title: High busulfan concentrations are associated with increased transplant-related mortality in allogeneic bone marrow transplant patients.
abstract: The aim of this study was to investigate the importance of busulfan concentrations for short- and long-term survival in autologous (ABMT) and allogeneic (BMT) bone marrow transplant recipients. One hundred and seventy-three patients were included in the study; 87 ABMT and 85 BMT patients. All patients received busulfan 1 mg/kg four times daily for 4 days followed by cyclophosphamide 60 mg/kg/day for 2 days. Busulfan concentrations were measured and the mean concentration calculated for each patient. There was no difference in busulfan concentrations between BMT and ABMT patients. Patients who died before day 100 had significantly higher busulfan concentrations than patients surviving beyond day 100 (719 ng/ml vs 589 ng/ml; P < 0.02). BMT patients who had busulfan concentrations in the highest quartile had significantly worse disease-free survival (DFS) and survival compared to other patients. The transplant-related mortalities (TRM) at 100 days were 29 and 14% in patients in the highest quartile and remaining patients, respectively. There was no difference in relapse incidence. High busulfan concentrations were associated with increased TRM but no difference in either survival or DFS could be found for the ABMT patients. Monitoring of busulfan concentrations is important in reducing the risk for TRM in patients undergoing bone marrow transplantation.
authors.affiliation: Department of Hematology, Huddinge University Hospital, Karolinska Institute, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Ljungman
authors.forename: M
authors.initials: M
authors.lastname: Hassan
authors.forename: A N
authors.initials: AN
authors.lastname: Békássy
authors.forename: O
authors.initials: O
authors.lastname: Ringdén
authors.forename: G
authors.initials: G
authors.lastname: Oberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000401:mortality*; D002066:Busulfan / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007223:Infant; D007938:Leukemia / Q000401:mortality / Q000628:therapy; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D016019:Survival Analysis; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D002066:Busulfan; D008727:Methotrexate