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

Study Overview
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Brief Summary
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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.

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

Conditions
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Acute Lymphatic Leukemia

Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patient with ALL under chemotherapy<br>This group consists of patients with initial diagnosis of acute lymphatic leukemia (ALL), who are enrolled into the GMALL 2003 chemotherapy study. There is no change of the initial GMALL 2003 treatment protocol for the present study. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hippocampal function measured with virtual water maze test | The hippocampal function will by studies in a longitudinal manner and thus we plan to measure the water maze test performance at several time points (time frames) of the study. | day 0 | 
| Hippocampal function measured with virtual water maze test | The hippocampal function will by studies in a longitudinal manner and thus we plan to measure the water maze test performance at several time points (time frames) of the study. | day 9 | 
| Hippocampal function measured with virtual water maze test | The hippocampal function will by studies in a longitudinal manner and thus we plan to measure the water maze test performance at several time points (time frames) of the study. | day 16 | 
| Hippocampal function measured with virtual water maze test | The hippocampal function will by studies in a longitudinal manner and thus we plan to measure the water maze test performance at several time points (time frames) of the study. | day 52 | 
| Hippocampal function measured with virtual water maze test | The hippocampal function will by studies in a longitudinal manner and thus we plan to measure the water maze test performance at several time points (time frames) of the study. | day 70 | 
| Hippocampal function measured with virtual water maze test | The hippocampal function will by studies in a longitudinal manner and thus we plan to measure the water maze test performance at several time points (time frames) of the study. | week 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hippocampal morphology measured by MRI |  | day 0 | 
| Hippocampal morphology measured by MRI |  | day 29 | 
| Hippocampal morphology measured by MRI |  | day 70 | 
| Hippocampal morphology measured by MRI |  | week 36 | 
| Peripheral blood cell count | Since we investigate a subpopulation of the GMALL 2003 chemotherapy study, all safety measures of the GMALL 2003 study are performed in the population of the present study. Peripheral blood cell counts for estimating the chemotherapy toxicity according to WHO criteria and the minimal residual disease activity. | day 0 | 
| Peripheral blood cell count | Since we investigate a subpopulation of the GMALL 2003 chemotherapy study, all safety measures of the GMALL 2003 study are performed in the population of the present study. Peripheral blood cell counts for estimating the chemotherapy toxicity according to WHO criteria and the minimal residual disease activity. | day 26 | 
| Peripheral blood cell count | Since we investigate a subpopulation of the GMALL 2003 chemotherapy study, all safety measures of the GMALL 2003 study are performed in the population of the present study. Peripheral blood cell counts for estimating the chemotherapy toxicity according to WHO criteria and the minimal residual disease activity. | day 46 | 
| Peripheral blood cell count | Since we investigate a subpopulation of the GMALL 2003 chemotherapy study, all safety measures of the GMALL 2003 study are performed in the population of the present study. Peripheral blood cell counts for estimating the chemotherapy toxicity according to WHO criteria and the minimal residual disease activity. | day 71 | 
| Peripheral blood cell count | Since we investigate a subpopulation of the GMALL 2003 chemotherapy study, all safety measures of the GMALL 2003 study are performed in the population of the present study. Peripheral blood cell counts for estimating the chemotherapy toxicity according to WHO criteria and the minimal residual disease activity. | week 16 | 
| Peripheral blood cell count | Since we investigate a subpopulation of the GMALL 2003 chemotherapy study, all safety measures of the GMALL 2003 study are performed in the population of the present study. Peripheral blood cell counts for estimating the chemotherapy toxicity according to WHO criteria and the minimal residual disease activity. | week 22 | 
| Peripheral blood cell count | Since we investigate a subpopulation of the GMALL 2003 chemotherapy study, all safety measures of the GMALL 2003 study are performed in the population of the present study. Peripheral blood cell counts for estimating the chemotherapy toxicity according to WHO criteria and the minimal residual disease activity. | week 30 | 
| Peripheral blood cell count | Since we investigate a subpopulation of the GMALL 2003 chemotherapy study, all safety measures of the GMALL 2003 study are performed in the population of the present study. Peripheral blood cell counts for estimating the chemotherapy toxicity according to WHO criteria and the minimal residual disease activity. | week 41 | 
| Peripheral blood count | Since we investigate a subpopulation of the GMALL 2003 chemotherapy study, all safety measures of the GMALL 2003 study are performed in the population of the present study. Peripheral blood cell counts for estimating the chemotherapy toxicity according to WHO criteria and the minimal residual disease activity. | week 52 | 
| Bone marrow examination | Since we investigate a subpopulation of the GMALL 2003 chemotherapy study, all safety measures of the GMALL 2003 study are performed in the population of the present study. Bone marrow examination is investigated to extimate minimal residual disease activity and chemotherapy toxicity according to WHO criteria. | day 0 | 
| Bone marrow examination | Since we investigate a subpopulation of the GMALL 2003 chemotherapy study, all safety measures of the GMALL 2003 study are performed in the population of the present study. Bone marrow examination is investigated to extimate minimal residual disease activity and chemotherapy toxicity according to WHO criteria. | day 26 | 
| Bone marrow examination | Since we investigate a subpopulation of the GMALL 2003 chemotherapy study, all safety measures of the GMALL 2003 study are performed in the population of the present study. Bone marrow examination is investigated to extimate minimal residual disease activity and chemotherapy toxicity according to WHO criteria. | day 46 | 
| Bone marrow examination | Since we investigate a subpopulation of the GMALL 2003 chemotherapy study, all safety measures of the GMALL 2003 study are performed in the population of the present study. Bone marrow examination is investigated to extimate minimal residual disease activity and chemotherapy toxicity according to WHO criteria. | day 71 | 
| Bone marrow examination | Since we investigate a subpopulation of the GMALL 2003 chemotherapy study, all safety measures of the GMALL 2003 study are performed in the population of the present study. Bone marrow examination is investigated to extimate minimal residual disease activity and chemotherapy toxicity according to WHO criteria. | week 16 | 
| Bone marrow examination | Since we investigate a subpopulation of the GMALL 2003 chemotherapy study, all safety measures of the GMALL 2003 study are performed in the population of the present study. Bone marrow examination is investigated to extimate minimal residual disease activity and chemotherapy toxicity according to WHO criteria. | week 22 | 
| Bone marrow examination | Since we investigate a subpopulation of the GMALL 2003 chemotherapy study, all safety measures of the GMALL 2003 study are performed in the population of the present study. Bone marrow examination is investigated to extimate minimal residual disease activity and chemotherapy toxicity according to WHO criteria. | week 30 | 
| Bone marrow examination | Since we investigate a subpopulation of the GMALL 2003 chemotherapy study, all safety measures of the GMALL 2003 study are performed in the population of the present study. Bone marrow examination is investigated to extimate minimal residual disease activity and chemotherapy toxicity according to WHO criteria. | week 41 | 
| Bone marrow examination | Since we investigate a subpopulation of the GMALL 2003 chemotherapy study, all safety measures of the GMALL 2003 study are performed in the population of the present study. Bone marrow examination is investigated to extimate minimal residual disease activity and chemotherapy toxicity according to WHO criteria. | week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALL, GMALL 2003, Chemotherapy, Hippocampus