Myelodysplasia and the acute myeloid leukaemias

Abstract

The myelodysplastic syndromes are increasingly recognised clinical entities reflecting a stem cell defect that gives rise to ineffective clonal haematopoiesis. The spectrum extends from relatively indolent refractory anaemia through varying combinations of leucopoenia and thrombocytopenia to acute leukaemia. Diagnosis rests on marrow hypercellularity with dysplastic morphology, apoptosis and, often distinctive cytogenetic defects. Stratification to risk-related protocols range from occasional blood transfusions or erythropoietin through innovative options including thalidomide or amifostine to haematopoietic stem cell transplantation in selected individuals. Acute myeloid leukaemia, conceptually segregated from preleukaemia, is treated differently although accumulating cellular and molecular data favour a more integrated approach. Morphology and immunophenotyping are complemented by molecular genetics. On this basis chemotherapy alone is sufficient in defined subgroups whereas others benefit by autologous or allogeneic grafting. Attention to demonstrating minimal residual disease is the basis for more specific intervention exemplified by monoclonal antibodies or maturation-inducing agents as with retinoic acid in acute progranulocytic leukaemia.