In most patients with large granular lymphocyte (LGL) leukemia, the disease appears to progress slowly if at all, and no therapy is generally required. We present a patient with CD3+ CD8+ CD16+ LGL leukemia, who showed a benign clinical course for more than 7 months without therapy, but subsequently developed aggressive disease. A feature of considerable interest was the transformation into an acute or aggressive form in this patient affected preferentially the liver and spleen, and was not associated with the hematologic features of the circulating leukemic cells, as assessed by morphologic, phenotypic and molecular analyses. The patient was treated with combination chemotherapy; this resulted in clinical remission with persistence of the abnormal clone in the peripheral blood. The mechanism responsible for the preferential organ involvement and the process of progression from the chronic to the acute form in this case are discussed from the viewpoint of a lymphoproliferative disorder.

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