Establishing a target exposure for once-daily intravenous busulfan given with fludarabine and thymoglobulin before allogeneic transplantation.
Biol Blood Marrow Transplant
; 19(9): 1381-6, 2013 Sep.
Article
in En
| MEDLINE
| ID: mdl-23871781
ABSTRACT
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 µM.min [corrected] 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 µM.min [corrected] were at increased risk for acute GVHD grade II-IV (hazard ratio [HR], 2.30; 95% confidence interval [CI], 1.19 to 4.49; P = .014). Those in the highest and lowest Bu exposure quartiles (daily AUC <3814 µM.min and >4993 µM.min) [corrected] 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% CI, 1.09 to 2.99; P = .021) and overall survival (HR, 1.94; 95% CI, 1.12 to 3.37; P = .018). Bu exposures between 4440 and 4993 µM/min were accompanied by the lowest risk of both nonrelapse mortality and acute GVHD.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Vidarabine
/
Busulfan
/
Antineoplastic Combined Chemotherapy Protocols
/
Hematopoietic Stem Cell Transplantation
/
Hematologic Neoplasms
/
Antilymphocyte Serum
Type of study:
Observational_studies
/
Risk_factors_studies
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Biol Blood Marrow Transplant
Journal subject:
HEMATOLOGIA
/
TRANSPLANTE
Year:
2013
Type:
Article
Affiliation country:
Canada