5 Therapy and prognostic factors in adult acute lymphoblastic leukaemia

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Summary

In acute lymphoblastic leukaemia (ALL) substantial progress has been achieved within the last few years. Complete remission rates up to 95% can now be achieved in children and 70–85% in adults; disease free survival rates are 70 and 30% respectively. To improve results further high dose treatment has been included, particularly to overcome drug resistance and to reach cytostatic levels in the sanctuary sites, such as the central nervous system. High dose cytarabine in combination with other cytostatic drugs, preferentially anthracyclines, seems to be of benefit for high risk adult ALL patients. High dose methotrexate, mostly explored in childhood ALL, is now also included in a variety of combinations in the treatment of adult ALL, but its effectiveness remains to be established. Substantial progress has been achieved in adult T-ALL and B-ALL with survival rates of 40–50%.

The optimal form and duration of maintenance therapy in adult ALL is not yet clear but general omission of maintenance leaves patients with an inferior outcome. Which subgroups of adult ALL require maintenance and in what form still requires investigation.

In recent adult ALL trials with intensive chemotherapy similar prognostic factors for disease free survival have emerged. Of adverse influence are delayed time to reach CR (more than 4/5 weeks), a high initial white blood cell count, higher age (above 50 or 60 years), and probably the immunological subtypes pre-T-ALL, pre-B-ALL, My+-ALL; of very adverse influence in elderly patients is the karyotype t(9;22) or the corresponding BCR/ABL gene rearrangement. High risk adult ALL patients with one or more of these adverse factors are candidates for allogeneic or autologous bone marrow transplantation in first remission. Whether all adult ALL patients are candidates for BMT in first CR is currently being explored in large prospective randomized trials.

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