Neoplasms

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Immune System Diseases

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Ataxia Telangiectasia

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Lymphosarcoma

Spinocerebellar Ataxia

Sarah Elitzur, MD

Naomi Litichever, PhD

Ataxia telangiectasia (A-T) is a multisystem disease with diverse manifestations, including progressive neurodegeneration, immunodeficiency, respiratory disease, and genomic instability. One of the most important features of A-T is the increased predisposition to cancer, especially to lymphoid malignancies. Patients with A-T are generally excluded from collaborative clinical trials, their treatment outcomes and toxicity profiles have rarely been reported, and little is currently known concerning the treatment intensity required to provide a reasonable balance between efficacy and toxicity. The aims of this study are to build a large international de-identified database of children with A-T treated for leukemia and lymphoma, to investigate epidemiology and outcome of treatment, toxicity profiles and risk factors which impact outcome, in order to eventually enable the generation of data-based treatment recommendations for this population.

Ataxia telangiectasia (A-T) is a multisystem disease with diverse manifestations, including progressive neurodegeneration, immunodeficiency, respiratory disease, and genomic instability. A-T is caused by biallelic mutations in the ATM gene, a major activator of the cellular response to DNA double strand breaks. One of the most important features of A-T is the increased predisposition to cancer. Lymphoid malignancies represent the majority of cancers. The treatment of cancer in children with A-T is extremely challenging, due to severe co-morbidities and a significantly increased risk of cancer therapy-related toxicities. Patients with A-T are generally excluded from collaborative clinical trials, their treatment outcomes and toxicity profiles have rarely been reported, and little is currently known concerning the treatment intensity required to provide a reasonable balance between efficacy and toxicity. The optimal treatment approach is controversial; some advocate treatment by standard chemotherapeutic protocols, while others advise initial protocol modifications with chemotherapy dose reductions. Due to the rarity of this disorder, there is an unmet need for an international collaboration for data collection concerning treatment, toxicity and outcome in children with cancer and A-T. Data will be collected from patient files, including patient characteristics and history, AT manifestations, malignancy characteristics, treatment, chemotherapy doses, treatment response, toxicity and outcome.

The aims of the study are to build a large international de-identified database of children with A-T treated for leukemia and lymphoma, to investigate epidemiology and outcome of treatment, toxicity profiles and risk factors which impact outcome, in order to eventually enable the generation of data-based treatment recommendations for this population.

This study will not involve the use of specimens or participant contact. All the data required have already been collected during the treatment of the participants, and is available in patient records.

Treatment of Leukemia and Lymphoma in Children With Ataxia Telangiectasia

Treatment of Leukemia and Lymphoma in Children With Ataxia Telangiectasia- A Retrospective Study

Assess 5-year cumulative incidence of leukemia/lymphoma relapse

Assess 2-year cumulative incidence of treatment-related mortality

Assess 5-year cumulative incidence of second malignancies

Determine cause of death and timing of death in relation to specific elements of leukemia/lymphoma therapy (by questionnaire)

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Israeli Society for Pediatric Hematology-Oncology

International BFM Study Group

Rabin Medical Center

Infections

Digestive System Diseases

Communicable Diseases

Liver Diseases

Disease Susceptibility

Gastrointestinal Diseases

All Drugs and Chemicals

Hematinics

Antibodies

Immunoglobulins

Immunoglobulin G

Liver Extracts

Immunoglobulins, Intravenous

A-T patients aged 2 to 45 years with and without immunoglobulin G Substitution

* bioelectrical impedance Analysis
* blood draw
* transient elastography (FibroScan)
* ataxia score
* Five-Times-Sit-to-Stand Test

Electrophysical measurement that allows to determine the exact composition of single body compartments by producing a magnetic field and detecting the potential difference through the body

bioelectrical impedance analysis

Blood samples are taken from sober patients

blood draw

FibroScan is a noninvasive tool to measure liver stiffness as an indication of fatty liver and liver fibrosis using ultrasound

transient elastography (FibroScan)

Klockgether ataxia score ranges from 0 to 35 points in which 0 means no symptoms and 35 stands for final stage of disease. It includes seven ataxia associated symptoms: dysarthria, intention tremor, ataxia of gait, stance, dysdiadochokinesia, upper limb and lower limb

ataxia score

The test measures the complete time which is necessary for an individual to stand up and sit down on a chair five times in series

Five-Times-Sit-to-Stand Test

Sandra Woelke, Dr.

