Acute Lymphatic Leukemia, Lymphoma
Conditions
Brief summary
In this study, we investigate the cardiopulmonary health of survivors who underwent cancer treatment for acute lymphoblastic leukemia (ALL) or lymphoma during childhood, compared with healthy controls. Modern imaging techniques (MRI, MSOT, and echocardiography) as well as questionnaires assessing cardiopulmonary and mental health are used.
Detailed description
Survivors of childhood cancer have a high risk of developing late effects regarding different organ systems even years after treatment. Our preliminary data show that a high number of our study participants who have received oncological treatment for ALL or Hodgkin's disease, develop severe ventilation and/or perfusion disorders/defects that can be detected on MRI of the lungs. These changes are mainly observed in participants with a greater interval to the oncological treatment and we could find a significant correlation between ventilation- and perfusion defects and the timespan after diagnosis. In spiroergometry, our patient group showed reduced aerobic capacity (ViO2 max), regardless of the time of follow-up. Echocardiography including strain analysis resulted in suspicious findings. The aim of our follow-up project is to validate these results in a larger patient population and to extend the investigations of long-term follow up after oncological disease/treatment in childhood and adolescence. We are planning to conduct a multicenter study with participants (who received oncological treatment in childhood or adolescence and are now undergoing long-term-follow-up care (\> 5 years after treatment,). Therefore, we will examine morphological und functional lung changes by low field strength MRI and spiroergometry. We plan to investigate cardiac changes by echocardiography with strain analysis and ECG. Additionally, we would like to use multispectral optoacoustic tomography (MSOT) screening for muscle atrophy due to peripheral artery disease (PAD) as another modern imaging procedure for early detection of vascular changes.
Interventions
QoL assessment by EORTC SURV100, PPR
During this non-invasive test, the subject must breathe against resistance through a mouthpiece.
DLCO measurement is a non-invasive pulmonary function test for Pulmonary Diffusion Capacity.
Echocardiography with strain-rate imaging.
LF-MRI for detection of morphological and functional changes in the lung and heart.
Recording patient information (Age, Gender, Weight and height, Ethnicity, current medication, measurement of blood pressure and blood oxygen saturation.
Blood samples for further molecular testing regarding epigenetic aging markers and telomere biology parameters.
multispectral optoacoustic tomography of musculus gastrocnemius bilaterally for screening of PAD
Sponsors
Study design
Eligibility
Inclusion criteria
Control Group: Inclusion Criteria: * no cancer diagnosis * no lung diseases * no vascular diseases * No subjective reduction in physical performance * age \>/= 18 years
Exclusion criteria
* Pregnancy, Lactation * Known pleural or pericardial effusion * Critical condition (requiring respiratory support, ventilation, oxygen, shock, symptomatic heart failure) * Marked thoracic deformities/malformations * Previous lung surgery * Injuries that do not allow physical stress diagnostics * Rejection of MRI imaging * General contraindications for MRI examinations (e.g. electrical implants such as cardiac pacemakers or perfusion pumps, copper IUD etc.) Survivors of ALL: Inclusion Criteria: * Completed therapy for ALL * age \>/= 3 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Morphological lung changes (MRI) | Single time point | Morphological lung changes |
| Functional lung parameters (MRI) | Single time point | Ventilation match/mismatch, Perfusion match/mismatch, combined defects |
| Quantitative and functional cardiovascular changes (MRI) | Single time point | Quantitative and functional cardiovascular changes of the heart |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| DLCO | Single time point | diffusing capacity of the lungs for carbon monoxide (absolute value and % of predicted value) |
| VA | Single time point | Alveolar Volume |
| KCO | Single time point | DLCO/VA (absolute and % of predicted value) |
| VC | single time point | VC (vital capacity) in % |
| FEV1 | Single time point | FEV1 (Forced Expiratory Volume in 1 Second) in % |
| VO2 | Single time point | Oxygen uptake (VO2) |
| VO2max | Single time point | peak oxygen uptake (VO2max) |
| RER | Single time point | Respiratory exchange ratio (RER) |
| VT2 | Single time point | Ventilatory anaerobic threshold (VT2) |
| VCO2 | Single time point | Carbon dioxide output (VCO2) |
| HR | Single time point | Heart rate (HR) |
| HRR | Single time point | Heart Rate Reserve (HRR) |
| Breath rate at VAT | Single time point | Breath rate at VAT |
| BRR | Single time point | Breath rate reserve (BRR) |
| VE | Single time point | minute ventilation (VE) |
| O2 Pulse | Single time point | O2 Pulse |
| HRV | Single time point | Heart rate variability (HRV) |
| Borg Scale | Single time point | Exercise capacity (Borg Scale) |
| Echocardiography | Single time point | Myocardial function by echocardiographic strain and strain-rate imaging |
| Clinical parameters 1 | Single time point | Age in years |
| Clinical parameters 2 | Single time point | Gender |
| Clinical parameters 3 | Single time point | Weight |
| Clinical parameters 4 | Single time point | Ethnicity |
| Clinical parameters 5 | Single time point | Time from therapy initiation/Interval until study day |
| Clinical parameters 6 | Single time point | Current medication\* |
| Clinical parameters 7 | Single time point | Secondary diagnoses |
| Blood pressure | Single time point | Blood pressure measurement |
| Clinical examination | Single time point | Standard clinical examination |
| Questionnaire regarding psychosocial aspects | Single time point | EORTC-SURV100 PPR (Posttraumatische Persönliche Reifung) Adapted Decision Regret questionnaire for childhood cancer survivors |
| Blood samples 1 | Single time point | Presence of clonal hematopoiesis (CH) |
| Blood samples 2 | Single time point | Type of CH-associated gene mutations (e.g. DNMT3A, TET2, DDR genes) |
| Blood samples 3 | Single time point | Clone size / variant allele frequency (VAF) |
| Blood samples 4 | Single time point | Epigenetic aging markers (e.g. epigenetic age acceleration measures) |
| Blood samples 5 | Single time point | Telomere biology parameters (e.g. telomere length-related measures) |
| Blood samples 6 | Single time point | biomarkers for long-term pulmonary dysfunction (WFDC2, TNFR1, MMP2, SPD18) |
| MSOT 1 | Single time point | Oxygenated haemoglobin (HbO₂) |
| MSOT 2 | Single time point | Deoxygenated haemoglobin (HHb) |
| MSOT 3 | Single time point | Total haemoglobin (tHb) |
| MSOT 4 | Single time point | Tissue oxygen saturation (sO₂) |
| MSOT 5 | Single time point | MSOT signal intensity per region of interest |
| MSOT 6 | Single time point | MSOT topogram of perfusion of the m. gastrocnemius |
Countries
Germany