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Recently, somatic mutations of the nucleophosmin gene (NPM1), which alter the subcellular localization of the product, have been reported in acute myeloid leukemia (AML). We analyzed the clinical significance of NPM1 mutations in comparison with cytogenetics, FLT3, NRAS, and TP53 mutations, and a partial tandem duplication of the MLL gene (MLL-TD) in 257 patients with AML. We found NPM1 mutations, including 4 novel sequence variants, in 64 of 257 (24.9%) patients.NPM1 mutations were associated with normal karyotype and with internal tandem duplication (ITD) and D835 mutations in FLT3, but not with other mutations. In 190 patients without the M3 French-American-British (FAB) subtype who were treated with the protocol of the Japan Adult Leukemia Study Group, multivariate analyses showed that the NPM1 mutation was a favorable factor for achieving complete remission but was associated with a high relapse rate. Sequential analysis using 39 paired samples obtained at diagnosis and relapse showed that NPM1 mutations were lost at relapse in 2 of the 17 patients who had NPM1 mutations at diagnosis. These results suggest that the NPM1 mutation is not necessarily an early event during leukemogenesis or that leukemia clones with NPM1 mutations are sensitive to chemotherapy.

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A case of transfusion-associated graft-versus-host disease (TA-GVHD) in a patient with non-Hodgkin's lymphoma is reported. The patient, a 67-year-old woman, was diagnosed as having diffuse, mixed type non-Hodgkin's lymphoma, at clinical stage IIIA. She was treated with combination chemotherapy and received multiple blood transfusions for anemia and thrombocytopenia. Although white cells (WBCs) were reduced in the transfused components by WBC-reduction filters, the patient developed TA-GVHD that was confirmed by skin biopsy. It is suggested that the WBC reduction attained with these filters does not prevent TA-GVHD in immunocompromised patients. It is recommended that all blood components should be irradiated before transfusion to such patients.