SUMMARY The in vivo effect of various cytotoxic drugs and cranial irradiation on neutrophil chemotaxis was tested in 62 children with acute lymphoblastic leukaemia and in 10 patients with other malignant disease. Cranial radiotherapy had a transient adverse effect on neutrophil chemotaxis after completion of the course which was most marked in children. Methotrexate (MTX) and 6-mercaptopurine (6-MP) alone and in combination had a variable effect on chemotaxis, which was most marked nine days after the end of the course. The effect of 6-MP was clearly dose-related, but continuous therapy (75 mg/M2 day) had the greatest inhibitory effect of all the regimens tested.The in vitro effect was studied in 48 leukaemics and in 85 controls (adults and children); all the patients with leukaemia had been off treatment for at least six months. No difference was found between the effects of drugs tested on control or leukaemic cells. The greatest inhibitory effect was found with vinblastine, adriamycin, 6-MP, and vincristine, all of which were closely dose-dependent. MTX, prednisolone, and asparaginase had no effect on chemotaxis when tested in this way.Previous studies have shown that cranial radiotherapy and antileukaemic drugs adversely affect neutrophil function in acute lymphoblastic leukaemia in remission.'-3 A significant correlation between impaired neutiophil chemotaxis and the incidence and severity of bacterial infection confirmed the importance of this function.2 Furthermore, an increased morbidity and mortality from infection in the post-irradiation period has been reported45 with a significant reduction in infection when the dose of concurrent cytotoxic therapy was reduced.4With the known association of increased remission deaths with more intensive antileukaemic treatment,6 we decided to study the effect of commonly used cytotoxic drugs and cranial radiation on neutrophil chemotaxis. Also, in view of the increasing preference for combination chemotherapy in a maximum dose, often limited only by severe neutropenia, we considered it was necessary to know whether different combinations of drugs, dosage, or pulsed or continuous administration had any effect on neutrophil chemotaxis.
Material and methods
IN VIVO EFFECTStudies were carried out in 14 patients who had received cranial radiotherapy: eight children with Accepted for publication 16 June 1980 leukaemia had each received 2400 rad in 12 fractions over 21 days, and six patients (four adults and two children) with cerebral tumours had received 3000-3500 rad in 20-25 fractions over four to five weeks. Chemotactic studies were done before, duting, and after completion of radiotherapy. Concurrent chemotherapy consisted of a small daily dose of 6-MP (25 mg/M2) in the former and of dexamethasone (4-8 mg daily) in the latter.The effect of MTX and 6-MP in different regimens was tested in 29 individuals. The regimens consisted of simultaneous (studies 1 and 2) or sequential (study 3) administration of MTX and 6-MP, and continuous 6-MP with weekly MTX (study 4). In n...