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Urinary polyamine levels were determined in patients with acute leukemia, before and during chemotherapy, in order to confirm whether tumor cell death, due to successful chemotherapy, increases the release in urine and serum of polyamines from tumor tissues (12). Comparison between the polyamine test and cytological data indicated that a rise in urinary spermidine levels occurs during the first 3 days of therapy, both in the responsive and unresponsive patients. However, in the responsive patients the spermidine increase was higher (at 5% significant level) than in the unresponsive ones, and it was coincident with the fall of the blast cells and the revival of normal hematopoiesis. Increases in putrescine levels were also observed, but there were no significant differences (5% level) between the 2 groups of patients. When polyamine determinations were carried out following chemotherapy cycles, the relapse of the disease was always accompanied by an increase in putrescine.

Two cases of acute leukaemia, one monoblastic and one myelomonocytic, in which hypokalaemia, hypomagnesaemia and hypocalcaemia were documented, are reported. Urinalysis demonstrated renal loss of potassium and magnesium without other evidence of renal tubular dysfunction. The mechanism and clinical significance of these abnormalities are briefly discussed.

Two cases of the development of acute myeloid leukemia (AML) after treatment with alkylating agents are reported. In Case 1, melphalan and then cyclophosphamide had been given for multiple myeloma. 46 months after onset of cytostatic treatment AML occurred, as confirmed cytochemically and by qualitative determination of urinary lysozyme. In Case 2, cyclophosphamide had been given for rheumatoid arthritis. After a latency of 34 months 'smouldering leukaemia' developed with an atypical monocytic leukaemic cell population. In a third case, multiple myeloma and monocytic leukaemia developed synchronously. The causative role of melphalan and cyclophosphamide in the development of AML seems securely established. Despite the risk of alkylating agents in the treatment of multiple myeloma or Hodgkin's disease causing AML, they should not be replaced, as other drugs have been shown to be less beneficial. On the other hand, alkylating agents should be used with great caution in the treatment of non-malignant diseases.

Unlabelled: Gel-filtration and immunodiffusion reveal most patients with disseminated cancer excrete 100 to 1000 mg/day of urine proteins, mol wt 10,000-60,000, which are distinct from known plasma proteins and cancer-related antigens. By gel-filtration and ion-exchange chromatography, 5 novel urinary glycoproteins have been isolated which are responsible for about 1/2 the mass of the "low molecular weight proteinuria" of patients with advanced cancer: BJC1 and BJC2 (patient B.J., chronic myelocytic leukemia); JBB5 (J.B., metastatic pancreatic carcinoma); EDC1 (E.D., acute myelocytic leukemia); HNC1beta (H.N., acute monocytic leukemia). Mol wts respectively are 29,000, 22,000, 55,000, 27,000 and 33,000, and carbohydrate contents respectively 61%, 23%, 23%, 27% and 40%. Attention to date has focussed on EDC1 and HNC1beta, because their urinary excretion directly reflects the course of the neoplastic disease. EDC1 and HNC1beta possess the same protein but different carbohydrate moieties. They are antigenically related to inter-alpha trypsin inhibitor, mol wt 160,000, which is one of the 6 antiproteolytic proteins in normal human plasma. EDC1 and HNC1beta both possess antitryptic activity. Specific radioimmunoassays (RIA) to these 2 glycoproteins were developed. Normal individuals (n = 210) excreted 0.3 +/- .02 (ave. +/- SE) mg EDC1 per g creatinine. In 18 non-neoplastic diseases (n = 75), urinary EDC1 was .5 +/- .06 mg/g creatinine. In disseminated cancer of 7 types (n = 81) (breast, ovary, colon, squamous of head-neck and lung; melanoma; acute myelocytic leukemia), ave. EDC1 excretion ranged from 10 to 190 mg/g creatinine. A significant increase (P less than .05) was found in the localized stage of squamous cancer of head-neck-lung, but only after regional or distant spread in the other types. Similar results were found with HNC1beta, urinary excretion of which averaged 1/10 that of EDC1. Effective chemotherapy in 5 patients with leukemia or solid tumors caused prompt disappearance of urinary EDC1; the glyco-protein reappeared in the urine several weeks before clinical relapse., Conclusions: (i) EDC1- and HNC1beta-proteinuria is a useful indicator of some types of localized and most types of disseminated cancer; (ii) the degree of this proteinuria reflects the effectiveness of chemotherapy; (iii) the antiproteolytic property of EDC1 and HNC1beta suggests a relation between proteolysis and tumorigenesis.