title: Evaluation of effects of busulfan and DMA on SOS in pediatric stem cell recipients.
abstract: BACKGROUND
  Busulfan (Bu) is a DNA-alkylating agent used for myeloablative conditioning in stem cell transplantation in children and adults. While the use of intravenous rather than oral administration of Bu has reduced inter-individual variability in plasma levels, toxicity still occurs frequently after hematopoietic stem cell transplantation (HSCT). Toxicity (especially hepatotoxic effects) of intravenous (IV) Bu may be related to both Bu and/or N,N-dimethylacetamide (DMA), the solvent of Bu. In this study, we assessed the relation between the exposure of Bu and DMA with regards to the clinical outcome in children from two cohorts.
  
  
  METHODS
  In a two-centre study Bu and DMA AUC (area under the curve) were correlated in pediatric stem cell recipients to the risk of developing SOS and to the clinical outcome.
  
  
  RESULTS
  In patients receiving Bu four times per day Bu levels >1,500 µmol/L minute correlate to an increased risk of developing a SOS. In the collective cohort, summarizing data of all 53 patients of this study, neither high area under the curve (AUC) of Bu nor high AUC of DMA appears to be an independent risk factor for the development of SOS in children.
  
  
  CONCLUSIONS
  In this study neither Bu nor DMA was observed as an independent risk factor for the development of SOS. To identify subgroups (e.g., infants), in which Bu or DMA might be risk factors for the induction of SOS, larger cohorts have to be evaluated.
authors.affiliation: Department of Pediatric Hematology and Oncology, University Childrens Hospital Münster, Muenster, Germany.
authors.forename: Kornelius
authors.initials: K
authors.lastname: Kerl
authors.forename: Christian
authors.initials: C
authors.lastname: Diestelhorst
authors.forename: Imke
authors.initials: I
authors.lastname: Bartelink
authors.forename: Jaap
authors.initials: J
authors.lastname: Boelens
authors.forename: Mirjam N
authors.initials: MN
authors.lastname: Trame
authors.forename: Joachim
authors.initials: J
authors.lastname: Boos
authors.forename: Georg
authors.initials: G
authors.lastname: Hempel
mesh_terms: D000081:Acetamides / Q000009:adverse effects*; D000293:Adolescent; D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols; D002066:Busulfan / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003451:Cryoprotective Agents / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D019337:Hematologic Neoplasms / Q000150:complications* / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced* / Q000473:pathology; D006801:Humans; D007223:Infant; D008297:Male; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D000081:Acetamides; D018906:Antineoplastic Agents, Alkylating; D003451:Cryoprotective Agents; D002066:Busulfan; C013959:dimethylacetamide
keywords: BMT; Busulfan; DMA; SOS