Clonal evolution of aplastic anaemia to myelodysplasia acute myeloid leukaemia and paroxysmal nocturnal haemoglobinuria

Aplastic anaemia (AA) is a non-malignant haemopoietic disorder characterise d by peripheral blood pancytopenia and a hypocellular bone marrow. Successf ul management of acquired AA including treatment with immunosuppressive age nts, mainly antithymocyte globulin (ATG) and cyclosporin or allogeneic haem opoietic stem cell transplantation, has resulted in long-term survival of m any patients. The later evolution of complicating clonal disorders such as paroxysmal nocturnal haemoglobinuria, myelodysplasia and acute myeloid leuk aemia in patients treated with immunosuppressive therapy may be a manifesta tion of the natural history of the aplasia, the development of which may or may not be increased by immunosuppressive therapy. A persistent, profound deficiency and/or defect in the stem cell compartment, despite haematologic al recovery after immunosuppressive therapy, may create an unstable situati on which predisposes to later clonal disorders. A review of the progression of AA to clonal disorders is now outlined.