Long term effects of chemotherapy for pediatric acute lymphoblastic leukaemia on brain morphology and neurocognitive outcome of survivors

Acute lymphoblastic leukaemia (ALL) is the most frequent cancer in childhood. Today, affected children have excellent chances of survival due to effective modern treatments. Chemotherapy is the therapy of choice for the treatment of childhood ALL. With chemotherapy about 70-80 per cent (lifetime survival rate) of the children reach a full remission. Nevertheless, chemotherapy is not free of adverse reactions. The main acute adverse side effects are, e.g. bone marrow suppression, breakdown of the immune system, toxic effects of chemotherapy on the liver, the kidneys or the lungs. Little is known about long-term effects of chemotherapy on the developing nervous system of children. Cytostatics destroy rapid-growing cells, which are tumor cells, but also healthy tissues (epithelial cells) such as hair follicles or the mucous membranes in the stomach and gut. The impact of chemotherapy on dividing cells in the brain has not been investigated. Of great interest for this study are neural stem cells in the developing brain, these are cells which have the ability to divide and build new neurons and glial cells in the brain throughout life. The generation of new nerve cells takes place in the olfactory bulbs and the hippocampus. The olfactory bulbs are crucial for smelling and the hippocampus for learning and memory. This study aims at investigating the long term effects of chemotherapy in adolescents with a morphological and neuropsychological focus. We investigate healthy adolescents with former diagnosis of ALL who were treated with chemotherapy but did not receive radiation of the brain. Comparisons are made to healthy age-matched controls. With neuroimaging methods (structural MRI) we want to explore whether chemotherapy induces persistent volume changes in the adolescent brain, especially in the bulbus olfactorius and the hippocampus. Smell tests provide functional information about changes in the quality of smelling tests and neuropsychological tests (like IQ-test) give us information of functional changes of the brain after treatment with cytostatics.

Researchers:
Thomas Hübner
Michael N. Smolka

Collaborations:
Nasreddin D. Abolmaali, OncoRay – Center for Radiation Research in Oncology,  Technische Universität Dresden, Germany
Marina Genschaft, Department of Neuropediatrics, Technische Universität Dresden, Germany
Chris Ikonomidou, Department of Neurology, University of Wisconsin-Madison, USA
Thomas Hummel, Department of Otorhinolaryngology, Technische Universität Dresden, Germany
Clemens Kirschbaum, Department of Psychology, Technische Universität Dresden, Germany