Stefan Zielen, Prof. Dr.

Sandra Wölke, Dr.

Ataxia telangiectasia (A-T) is a rare devastating human recessive disorder characterized by progressive cerebellar ataxia, immunodeficiency, chromosomal instability and cancer susceptibility. The immunodeficiency is expressed by recurring infections. It's characterised by decreased lymphocytes data as well as lack of immunglobulin A, immunglobulin G subclasses and specific antibodies against pneumococcus. Aim of the present clinical trial is to investigate frequency-, intensity- and duration of the infections as well as changes oft immune status, dimension of liver disease and tumor risk in patients with A-T, with and without immunoglobulin G substitution therapy. Transient elastography (FibroScan) will be performed in order to measure liver stiffness as an indication of fatty liver and liver fibrosis. A bioelectrical impedance analysis (BIA) is conducted to investigate the exact body composition. Ataxia Score is determined to define neurological problems. Every subject receives a diary to compile symptoms of infection.

Ataxia teleangiectasia (A-T) is a rare devastating human recessive disorder characterized by progressive cerebellar ataxia, immunodeficiency, chromosomal instability and cancer susceptibility. The immunodeficiency is expressed by recurring infections. It's characterised by decreased lymphocytes data as well as lack of immunglobulin A, immunglobulin G subclasses and specific antibodies against pneumococcus as shown in many trials. Additionally the patients suffer from a fatty liver with increased transaminases and have the risk for a cirrhosis of the liver and a hepatocellular carcinoma. It's known that the dimension of the liver disease affects susceptibility to infection. Nevertheless there are only a few studies treating this problem.

Despite the proof of the immunodeficiency polyvalent immunoglobulins (IgG) are not given regularly. Own observations show that in spite of the treatment with immunoglobulins the progression of a chronic destructive lung disease with development of bronchiectasis hardly can prohibited.

Up to now it isn't cleared if a substitution therapy with immunoglobulins reduces the susceptibility to infection. Therefore the aim oft the present clinical trial ist to explore frequency-, intensity, and duration oft the infections as well as changes oft the immune status, measure of liver disease and tumor risk in patients with A-T, with and without immunoglobulin therapy. The study includes five visits, which are performed in all A-T patients. Visit 1, 3, 5 are realized in the context of annual follow ups:

* To evaluate weight and length of all subjects
* To analyze the exact structure of single body compartments such as the lean mass, the water compartment or the fat compartment using bioelectrical impedance analysis
* To define the neurological status by ataxia score
* To get a detailed immune status, vaccination status and liver values as well as special tumor markers in blood
* To check the lung function using spirometry
* To measure liver stiffness using transient elastography (FibroScan)
* To compile any symptoms of infection by diary
* To investigate the ataxia status and physical condition by means of the Five-Times-Sit-to-Stand Test

Visit 2 and 4 are additionally conducted as study visits:

* To get a detailed immune status in blood
* To check the lung function using spirometry

Susceptibility to Infections, Tumor Risk and Liver Disease in Patients With Ataxia Telangiectasia

Susceptibility to Infections, Tumor Risk and Liver Disease in Patients With Ataxia Telangiectasia With and Without Substitution of Immunoglobulin G: a Prospective Observational Study

Evaluation of frequency, severity and intensity of infections in A-T patients with and without immunoglobulin G substitution

Evaluation of the degree of liver disease measured by liver enzymes and structural changes by transient elastography (Fibroscan) in A-T patients

Evaluation of tumor markers in A-T patients

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Treatment of Leukemia and Lymphoma in Children With Ataxia Telangiectasia	NCT04037189	Ataxia Telangie... Leukemia Lymphoma		0 Years - 21 Years	Rabin Medical Center
Treatment of Leukemia and Lymphoma in Children With Ataxia Telangiectasia	NCT04037189	Ataxia Telangie... Leukemia Lymphoma		0 Years - 21 Years	Rabin Medical Center
Susceptibility to Infections, Tumor Risk and Liver Disease in Patients With Ataxia Telangiectasia	NCT03357978	Ataxia Telangie...	bioelectrical i... blood draw transient elast... ataxia score Five-Times-Sit-...	2 Years - 45 Years	Johann Wolfgang Goethe University Hospital

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