Many pediatric and adolescent cancer patients are treated with carcinogenic chemotherapeutic agents and radiation therapy to achieve permanent control of their malignancy. These modalities may induce a new cancer in the successfully treated patient. To identify disease and treatment factors which increased the risk of occurrence of a second malignant tumor following modern treatment for cancer during childhood or adolescence, we reviewed the courses of 1,406 previously untreated patients who were less than 20 years of age at diagnosis and were treated at Roswell Park Cancer Institute between January 1, 1960 and December 31, 1989. Eighteen patients developed a second malignant tumor, including two meningiomas, 2.65-25.65 years after diagnosis of the first cancer. The actuarial risk of a second malignant tumor was 5.6% at 25 years after diagnosis. Using Cox proportional hazards modelling, we identified prior therapy with BCNU (P = 0.0055) and doxorubicin (P = 0.0254) as the only factors that were significantly associated with the risk of a second malignant tumor. Three second malignant tumors of the central nervous system occurred following treatment with a nitrosourea. Successfully treated patients must be carefully followed to identify treatment related malignant tumors at an early stage.

Bone marrow biopsies were prospectively performed on 75 patients with chronic lymphocytic leukemia (CLL). There was a highly significant relationship (p less than 0.002) between clinical stages and bone marrow infiltration patterns. Ten (50%) of 20 patients with diffuse patterns died; the estimated median survival time for these patients was 87 months. In contrast, only six (11%) of 55 patients with nondiffuse patterns died; the estimated median survival time for these patients could not be computed. When both clinical stage and infiltration pattern were evaluated for survival, a highly significant association between clinical stage and survival time was still observed (p less than 0.003) whereas bone marrow infiltration pattern was no longer significant. A significant association was also observed between bone marrow infiltration patterns and absolute lymphocyte counts (p less than 0.0005), Fc-receptor-positive cells (p less than 0.002), 3H-thymidine uptake of leukocytes (p less than 0.01), serum alkaline phosphatase levels (p less than 0.05), monoclonal urinary-free light chain status (p less than 0.05), and cytogenetics of leukemic cells (p less than 0.05). These observations lead to the conclusion that in an overall prognostic evaluation of patients with CLL, although bone marrow histopathology may have no additional value over a well-established clinical staging system, as a whole, it may be of clinically predictive value in disease progression of patients with stage I and II.

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In this randomised, double-blind, placebo-controlled, 2-year multicentre study intrathecally administered natural human fibroblast interferon (IFN-B) was effective in reducing exacerbations of multiple sclerosis (MS) in patients with exacerbating/remitting disease. The mean reduction in exacerbation rate of 34 patients who received IFN-B (recipients) was significantly greater during the study than that of 35 patients who received placebo (p less than 0.04). The prestudy exacerbation rates were comparable in recipients and controls, but the rate at the end of the study was significantly lower in recipients than in controls (p less than 0.001). IFN-B was given by nine or ten lumbar punctures over the first 6 months of the study, and patient observations continued for 2 years. IFN-B was well tolerated in 95% of the recipients, and the side-effects experienced were clearly acceptable for the benefits achieved. Low doses of indomethacin reduced the toxicity of IFN-B and played an important role in successful double-blinding.