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

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.

Study Overview

• Status: Unknown
• Conditions: Acute Lymphatic Leukemia

• Study Type: Observational
• Enrollment (Anticipated): 10

Contacts and Locations

Study Locations

• Germany
  • Dresden, Germany, 01307
    • Recruiting
    • Dresden University of Technology University Hospital
    • Contact: Moritz Brandt, MD; Phone Number: 18507 +49-351-458; Email: moritz.brandt@uniklinikum-dresden.de
    • Contact: Kalina Brandt; Phone Number: 2610 +49-351-458; Email: kalina.brandt@uniklinikum-dresden.de
    • Sub-Investigator: Kalina Brandt
    • Sub-Investigator: Moritz Brandt, MD
    • Sub-Investigator: Martin Bornhaeuser, MD
    • Principal Investigator: Alexander Storch, MD
    • Sub-Investigator: Annett Werner, PhD
    • Sub-Investigator: Markus Schaich, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Consecutive patients of the Department of Internal Medicine at the Dresden University of Technology hospital, who are initially diagnosed of acute lymphatic leukemia (ALL) and included into the GMALL 2003 chemotherapy study. All treatment procedures and outcome measurements of the GMALL 2003 study (most importantly also the safety outcome measures) are regularly performed in the sub population of the present sub study. Inclusion and exclusion criteria are given below.

Description

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)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Patient with ALL under chemotherapy; 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?

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

Collaborators and Investigators

• Sponsor: Technische Universität Dresden
• Collaborators: Martin-Luther-Universität Halle-Wittenberg
• Investigators: Principal Investigator: Alexander Storch, MD, Technische Universität Dresden

Study record dates

Study Major Dates

• Study Start: February 1, 2010

Study Registration Dates

• First Submitted: March 31, 2010
• First Submitted That Met QC Criteria: April 26, 2010
• First Posted (Estimate): April 27, 2010

Study Record Updates

• Last Update Posted (Estimate): April 27, 2010
• Last Update Submitted That Met QC Criteria: April 26, 2010
• Last Verified: April 1, 2010

More Information

Terms related to this study

• Keywords: ALL; Hippocampus; Chemotherapy; GMALL 2003
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Leukemia, Lymphoid
• Other Study ID Numbers: EK153052009