HIGH BUSULFAN CONCENTRATIONS ARE ASSOCIATED WITH INCREASED TRANSPLANT-RELATED MORTALITY IN ALLOGENEIC BONE-MARROW TRANSPLANT PATIENTS

The aim of this study was to investigate the importance of busulfan co ncentrations for short-and long-term survival in autologous (ABMT) and allogeneic (BMT) bone marrow transplant recipients. One hundred and s eventy-three patients were included in the study; 87 ABMT and 85 BMT p atients. All patients received busulfan 1 mg/kg four times daily for 4 days followed by cyclophosphamide 60 mg/kg/day for 2 days. Busulfan c oncentrations were measured and the mean concentration calculated for each patient. There was no difference in busulfan concentrations betwe en BMT and ABMT patients. Patients who died before day 100 had signifi cantly higher busulfan concentrations than patients surviving beyond d ay 100 (719 ng/ml vs 589 ng/ml; P < 0.02). BMT patients who had busulf an concentrations in the highest quartile had significantly worse dise ase-free survival (DFS) and survival compared to other patients. The t ransplant-related mortalities (TRM) at 100 days were 29 and 14% in pat ients in the highest quartile and remaining patients, respectively. Th ere was no difference in relapse incidence. High busulfan concentratio ns were associated with increased TRM but no difference in either surv ival or DFS could be found for the ABMT patients. Monitoring of busulf an concentrations is important in reducing the risk for TRM in patient s undergoing bone marrow transplantation.