PK/PD of corticosteroids in graft-versus-host disease after hematopoietic cell transplantation in children

One of the biggest obstacles in hematopoietic cell transplantation (HCT) remains the devel-opment of graft-versus-host disease (GVHD), which occurs in approximately 40% of stem cell recipients. First-line treatment to either prevent or treat GVHD is high dose systemic cor-ticosteroids. However, the incidence of the development of GVHD in children receiving corti-costeroids as prophylactic treatment is still high. Besides, only a minority of the patients de-veloping GVHD responds adequately to corticosteroid treatment, often with lifelong therapy and reduced quality of life. Overall mortality after developing GVHD is around 30%. In current clinical practice, corticosteroid dosing is highly empirical and might result in very variable exposure levels in children. We hypothesize that precision dosing of corticosteroids, to reach an optimal exposure in every individual patient, will increase response rates in pediatric HCT. A pharmacokinetic/pharmacodynamic (PK/PD) relationship of corticosteroids has been sug-gested in other diseases where exposure to corticosteroids is associated with clinical out-comes. To date, this has not yet been investigated in the setting of GVHD. As a first step to optimize therapy for GVHD, we will study the PK/PD relationship of prednisolone in pediatric patients. If such a relationship exists, optimal dosing strategies can be developed.

Contact
Julia Möhlmann