[Individualized cancer treatment. Illustrated by acute lymphoblastic leukemia in children]

The intensity of treatment in children with acute lymphoblastic leukaemia has conventionally been based on risk group stratification, which reflected the patient's age and white cell count at diagnosis, as well as the immunophenotype and presence of certain high risk chromosomal aberrations. Identification of the latter has often failed, owing to the very selective demands for lymphoblast culture. Nevertheless, the risk-adapted and very intensive antileukaemic therapy has been a success, with cure rates as high as 75-80 per cent. However, a large fraction of these patients are overtreated. A more individualiZed tailoring of the therapy is expected to be available through: 1) A series of new and more direct techniques to reveal chromosomal aberrations; 2) exploration of the in vitro drug sensitivity of the malignant clone; 3) detailed monitoring of the minimal residual disease down to the level of one leukaemic cell in 10,000-100,000 normal bone marrow cells; 4) therapeutic drug monitoring and individual dose adjustments; and 5) mapping of the individual patient's risk of serious or even life-threatening side effects. It is likely that these approaches would allow a reduction in the treatment intensity for most patients, thereby reducing the risk of serious toxicity, and concomitantly improve identification of those patients for whom standard therapy is likely to fail and who are thus candidates for stem cell transplantion or experimental therapy in first remission.