Individualized therapeutics in allogeneic stem cell transplantation

Abstract

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.