We compared two regimens with respect to their ability to prolong disease-free survival in 506 children and adolescents with acute lymphocytic leukemia. All responders to induction therapy were randomized to treatment with 2400 rad of cranial irradiation plus intrathecal methotrexate or to treatment with intermediate-dose methotrexate plus intrathecal methotrexate, as prophylaxis for involvement of the central nervous system and other "sanctuary" areas. Patients were then treated with a standard maintenance regimen. Complete responders were stratified into either standard-risk or increased-risk groups on the basis of age and white-cell count at presentation. Among patients with standard risk, hematologic relapses occurred in 9 of 117 given methotrexate and 24 of 120 given irradiation (P less than 0.01). The rate of central-nervous-system relapse was higher in the methotrexate group (23 of 117) than in the irradiation group (8 of 120) (P = 0.01). Among patients with increased risk, radiation offered greater protection to the central nervous system than methotrexate (P = 0.03); there was no difference in the rate of hematologic relapse. In both risk strata the frequency of testicular relapse was significantly lower in the methotrexate group (1 patient) than the radiation group (10 patients) (P = 0.01). Methotrexate offered better protection against systemic relapse in standard-risk patients and better protection against testicular relapse overall, but it offered less protection against relapses in the central nervous system than cranial irradiation.
We have examined the primary immune responses, the numbers of total T (T11+) cells, T-helper (T4+) cells, T-suppressor (T8+) cells, and natural killer (NK) (Leu7+) cells, in 118 healthy control subjects and compared the data to those obtained from 20 patients with clinically diagnosed malignant mesothelioma and 375 long-term asbestos workers without neoplasia. The absolute numbers of total T (T11+) and T-helper (T4+) cells were normal in asbestos workers without neoplasia but were significantly reduced in patients with mesothelioma. T-suppressor (T8+) cells, on the other hand, remained unchanged in the patients but were significantly elevated among the asbestos workers. This resulted in a marked reduction in T-helper (Th) to T-suppressor (Ts) ratios in mesothelioma patients and in asbestos workers. Seventy percent of the mesothelioma patients (14 of 20) had significantly depressed NK-cell activity which could be augmented but not normalized by coincubation in patients' peripheral blood lymphocytes (PBL) with interferon (IFN). Among the asbestos workers three distinctive subgroups could be identified: heightened (H-NK), normal (N-NK), and low (L-NK) NK activity. The NK activity of the L-NK group could be stimulated but not normalized by coincubation with IFN, a finding closely resembling that in malignant mesothelioma patients. Phenotyping of the circulating NK cells revealed a unique Leu7+ subset in increased numbers with a brightly fluorescent property in stable mesothelioma patients with relatively stable or slowly progressive disease and in more than 30% of the asbestos workers.(ABSTRACT TRUNCATED AT 250 WORDS)
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