Malignant histiocytosis (MH) was diagnosed on the cytologic and cytochemical features of the malignant cells present in bone marrow smears from an infant and a child. The diagnosis of MH was confirmed by light and electron microscopic studies on bone marrow and skin biopsy specimens, and bone marrow and liver biopsy specimens, respectively. Both patients showed a deterioration while receiving prednisone monotherapy, but they responded well to a combination of vincristine and cyclophosphamide. The infant has remained disease‐free for 52+ months now, but the child died of a relapse 11 months after diagnosis. Cytogenetic studies of blood and/or bone marrow cells were performed before treatment. In the infant, a pathologic cell line with a translocation t(8;16)(p11;p13) was found; this abnormality was no longer present after remission was obtained. In the second patient, a hyperdiploid cell line with major karyotypic anomalies was found. When studied in relapse and shortly before death, additional chromosomal abnormalities were seen. The data from this study show that prednisone should be used with caution in MH, and that it should be omitted from combination chemotherapy when adverse effects are noted during short‐term monotherapy. Also, cytogenetic studies should be performed more often in MH to determine the significance and possible nonrandomness of chromosomal abnormalities in this disease.
To study the body distribution of 6-mercaptopurine (6MP), [8-14C]6MP was given by infusion to 2 marmoset monkeys at a dose rate of 5 mg/kg body weight/h for 1 and 4 h, respectively. Both experimental animals were sacrificed 2 h after the end of the drug infusion and instantly frozen at -70 degrees C. Whole-body sagittal sections were made later. Blood samples were obtained regularly during the experiments to quantitate 6MP, 6MP riboside (6MPR), 6-thioxanthine, and 6-thiouric acid in plasma. The autoradiograms revealed extensive distribution of the 14C label. High levels of radioactivity were seen in liver, bile, and intestinal contents. Labeling of the central nervous system and bone marrow was obvious. The plasma concentration-time curves of 6MP and 6MPR attained steady-state concentrations of 30-40 microM and 6-12 microM, respectively. After stopping the infusion of the drug, the concentrations of 6MP and 6MPR became equal. 6MPR contributes to the biological effect of 6MP, as degradation of 6MPR results in 6MP. In studies on the pharmacokinetics and dynamics one should try to include all relevant metabolites of 6MP, both in plasma and in the cells.
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