THERAPY ASSOCIATED LEUKEMIA

A dose related risk of acute leukaemia, myelodysplasia and other cancers is seen in patients treated with certain drugs, particularly alkylating agents, and radiotherapy either alone or in combination. Treatment associated acute myeloid leukaemia (tAML) and myelodysplasia have biological and clinical features in common and are distinct from the corresponding de-novo disorders. tAML generally occurs between 2-11 years from administration of chemo/radiotherapy with few cases thereafter. Patients may present with myelodysplasia and severe cytopenia with abnormalities in all cell lines or as an acute leukaemia which may be difficult to classify because of multi-lineage involvement. Clonal cytogenetic abnormalities usually including either loss or interstitial deletion of the long arm of chromosomes 5 or 7 are frequently identified. Critical regions deleted in all patients with these lesions have been localised at 5q23-32 and 7q22-31; regions carrying the genes for several haemopoietic growth factors, receptors and oncogenes. The prognosis of patients with tAML is poor with low remission rates and a median survival of 6 months. Complex karyotypes or lesions of chromosomes 5 or 7 seen in the majority of cases are associated with a particularly poor outlook. The risks of this most serious complication of therapy should be weighed carefully against possible benefits.