Preengraftment C-Reactive Protein Predicts Infection Risk and Nonrelapse Mortality in Pediatric Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

J. McNeer, R. Duerst, D. Jacobsohn, A. Rademaker, M. Kletzel
2009 Biology of Blood and Marrow Transplantation  
Busulfan (Bu) is often used as part of the conditioning regimen for pediatric patients undergoing allogeneic (allo) stem cell transplantation (SCT). Current pediatric dosing recommendations are based on age and weight, with children 4 years of age or younger receiving a higher every 6 hour (q6h) dose (1 mg/kg/dose) than children older than 4 (0.8 mg/kg/dose) (Wall et al, Blood, 2000a). Twice-daily (q12h) dosing is an attractive alternative to q6h dosing, requiring less nursing time and less
more » ... ssing of the patient's central venous catheter. Twice-daily dosing is not currently in wide use, however, as IV Bu has a narrow therapeutic range and there is no published data confirming that q12h pharmacokinetics (PK) are comparable to q6h PK. From April 2003 to November 2007, 42 pediatric patients (age # 21 yrs) with malignant (n 5 16) and nonmalignant (n 5 26) conditions underwent alloSCT (23 unrelated cord blood, 3 related cord blood, 8 matched unrelated donor peripheral blood or marrow, 8 matched family donor peripheral blood or marrow) with preparative regimens including IV Bu q12h x 8 doses (3.2mg/ kg/day, 4 mg/kg/day if age # 4 yrs) and subsequent IV Bu PK analysis. Patients received phenytoin/fosphenytoin seizure prophylaxis and FK506/MMF GVHD prophylaxis. PK samples were obtained at hr 1, 2, 3, 5, 6, 7 and 8 after start of 1st dose. Bu levels were measured by a GC-MS method on heparinized plasma. PK results were compared to PK data from pediatric q6h dosing historical controls derived from the literature (Booth et al, J Clin Pharmacol, 2007) and from the database of the Toxicology Laboratory of the Hospital of the University of Pennsylvania. IV Bu q12h clearance (Cl) and volume of distribution (Vd) point estimates (n 5 38) were similar to published PK results for q6h dosing in the pediatric population (q6 vs. q12h Cl [L/h]: 4.04 vs 4.46, respectively; q6 vs. q12h Vd [L]: 12.8 vs. 13.3, respectively). There was no statistically significant difference between the steady-state concentrations (Css) (n 5 35) achieved with q12h dosing when compared to q6h patients wellmatched for age and weight (n 5 90) in the University of Pennsylvania database (737 6 239 ng/mL vs. 673 6 164 ng/mL, p 5 0.25; q6h vs. q12h, respectively). No patients developed VOD. This data suggests that IV Bu q12h in children has a PK profile similar to q6h dosing and is safe, while providing the benefits of reduced nursing time and less accessing of the patient's central venous catheter.
doi:10.1016/j.bbmt.2008.12.231 fatcat:o27c3wjfdbduzm6strnnk6x2mi