Infectious side effects of cancer treatment in children. Clinical and genetic aspects

PhD ceremony: Ms. E.M. te Poele, 14.30 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Infectious side effects of cancer treatment in children. Clinical and genetic aspects

Promotor(s): prof. E.S.J.M de Bont, prof. W.A. Kamps

Faculty: Medical Sciences

Chemotherapy has significantly improved the survival of children with cancer. One of the side effects of chemotherapy is the inhibited production of white blood cells. This effect predisposes for infections and infectious complications. Therefore, fever during neutropenia (lack of a specific type of white blood cells) is treated with intravenous antibiotics. The first part of this thesis deals with clinical issues. We examined the possibilities for a better risk assessment of fever during neutropenia to prevent overtreatment of patients with a low risk for bacterial infections. This cost-efficient approach may contribute to a better quality of life.

Subsequently, we studied the number of infectious deaths during the ALL-9 protocol (treatment for acute lymphoblastic leukemia (ALL) in children). We found an increase in the number of infectious deaths compared to previous protocols. This is most probably caused by repeated, prolonged treatment with the drug Dexamethasone in ALL-9. Furthermore, the use of Pegfilgrastim was evaluated. This medicine may be administered to reduce chemotherapy induced neutropenia. Pegfilgrastim is only registered for use in adults, but also seems to be safe for children. Lastly, we studied the mortality of non-elective ICU admissions in children with cancer. One of the conclusions of this study is that the survival of these children increased significantly. The second part of this thesis concerns several studies of genetic variants and the risk of developing ALL and (fever during) neutropenia. It was concluded that particular genetic variants that are associated with atopy have an inverse association with ALL.