Allopurinol in the therapy of neoplasia and blood diseases. Metabolic aspects.

The rate of nucleic acid turnover is increased in malignant tissue, and hyperuricaemia and hyperuricaciduria may occur when the condition is widespread as in the myeloproliferative disorders and reticuloses. Patients who are undergoing treatment which involves the dissolution of large amounts of malignant tissue are at risk from acute urinary obstruction. This may be either intrarenal, through the precipitation of uric acid crystals in the distal part of the nephron where the urine becomes concentrated and where acidification occurs (acute uric acid nephropathy), or postrenal, through calculi or loose aggregates of uric acid crystals. This sudden increase in the rate of uric acid production occurs in the context of a complex clinical situation and the factors responsible for the development of urinary obstruction in some patients but not in others are obscure. The amount of nucleic acid breaking down and the rate at which this occurs are important, although in the case of leukaemia the pretreatment leucocyte count and the incidence of obstructive complications are not closely correlated. The rate of de novo purine biosynthesis may be important, either because the patient is also a congenital uric acid overproducer or because it has been accelerated by drug treatment as occurs when the 2-substituted thiadiazoles are given (Seegmiller, Grayzel, and Liddle, 1959; Krakoff and Balis, 1959; Seegmiller, Grayzel, Liddle, and Wyngaarden, 1963; Krakoff, 1965). The catabolism of large amounts of tissue protein superimposed on a state of chronic metabolic acidosis with hyperlacticacidaemia due to a high level of anaerobic metabolism in the tumour tissue (Field, Block, Levin, and Rall, 1966) could cause the excretion of a persistently acid urine and favour uric acid precipitation especially in a dehydrated patient. The complication may also be more