practice of obtaining a CXR in the febrile neutropenic child who is otherwise asymptomatic.

Adolescent↗

Hypertension in neuroblastoma induced by imipramine.

Hypertension is a well-known finding in some patients with neuroblastoma. However, it has not previously been described in association with the use of Imipramine. We report the occurrence of severe hypertension (blood pressure 190/160) in a 4-year-old girl with neuroblastoma who was given Imipramine to control a behavior disorder. It was determined later that this patient's tumor was recurring at the time of her hypertensive episode. Since she had no blood pressure elevation at initial diagnosis and none following discontinuation of the Imipramine (when she was in florid relapse), we believe that this drug rather than her underlying disease alone caused her hypertension. The mechanism for this reaction is believed to be increased levels of vasoactive catecholamines due to interference of their physiologic inactivation by Imipramine. From this experience, we urge extreme caution in the use of tricyclic antidepressants in children with active neuroblastoma.

Adrenal Gland Neoplasms↗

Altered central nervous system pharmacology of methotrexate in childhood leukemia: another sign of meningeal relapse.

CSF and plasma antifolate concentrations during 257 intravenous (IV) infusions of high-dose methotrexate were measured in 60 children with acute lymphoblastic leukemia. In 49 children who have never had evidence for CNS leukemia, the mean steady-state CSF to plasma methotrexate ratio was 0.013 (SD = 0.01). In contrast, 11 children with overt meningeal leukemia had a 12-fold higher mean ratio of 0.157 (range, 0.013 to 0.844, p less than .01). In the group of patients studied, all of those with a CSF methotrexate concentration greater than 2 SD above the mean either had leukemic cells in the CSF or subsequently developed this condition. In two patients, overt CNS leukemia was preceded by a high CSF:plasma drug ratio at a time when there was no cytologic or clinical evidence for CNS leukemia. As previously observed with intrathecal methotrexate, we conclude that overt meningeal leukemia increases CSF drug concentrations during IV methotrexate therapy. An elevated CSF to plasma ratio may be useful to predict imminent CNS relapse or to verify completeness of response to therapy.

Child↗

Sequential high-dose cytosine arabinoside-asparaginase treatment in advanced childhood leukemia.

Sequential high-dose cytosine arabinoside (ara-C) and asparaginase were given to 41 children age six months to 21 years of age with advanced leukemia. Ten of 22 patients with acute lymphocytic leukemia (ALL) and eight of 19 patients with acute nonlymphocytic leukemia (ANLL) obtained complete remissions. The most significant toxicity seen was infection in 22 patients. In addition, patients given intrathecal chemotherapy within 24 hours of ara-C developed neurologic toxicity. The high response rate seen in these patients with advanced leukemia indicates that a trial of this regimen is warranted in children with less advanced ALL and ANLL.

Acute Disease↗

Supportive care for children with cancer. Guidelines of the Childrens Cancer Study Group. The use of platelet transfusions.

The indications for platelet transfusions in pediatric oncology remain largely undefined. Results of clinical studies suggest that transfusing platelets prophylactically can reduce the incidence of bleeding during remission induction of acute leukemia, but they have not been shown to decrease deaths due to hemorrhage or to increase the overall survival of patients so treated. The risk of alloimmunization due to frequent platelet transfusions is not great, but it represents a life-threatening complication for some patients. Following a critical analysis of the literature, the author offers guidelines for indications of platelet transfusions, platelet dose, and the means of reducing the risk of alloimmunization. Although only patients with leukemia were included in the studies reviewed in this article, the author believes that the guidelines developed apply to children with other oncologic diagnoses as well.

Acute Disease↗