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BACKGROUND: Venoocclusive disease (VOD) of the liver is a common complication after allogenic and autologous bone marrow transplantation for malignant disease. The authors report the unusual and unexpected complication of VOD of the liver occurring in children with rhabdomyosarcoma who were receiving vincristine, actinomycin D, and cyclophosphamide (VAC) according to the chemotherapy regimens of the Intergroup Rhabdomyosarcoma Study (IRS) IV. METHODS: The authors evaluated 821 patients with newly diagnosed rhabdomyosarcoma receiving treatment according to IRS IV who were considered at risk for VOD. RESULTS: Ten patients developed VOD of the liver for an overall incidence of 1.2%. VOD was found only after the administration of VAC chemotherapy. The highest incidence of VOD was observed among patients who had previously received vincristine and melphalan (Regimen 48). None of the patients receiving the chemotherapy regimen of vincristine and actinomycin D (Regimen 44) developed VOD. CONCLUSIONS: Patients receiving VAC-containing regimens on the IRS IV were found to be at risk for VOD. The VAC combination was used extensively in previous IRS studies (I, II, and III) and VOD was not reported during these studies, strongly suggesting that the escalation of the cyclophosphamide dose to 2.2 g/m2 (with the vincristine and actinomycin D doses and schedule remaining unchanged) triggered the development of VOD. The contributing role of previous therapy or events is unknown. At last follow-up, none of the nine surviving patients had developed recurrent VOD on continuation of chemotherapy.
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This study determines the utility of gallium-67 (Ga-67) scintigraphs as an adjunct to computed tomography (CT) scans for the assessment of residual mediastinal masses in children and adolescents with advanced-stage Hodgkin's disease. At diagnosis 42 patients with CT scan-documented mediastinal disease had a Ga-67 scan performed. Thirty-four of 42 patients (81%) had gallium-avid mediastinal lesions, whereas in eight (19%), the Ga-67 scan was negative. At the completion of eight cycles of therapy of Mustargen (mechlorethamine), Oncovin (vincristine), procarbazine, prednisone (MOPP) alternating with doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD), 21 of 34 patients with initially positive Ga-67 scans had them repeated; 18 of 21 converted to negative results, and three remained positive. In 11 of 18 patients, the loss of gallium avidity was consistent with a negative mediastinal CT scan. In seven, although the gallium scan was negative, the CT scan remained positive; all seven patients had a mediastinal biopsy of suspected residual disease and in all seven the biopsy results were negative for Hodgkin's disease. These preliminary results in a small cohort of patients demonstrate that Ga-67 scans may be of benefit in evaluating residual mediastinal masses in patients with Hodgkin's disease.
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Congenital anomalies were identified in 37 of 115 (32%) children and adolescents autopsied with rhabdomyosarcoma. An analysis of sex, age, site, and histology of cases with or without congenital anomalies showed no significant differences. Of the 45 identified anomalies, 14 were considered major and 31 minor. The distribution of the anomalies by system included central nervous (9), genitourinary (10), gastrointestinal (13), and cardiovascular systems (4). Ten patients had complex or miscellaneous anomalies. There was one child with each of the following: Rubinstein-Taybi syndrome, neurofibromatosis, single horseshoe kidney, hemihypertrophy, and Arnold-Chiari malformation. Aniridia was not noted in any case of rhabdomyosarcoma. Individuals with rhabdomyosarcoma have an increased incidence of genitourinary anomalies similar to that in Wilms' tumor. Recent molecular genetic investigations have suggested that rhabdomyosarcoma, Wilms' tumor, and hepatoblastoma share a common pathogenetic mechanism involving chromosome 11. The uniquely increased association of central nervous system anomalies with rhabdomyosarcoma and absence of aniridia would support a different gene locus operative on chromosome 11 for individuals with rhabdomyosarcoma compared to Wilms' tumor. Extensive epidemiologic studies now in progress in patients with rhabdomyosarcoma should provide the incidence of congenital anomalies and potential linkage with prenatal events.
