Biomedical subjects
Publications and source records attributed to M E Haggard.
Cerebral neuroblastoma is often difficult to differentiate by clinical criteria from other central nervous system neoplasm. This report is of a young child with cerebral neuroblastoma and elevated nerve growth factor. This case illustrates the need for further studies into the usefulness of nerve growth factor in differentiating cerebral neuroblastoma from other central nervous system tumors.
A 5-month-old infant with hypochromic anemia and iron overload secondary to ferrochelatase (heme synthetase) deficiency is described. Decreased activity of iron-containing enzymes in the absence of any other proven cause is suggested as the main cause of the associated growth retardation.
Twenty-six children greater than 1 year of age with previously untreated stage IV neuroblastoma were randomized to receive either a five-drug regimen (prednisone, cyclophosphamide, actinomycin D, vincristine, and daunorubicin) or a two-drug regimen (cyclophosphamide and vincristine). Complete response rates were 6% and 9% for the five-drug and the two-drug regimens respectively. Partial response rates were 13% and 27% for the five-drug and the two-drug regimens respectively. The mean duration of the seven responses was 9 months, and all 26 patients had died within 2 years. Neither regimen was effective for long-term disease control in these children with neuroblastoma.
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We have described a 9-year-old boy with progressive pigmentary dermatosis. The disease requires no treatment, but must be considered in the differential diagnosis of purpura in childhood to avoid unnecessary delay and concern to the patient.
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Twenty-five children with generalized histiocytosis X were treated with a combination of cyclophosphamide, vinblastine, and prednisone: 8 patients experienced complete response, 8 partial response, 2 imporvement, and 7 no response. Response rates for children over 1 year of age were higher than those reported for single agents. Twelve children are now off therapy with no evidence of disease for 10--50 months. Very poor response rates and high toxicity were seen in children less than 1 year of age. The two infants who eventually achieved CR did so by other therapies. Further trials in combination chemotherapy must weight possible long-term effects of such therapy against the prospect of more rapid disease control.
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Six regimens utilizing L-asparaginase in doses of 6,000 IU/M2, 2,000 IU/M2, and 500 IU/M2 in two separate schedules (consecutive and intermittent) along with vincristine and prednisone yielded remarkably similar response rates, approximating 70%, in 306 previously treated children with acute leukemia in relapse. The addition of daunorubicin to one regimen did not alter the response rate. Hypersensitivity reactions occurred in 5% and hyperglycemia in 7%. Lower doses of L-asparaginase significantly reduced the hypersensitivity rate but no such pattern was noted for hyperglycemia. A history of prior resistance to prednisone and vincristine significantly reduced the response rate.
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In the treatment of patients with meningeal leukemia, conventional intrathecal methotrexate therapy followed by maintenance intrathecal methotrexate at intervals of 8 weeks has been shown superior to an intensive, unmaintained intrathecal methotrexate induction regimen, and to neuroaxis radiotherapy, tumor dose 2000-2500 rads. In each of the treatment regimens, all children completing proscribed therapy achieved complete CNS remission as judged by the return of CSF findings to normal. Median lengths of remission were: maintenance regimen 240 days; intensive induction regimen, 106 days; and radiotherapy, 216 days. Differences were of statistical significance between the maintenance regimen and the intensive regimen (p equal 0.001), and between the radiotherapy and intensive regimens (p equal 0.01). Maintenance intrathecal therapy appeared to affect favorably the duration of existing marrow remissions; the median time to marrow relapse for patients given maintenance therapy was significantly longer than for those given intensive induction therapy. Toxicity of the chemotherapy regimens was not prohibitive. Radiotherapy was associated with severe myelosuppression, interruptions of systemic therapy, and serious infections, which resulted in death in five children.
A total of 180 children with acute leukemia was randomized to one of two induction regimens: vincristine plus prednisone, or 6-mercaptopurine plus prednisone. Of 170 patients evaluable for induction therapy, a hematologic remission was achieved in 83% (72/87) on vincristine plus prednisone, and in 93% (77/83) on 6-mercaptopurine plus prednisone. When hematologic remission was achieved, patients were randomized to one of three maintenance schedules: 6-mercaptopurine alone, 6-mercaptopurine plus prednisone for 4 weeks every 3 months, or 6-mercaptopurine plus prednisone plus vincristine for 4 weeks every 3 months. The durations of hematologic remission were compared from the achievement of hematologic remission to bone marrow relapse. The survival data were presented as an overview of the effect of this initial therapy on duration of survival. There was no statistical difference between the two induction regimens. The most important finding in the comparison of the three maintenance schedules was that reinforcement of 6-mercaptopurine maintenance therapy with either prednisone or prednisone plus vincristine resulted in significantly longer durations of remission. Vincristine added to prednisone for reinforcement after induction of remission by vincristine plus prednisone did not increase the duration of hematologic remission or survival over prednisone reinforcement alone.
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