期刊
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
卷 19, 期 9, 页码 1381-1386出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bbmt.2013.07.002
关键词
Busulfan; Exposure; Pharmacokinetics
资金
- Otsuka Pharma
A combination of fludarabine (Flu) and daily i.v. busulfan (Bu) is well tolerated and effective in patients undergoing allogeneic hematopoietic stem cell transplantation. Although there is some evidence that Bu exposures exceeding 6000 mu M/min may lead to excessive toxicity, there is little information on the effect of exposures below this level on outcomes. We studied Bu exposure, as measured by area under the concentration-time curve (AUC), in 158 patients with various hematologic malignancies in an attempt to identify an optimal range for targeted therapy. The preparative chemotherapy regimen comprised Flu 50 mg/m(2) on days -6 to -2 and i.v. Bu 3.2 mg/kg on days -5 to -2 inclusive. Graft-versus-host disease (GVHD) prophylaxis included methotrexate, cyclosporin A, and antithymocyte globulin. Patients with Bu exposures below the median AUC of 4439 mu M/min were at increased risk for acute GVHD grade II-IV (hazard ratio [HR], 2.30; 95% confidence interval [Cl], 1.19 to 4.49; P = .014). Those in the highest and lowest Bu exposure quartiles (daily AUC <3814 mu M/min and >4993 mu M/min) had an increased risk of nonrelapse mortality (subdistribution HR, 3.32; 95% CI, 1.46 to 7.54; P = .004), as well as worse disease-free survival (HR, 1.81; 95% Cl, 1.09 to 2.99; P = .021) and overall survival (HR, 1.94; 95% Cl, 1.12 to 3.37; P = .018). Bu exposures between 4440 and 4993 mu M/min were accompanied by the lowest risk of both nonrelapse mortality and acute GVHD. (C) 2013 American Society for Blood and Marrow Transplantation.
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