Longitudinal Investigation of Hippocampal Function and Morphology in Acute Lymphatic Leukemia (ALL) Patients Treated With Chemotherapy

Longitudinal Investigation of Hippocampal Function and Morphology in ALL Patients Treated With Chemotherapy: A Monocentric, Interdisciplinary Pilot Study

There are two regions in the adult brain that exhibit neuronal stem and progenitor cells, generating new neurons postnatally and throughout adulthood. One is the so called subventricular zone the other is the dentate gyrus of the hippocampus. Adult neurogenesis is a physiological process representing an important functional impact for certain brain areas, especially the hippocampus. The hippocampal formation plays an important role in long-term memory and spatial navigation. Inhibition of adult neurogenesis in mice by chemotherapy or radiation is followed by significant deficits in hippocampal memory functions while hippocampus-independent memory is unaffected.

Clinical trials had shown that chemotherapy and brain radiation lead to cognitive dysfunction. However, the exact mechanisms underlying this phenomenon are still unidentified.

The aim of our study is to investigate, whether the inhibition of adult neural stem cell proliferation in the hippocampus by intrathecal chemotherapy and/or cerebral radiation is responsible for treatment induced memory deficits. We will investigate patients suffering from acute lymphatic leukaemia (ALL) that receive prophylactic intrathecal chemotherapy and brain irradiation. The study represents a longitudinal investigation including a virtual "humanized" version of the morris-water-maze to test hippocampus dependent spatial memory, as well as MR-imaging for morphological (volumetry) and biochemical (spectroscopy) data.

Inclusion Criteria:

• Initial diagnosis of acute lymphatic leukaemia (ALL)
• Treatment within the German Multicenter Adult ALL (GMALL 2003) therapy study
• Age 18 to 40 years
• Eligibility for performing study procedure
• Informed consent

Exclusion Criteria:

• Neuropsychiatric disorders
• Present contraindication for MRI investigation (e.g. pacemaker)