Therapeutic drug monitoring is essential for intravenous busulfan therapy in pediatric hematopoietic stem cell recipients HSCT is a therapeutic form used worldwide for the treatment of malignant and non-malignant disorders. Today, HSCT is considered to be the treatment of choice for an increasing number of metabolic and genetic disorders in pediatric patients. Despite the increased need for HSCT, still TRM because of toxicity, infections, and GvHD are the major limiting factors (1, 2). Busulfan is a bifunctional alkylating agent developed in the early 1950s for the treatment of chronic myelogenous leukemia (CML). Busulfan was introduced as a competing chemotherapeutic drug to replace TBI for myeloablation in HSCT (3, 4). Busulfan is increasingly used in numerous conditioning protocols for HSCT to prevent TBI-associated late effects including growth retardation, cataract, endocrinological malfunc- tion in children and infants (5–7). Oral busulfan is administered usually as 1 mg/kg · 4 for four days or 2 mg/kg · 2 for four days (8); moreover, some centers have reported the use of 4 mg/kg once daily for four days (9, 10). Until recently, the only formulation of busulfan available was oral. The oral administration was associated with high inter- and intra-individual variability in plasma exposure. Fatal treatment outcome owing to high variability in busulfan kinetics in combination with a narrow therapeutic window was reported. The high interindividual variability was reported to be due to several factors including age, underlying disease, liver status, GSH, GST, and bioavailability (11, 12). Mala¨r R, Sjo¨o¨ F, Rentsch K, Hassan M, Gu¨ngo¨r T. Therapeutic drug monitoring is essential for intravenous busulfan therapy in pediatric hematopoietic stem cell recipients. Pediatr Transplantation 2011: 15: 580–588. Ó 2011 John Wiley & Sons A/S. Abstract: Busulfan is widely used for myeloablative conditioning in HSCT. Intravenous busulfan has been introduced to reduce interindi- vidual variability in plasma levels especially in pediatric patients. TDM of intravenous busulfan was performed in 34 pediatric HSCT patients with malignant (n = 9) and non-malignant (n = 25) diseases (50% of patients <three yr) in a single-center analysis (2006–2009). Intravenous busulfan was administered twice daily in a four-h infusion according to recommended weight-based doses. Busulfan drug levels were measured, and pharmacokinetic analysis was performed. The targeted busulfan exposure was aimed to range between AUC of 9000–12 000 ng/mL/h. In 23/34 patients (68%), the busulfan dose had to be adjusted at least once. In 16/23 patients (70%), the dose had to be increased in a range of 7 to 33%, while in 7/23 patients (30%), the dose had to be decreased by 7–20%. The need of dose adjustment was not related to weight, age, or underlying disease. Seven out of 34 patients (21%) <20 months expe- rienced VOD despite that their total AUCs were within the target AUC. TDM of intravenous busulfan is essential to increase the efficacy and safety of busulfan-based conditioning protocols in pediatric HSCT recipients. Reta Malär 1 , Fredrik Sjçç 2 , Katharina Rentsch 1 , Moustapha Hassan 2,3 and Tayfun Güngçr 1 1 Pediatric BMT Center, Zürich University Hospital for Children, Zürich, Switzerland, 2 Department of Laboratory Medicine, Experimental Cancer Medicine (ECM), Karolinska Institutet, Stockholm, Sweden, 3 Clinical Research Centre, Karolinska University Hospital-Huddinge, Stockholm, Sweden Key words: busulfan – therapeutic drug monitoring – pharmacokinetics – stem cell transplantation – paediatric Moustapha Hassan, Experimental Cancer Medicine (ECM), Department of Laboratory Medicine, Karolinska University Hospital-Huddinge, 141 86 Stockholm, Sweden Tel.: +46-8-58583862 Fax: +46-8-58583800 E-mail: moustapha.hassan@ki.se Accepted for publication 23 May 2011 Abbreviations: aGVHD, acute graft vs. host disease; AUC, areas under the curve; DMA, dimethylacetamide; GSH, glutathione; GST, glutathione-S-transferase; HSCT, hema- topoietic stem cell transplantation; MDS, myelodysplastic syndrome; RIC, reduced intensity conditioning; SCID, se- vere combined immunodeficiency; SOS, sinusoidal obstruction syndrome; TBI, total body irradiation; TDM, therapeutic drug monitoring; TRM, transplant-related mortality; VOD, veno-occlusive disease. Pediatr Transplantation 2011: 15: 580–588 Ó 2011 John Wiley & Sons A/S. Pediatric Transplantation DOI: 10.1111/j.1399-3046.2011.01529.x 580