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Non-compliance with oral chemotherapy in childhood leukaemia

BMJ 1996; 313 doi: (Published 16 November 1996) Cite this as: BMJ 1996;313:1219
  1. J S Lilleyman,
  2. L Lennard
  1. Professor Department of Paediatric Oncology, St Bartholomew's and the Royal London School of Medicine and Dentistry, St Bartholomew's Hospital, London EC1A 7BE
  2. Lecturer Department of Medicine and Pharmacology, University of Sheffield Medical School, The Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF

    An overlooked and costly cause of late relapse

    In childhood acute lymphoblastic leukaemia, complete remission is usually followed by relapse unless patients receive prolonged outpatient “maintenance” treatment based on daily oral 6-mercaptopurine and weekly methotrexate.1 When patients relapse unexpectedly some months or years after completing their planned schedule of treatment (as still occurs in 20–30% of patients in Britain), the maintenance component of treatment has probably failed for some reason.

    One contributory factor used to be insufficient doses of antimetabolites. Before 1980, four year disease free survival in Britain was less than 50%. Then a more rigid and detailed national protocol was introduced, where maintenance was more aggressively applied and attenuation of the drug dose was not left up to the individual physician. The result was an increase in toxicity accompanied by a 15–20% improvement in long term survival.2 This experience has persuaded paediatric oncologists in Britain to prescribe the maximum tolerated dose of antimetabolites and to avoid interruptions to treatment wherever possible.

    So far, so good. But the story does not end there. It is now becoming increasingly apparent that some children simply do not take the drugs they are prescribed. Based on experience with asthma,3 tuberculosis,4 cystic fibrosis,5 diabetes,6 and penicillin prophylaxis for sickle cell disease,7 we know that children often fail to follow important diets or treatment schedules. It …

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