This study was designed to test if the activity of a phase II agent, ifosfamide, would have been underestimated if it was tested exclusively in a population of children and young adults with recurrent osteosarcoma. The response rate to ifosfamide was compared in patients younger than 30 years of age with previously untreated osteosarcoma with metastases at diagnosis and/or unresectable primary tumors (stratum 1) with that of patients with recurrent osteosarcoma following adjuvant chemotherapy who were not previously exposed to ifosfamide (stratum 2). Evaluation of response was conducted 3 weeks after two courses of ifosfamide (2400 mg/m2 x 5 days) were administered 3 weeks apart. Nine of 33 (27%) evaluable patients in stratum 1 responded (1 complete and 8 partial responses) to ifosfamide. Among 30 evaluable patients in stratum 2, only 3 (10%) responded (1 complete and 2 partial responses; P = .04) Both groups of patients received equal doses of ifosfamide and experienced comparable toxicities. Results from this study suggest that the activity of new agents will be underestimated if tested in a population of heavily pretreated patients with recurrent disease. When possible, new chemotherapeutic agents should be tested in patients with a poor prognosis who have not been exposed to chemotherapy.
PURPOSE: The objectives of this study were to evaluate the feasibility of reducing therapy, while maintaining treatment efficacy, in the context of a cooperative group clinical trial that allowed for clinical staging in early stage Hodgkin disease (HD). PATIENTS AND METHODS: Between August 1992 and December 1993, 51 eligible children < or =21 years of age, 31 male and 20 female, were enrolled in this study which was designed for low stage (IA, IIA, IIIA1) HD. Laparotomy and surgical staging was optional. Five postpubertal patients with Stage IA and IIA disease received only involved-field radiation therapy. The other 46 patients, who form the basis of this report, received combined modality therapy consisting of four courses of doxorubicin, bleomycin, vincristine, and etoposide (DBVE) followed by 2,550 cGy involved-field irradiation. RESULTS: With a median follow-up of 8.4 years, the 6-year overall and event-free survival rates for the 46 patients treated with combination therapy were 98 +/- 2% and 91 +/- 5%, respectively. All patients achieved remission after completion of therapy. There have been four recurrences and a remission death due to gunshot wound. Combined modality therapy was well tolerated. Predominant side effects were gastrointestinal and hemopoietic. There have been no clinically significant cardio-pulmonary side effects so far. CONCLUSION: In clinically staged children with early-stage HD, DBVE and low-dose involved-field irradiation was effective therapy with tolerable side effects and reduced potential for long-term adverse events.
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Forty-two patients with progressive solid tumors and brain tumors were entered in this Phase I study of the glutamine antagonist acivicin given intravenously over thirty minutes daily for five days. The major toxicities encountered were myelosuppression and central nervous system toxicity (nightmares and somnolence). The maximum tolerated dosage on this schedule was 26 mg/M2 daily for five days. Six patients including three patients with brain tumor had stable disease.
Numerous epidemiological studies about multiple trauma patients do not include an analysis of patients under the age of 18. To study this, the data of 682 patients with multiple traumata, treated between 1981 and 1991 at Hannover Medical School, Germany, were retrospectively analyzed. The patients were divided into four age-related groups: preschool age (< 6 years), school age (< 13 years), teenagers (< 18 years) and adults (> or = 18 years). Analyzed were the cause of trauma, localization of injuries and the cause of death. Children were less often injured as passengers in cars, but more often injured as pedestrians and bicyclists than adults. However, children showed a significant higher mortality than adults, with threefold increased risk of death when they injured as passengers in car accidents. In all groups injuries to the head and the legs were most common. Children showed a lower incidence of trauma to the thorax, abdomen, hip and arms than the adult group. Nevertheless, trauma to the thorax, abdomen and head was associated with the highest risk of death in all groups. Spinal cord injuries, especially injuries to the neck, also showed a high risk of death. Children younger than 6 years had the most severe head injuries. Safety improvements for children in cars, helmet usage on bicycles and early training in traffic safety for children might decrease the lethality in this group of trauma patients.
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