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Evaluation of effects of busulfan and DMA on SOS in pediatric stem cell recipients
Author(s) -
Kerl Kornelius,
Diestelhorst Christian,
Bartelink Imke,
Boelens Jaap,
Trame Mirjam N.,
Boos Joachim,
Hempel Georg
Publication year - 2014
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.24827
Subject(s) - medicine , busulfan , oncology , stem cell , toxicity , hematopoietic stem cell transplantation , transplantation , cohort , biology , genetics
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. Result 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. Conclusion 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. Pediatr Blood Cancer 2014;61:306–311. © 2013 Wiley Periodicals, Inc.