Individualized therapeutics in allogeneic stem cell transplantation

Brink, M.H. ten (2014)

Doctoral Thesis

Pharmacotherapy plays an essential role in an allogeneic hematopoietic stem cell transplantation (allo-HSCT) procedure. Busulfan and treosulfan are two alkylating agents often applied in the conditioning regimen administered prior to the allo-HSCT. Finding the right balance between efficacious conditioning and toxicity remains the challenge for both agents. A majore One of the major complications after allo-HSCT is Acute graft-versus-host disease (aGvHD). When patients are diagnosed with grade 2 or higher aGvHD, systemic treatment with high-dose glucocorticoids is started as first line treatment. However, only half of the patients respond adequately to this therapy and also in other diseases non-responsiveness to glucocorticoids has been observed. Optimization of current drug therapies in allo-HSCT holds the potential to improve the outcome and safety. The goal of this thesis is to optimize busulfan- and treosulfan-based conditioning regimens and acute GvHD treatment with glucocorticoids by applying pharmacokinetic and pharmacogenetic profiling. Studies are performed in adults and pediatric patients.

• Glucocorticoids
• Treosulfan
• Busulfan
• Pediatrics
• Pharmacogenetics
• Pharmacokinetics
• Allogeneic stem cell transplantation

• All authors: Brink, M.H. ten
• Supervisor: Guchelaar, H.J.
• Co-supervisor: Lankester, A.C.; Zwaveling, J.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine (LUMC), Leiden University
• Date: 2014-09-03
• ISBN (print): 9789492026019