Acute myeloid leukemia appearing in two patients after prolonged continuous chlorambucil treatment for Wegener's granulomatosis.

Two patients with Wegener's granulomatosis have been treated with chlorambucil and prednisolone continuosly for 3 and 5 years, respectively. This treatment was effective in controlling the disease, but bone marrow toxicity with severe pancytopenia developed in both cases. Both patients died from thrombocytopenia with haemorrhagic pericarditis. In one case, the diagnosis of acute myeloid leukaemia was established from the appearance of myeloblasts in the peripheral blood and from characteristic bone marrow morphology. In the other case this diagnosis was strongly suspected on the basis of the bone marrow morphology alone. It is proposed that this development of acute leukaemia in two patients with a primary non-neoplastic disease may result from a direct carcinogenic action of chlorambucil in humans.