Immune monitoring in the context of hematopoietic cell transplantation in children

Abstract

In this thesis the potential of immune monitoring before and after stem cell transplantation in pediatric patients is described. As each patient is unique, it is often unknown how the immune system will respond to medication after stem cell transplantation. In addition, risk factors and markers correlating to disease status and outcome are lacking. Immune monitoring can provide insights into immune cell behavior at different stages during therapy.

Part 1 of this thesis focusses on immune monitoring in children with high-risk neuroblastoma. Certain immune cells (T-cells) have impaired function after stem cell transplantation. While other cells, that suppress the immune system (Tregs), function normally and increase in blood after medication (IL-2 and GM-CSF). These new findings justify standardized immune monitoring in NBL patients before and during therapy to gather data on the association of the immune status of a patient and clinical outcome.

Part 2 describes effects of immune modulation of malignant and non-malignant pediatric patients receiving an allogeneic stem cell transplantation. Immune monitoring after stem cell transplantation shows that patients with CD4+ T cell reconstitution have lower risk of GvHD-associated death. Chemo-naivety (no chemotherapy before stem cell transplantation) is a risk factor for the development of autoimmune cytopenia and lung complications. In addition, acute GvHD and/or serotherapy are risk factors for autoimmune cytopenia, while adenovirus reactivation is a risk factor for lung complications. An increase in immunoglobulins in blood preceded autoimmune cytopenia.