Poster Presenter

Effect Of Busulphan Dose Adjustment On Regimen-Related Toxicity
Zuzana Hassan, Mats Remberger, Olle Ringdén, Gunnar Öberg, Albert Békassy, Moustapha Hassan. Sweden
Sweden

Stem cell transplantation (SCT) is a curative treatment for many patients, however, regimen-related toxicity (RRT) is a major drawback. The present study includes 470 allogeneic or autologous transplanted patients from three transplantation centers in Sweden between 1987 and 2002. All patients were conditioned using busulphan-cyclophosphamide. Busulphan (Bu) pharmacokinetics were followed by measuring the area under the concentration-time curve (AUC) after the first dose and the mean Bu plasma trough levels from dose 3 through dose 16 in all patients. Busulphan doses were adjusted in 277 patients whenever appropriate. The target trough concentrations of Bu were 450-600 ng/ml and the target AUC after the first dose of Bu was 4500-5500 ng. hr/ml. Dose adjustments decreased the variation in exposure to Bu among and within the different age groups. Veno-occlusive disease (VOD), hemorrhagic cystitis and interstitial pneumonia (IP) were diagnosed in 4.0%, 2.9% and 4.3%, respectively, of patients in the dose-adjusted group compared to 19.7%, 13.5% and 15%, respectively, of patients without dose adjustment (p<0.001). These results show, that therapeutic drug monitoring and dose adjustment of Bu during myeloablative conditioning regimen decrease the occurrence of RRT.