Summary: Peripheral blood mononuclear cells from 45 children, aged 1 to 19 years were evaluated for natural killer cell cytotoxic activity against K-562 erythroleukemic cells, The results of a 51Cr release assay demonstrated that the NK cell activity of normal children is dependent on age and sex. Younger females, aged 1 to 9 years, were more reactive than elder females aged between 10 and 19 years (P<0.001). Males aged 1 to 19 years were less reactive than adults (0.02 < P < 0.05). Among children, the levels of NK cell activity were significantly greater in females than in males (0.001 < P < 0.01). In con trast, among elder children, the levels of NK cell activity were significantly greater in males than in females (0.01 < P < 0.02). The NK cell activity of elder female children was 60% and 59% that of the elder male children, at the two E : T ratios of 50:1 and 100:1, respectively.

High-dose methotrexate(H-D MTX) therapy followed by citrovorum factor rescue is now widely used for the treatment of childhood malignant tumors. To understand pharmacokinetics and toxicity of H-D MTX (50-300 mg/ kg), we measured plasma and urine levels of the subject after a total of 170 infusions to 16 children. The samples were obtained 12, 24 and 48hr after the beginning of 6 hr infusion. Two phases of plasma MTX disappearance were seen after infusion: the first phase (12-24 hr) had a half-life 2.28-3.27 hr and the second phase (24-48 hr) 6.96-8.74 hr. Significant correlation was obtained between dosage and plasma levels on concentration curve. With the same dose, the younger patients (under 8 years) had low plasma MTX levels, as compared with the older patients (over 13 years). After H-D MTX infusion, severe toxicities such as myelosuppression, abnormal kidney function and stomatitis were observed in 2 cases. We consider that the maximum allowable plasma MTX levels be 10-5M at 24hr and 10-6M at 48hr, on the basis of the finding that the plasma MTX levels in these cases exceeded those levels, respectively, at the same hours. From the beginning of H-D MTX infusion, cumulative urinary excretion in the first 12hr was greater than 50% of the administered dose. Our data suggest that in view of the safety of H-D MTX therapy, monitoring of plasma MTX levels and adequate hydration be important, especially for the older patients.

A 5-month-old-girl had hepatomegaly and severe anemia. Based on the multiple imaging studies, hemangioendothelioma was suspected. Wedge resection of the liver and hepatic artery ligation were performed. The peripheral blood film showed pancytopenia, and the myelogram showed markedly reduced erythroid series and myeloid predominance with shift to the left. The correlation between hemangioen$othelioma and bone marrow dysfunction is unknown.As far as we know, this is the first report of infantile hemangioendothelioma associated with bone marrow dysfunction.

Sixteen children with Stage III and N neuroblastoma were treated using two different chemotherapy protocols; six with a James' therapy plus adriamycin, and ten with a regimen consisting of high-dose cyclophosphamide, vincristine and adriamycin in a nonrandomized fashion. The highdose cyclophosphamide with vincristine and adriamycin appeared to improve the duration of survival; that is, in the patients treated by this protocol, the median survival duration was 25 months, the one-year survival rate was 75% and the three-year survival rate was 50%. On the other hand, none of the patients treated by James' therapy plus adriamycin survived for more than one year. Their median survival was only four months.

Thirty-four children with acute lymphoblastic leukemia (ALL) and 45 normal children as controls were tested for natural killer (NK) cell activity in vitro using the K-562 cell line as target cell.In the group of patients off all chemotherapy, the levels of NK cell activity were found to be comparable to normal controls. The levels o f activity in the intermittent chemotherapy group were higher than or the same as those of normal controls. Low levels of NK cell activity were observed, shortly after intermittent chemotherapy. Patients who had more than two remissions had levels of NK cell activity comparable to normal controls. In contrast, low levels of NK cell activity were found in patients shortly before relapse, but returned to normal levels after achieving complete remission. Significant differences in the clinical stages between relapse and remission were found by paired t-test analysis (0.02 < p < 0.05).