ORIGINAL ARTICLE Long-term salivary function after conditioning with busulfan, fractionated or single-dose TBI K. Garming-Legert 1,2 , M. Remberger 3 , O. Ringde´n 3 , M. Hassan 4 , G. Dahllo¨f 2 1 Division of Oral and Maxillofacial Surgery, Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden; 2 Division of Orthodontics and Pediatric Dentistry, Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden; 3 Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Huddinge, Sweden; 4 Experimental Cancer Medicine, Laboratory Medicine, Karolinska University Hospital, Huddinge, Sweden OBJECTIVES: Does conditioning with fractionated total body irradiation (fTBI) or busulfan (Bu) causes less sali- vary dysfunction compared with single dose (sTBI) after hematopoietic stem cell transplantation (HSCT). PATIENTS AND METHODS: A total of 74 adolescents below 13 years of age received allogeneic HSCT and conditioning with either: sTBI, fTBI or Bu. The unstimu- lated (USSR) and stimulated (SSSR) whole salivary secretion rates were measured at 15 years of age. RESULTS: Irrespective of conditioning type, there were no significant differences in USSR or SSSR between groups. Girls had a significantly lower SSSR, 0.7 ± 0.3 ml per min compared with 1.1 ± 0.4 ml per min in boys (P < 0.001). A significant correlation between age at HSCT and SSSR at 15 years of age (P = 0.02) in children conditioned with sTBI was found as well as an inverse correlation between the plasma area under curve (AUC) of Bu and SSSR. In the multivariate model, only female sex was significantly correlated with low SSSR at 15 years of age (OR 3.93, 95% CI 1.21–12.79; P = 0.021). CONCLUSION: No differences in long-term whole sali- vary function after HSCT in adolescents receiving con- ditioning with sTBI, fTBI or Bu were found. Total systemic exposure to Bu was negatively correlated with stimulated salivary secretion. Oral Diseases (2011) doi: 10.1111/j.1601-0825.2011.01821.x Keywords: busulfan; cancer; children; oral; pharmacokinetics; saliva Introduction Hematopoietic stem cell transplantation (HSCT) is increasingly used to treat a variety of malignant and non-malignant disorders in children (Ringde´n and Le Blanc, 2005). HSCT is the transplantation of multipo- tent hematopoietic stem cells derived from bone mar- row, peripheral blood, or umbilical cord blood from a donor and given to the patient. Allogeneic HSC donors must have a tissue human leucocyte antigen (HLA) type that is compatible with the patient. Even if there is a good match, the patient will require immunosuppressive medications to mitigate graft-versus-host disease (GVHD). Immediately before transplantation, the patient is given chemotherapy or irradiation or both together with immunosuppressive therapy. After several weeks of growth in the bone marrow, expansion of HSC and their progeny is sufficient to normalize the blood cell counts and reinitiate the immune system (Garthon and Ringde´ n, 1997). As a result of advances in treatment, almost 80% of children and adolescents diagnosed with cancer become long-term survivors. It is also evident that damage to organs and tissues caused by chemotherapy and radia- tion therapy may not become clinically evident for many years after treatment. In a study of 10 397 childhood cancer survivors, 62% had at least one chronic health condition and 28% had a severe or life-threatening condition. The cumulative incidence of a chronic health condition was 73%, 30 years after cancer diagnosis (Oeffinger et al, 2006). Several factors may contribute to the delayed effects after HSCT including the primary disease process itself, the transplant immune biology or the pretransplantation regimens (Ringde´ n et al, 1996; Ringde´n and Le Blanc, 2005). Delayed effects are found in 78% of childhood cancer survivors treated with HSCT (Ness et al, 2005). Symptoms such as cataracts, renal dysfunction, diabetes mellitus, growth hormone deficiency, osteoporosis, delayed puberty, developmental delay and muscle weak- ness are highly specific for children who received HSCT. Correspondence: Karin Garming-Legert, Division of Oral and Max- illofacial Surgery, Department of Dental Medicine, Box SE- 4064, SE-141 04, Huddinge, Sweden. Tel: +46 8 58583950, Fax: +46 8 7743875, E-mail: karin.garming.legert@ki.se Received 28 February 2011; Revised 8 May 2011; accepted 22 May 2011 Oral Diseases (2011) doi:10.1111/j.1601-0825.2011.01821.x Ó 2011 John Wiley & Sons A/S All rights reserved www.wiley.com