Torsades de pointes upon fluconazole administration in a patient with acute myeloblastic leukemia.

Prolonged QT syndrome often causes torsades de pointes (Tdp), a potentially lethal arrhythmia. A 55-year-old woman with M4Eo who was receiving consolidation chemotherapy had an episode of prolonged QT and Tdp following fluconazole (FCZ) administration. Intravenous supplementation of magnesium sulfate and multiple attempts at electrocardioversion led to recovery from the arrhythmia. FCZ appears to contribute to the development of QT prolongation, in particular with low concentrations of serum potassium or magnesium. Although mechanisms of Tdp development in patients with QT prolongation remain to be determined, it is possible that FCZ administration leads to manifestation of Tdp. Special cautions should be exercised upon the emergence of QT prolongation following FCZ administration.

[Allergic reaction against an emulsifier, HCO-60, contained in multamin and enocitabine].

We report two cases of an allergic reaction to HCO-60, which is used as an emulsifien for Multamin and enocitabine. A 55-year-old woman with M 4 Eo developed a high fever, urticaria and erythema after induction chemotherapy. After stopping the administration of Multamin, her fever and eruptions subsided. A 51-year-old woman with L 2 developed erythema and hypotension 30 minutes after the third administration of Multamin. When the patient was given enocitabine, she developed anaphylactic shock. During chemotherapy in patients with leukemia, it is important to distinguish the allergic reaction against Multamin-containing HCO-60 from infection and allergies to other drugs.

Decreased susceptibility of leukemic cells with PIG-A mutation to natural killer cells in vitro.

The cloning of the PIG-A gene has facilitated the unraveling of the complex pathophysiology of paroxysmal nocturnal hemoglobinuria (PNH). Of current major concern is the mechanism by which a PNH clone expands. Many reports have suggested that an immune mechanism operates to cause bone marrow failure in some patients with PNH, aplastic anemia, and myelodysplastic syndromes. Because blood cells of PNH phenotype are often found in patients with these marrow diseases, one hypothesis is that the PNH clone escapes immune attack, producing a survival advantage by immunoselection. To test this hypothesis, we examined the sensitivity of blood cells, with or without PIG-A mutations, to killing by natural killer (NK) cells, using 51Cr-release assay in vitro. To both peripheral blood and cultured NK cells, PIG-A mutant cells prepared from myeloid and lymphoid leukemic cell lines were less susceptible than their control counterparts (reverted from the mutant cells by transfection with a PIG-A cDNA). NK activity was completely abolished with concanamycin A and by calcium chelation, indicating that killing was perforin-dependent. There were no differences in major histocompatibility (MHC) class I expression or sensitivity to either purified perforin or to interleukin-2-activated NK cells between PIG-A mutant and control cells. From these results, we infer that PIG-A mutant cells lack molecules needed for NK activation or to trigger perforin-mediated killing. Our experiments suggest that PIG-A mutations confer a relative survival advantage to a PNH clone, contributing to selective expansion of these cells in the setting of marrow injury by cytotoxic lymphocytes.