Imaging of Chemotherapy-induced Morphological and Functional Lung Changes in Childhood ALL and HD

Study Overview
=================
Brief Summary
-----------------
With increasing cure rates of childhood cancer there is growing recognition of late effects of treatments. However, there is a lack of non-invasive and child-friendly procedures that can indicate possible late damage. This study uses morphologic and free-breathing phase-resolved functional low-field (PREFUL) magnetic resonance imaging (MRI) to identify persistent pulmonary toxicity after treatment for childhood acute lymphoblastic leukemia (ALL), Hodgkin's disease (HD) and allogeneic stem cell transplantation. Furthermore, cardiopulmonary testing is performed by means of a pulmonary function test, echocardiography with strain analysis and spiroergometry.

Detailed Description
-----------------
With increasing cure rates of childhood cancer there is growing recognition of late effects of treatments. However, there is a lack of non-invasive and child-friendly procedures that can indicate possible late damage. This study uses morphologic and free-breathing phase-resolved functional low-field (PREFUL) magnetic resonance imaging (MRI) to identify persistent pulmonary toxicity after treatment for childhood acute lymphoblastic leukemia (ALL), Hodgkin's disease (HD) and allogeneic stem cell transplantation. The examination in the new 0.55 T MRI system does not differ in procedure and especially with regard to contraindications for an MRI examination from an examination in routinely used 1.5 or 3T devices. There is no intravenous administration of contrast medium. This method has already yielded relevant results in a previous study on the frequency of lung parenchymal changes in pediatric and adolescent patients with past SARS-CoV-2 infection detected by PCR. In addition, study participants will undergo cardiopilmonary testing by spirometry, spiroergometry and echocardiography with strain analysis to assess cardiac and pulmonary performance. For the individual patient, the duration of study participation is 120 minutes. This includes approximately 30 minutes for education and consent of study participants/parents/guardians, 30 minutes for lung function test and MRI, and 30 minutes for cardiopulmonary testing. The purpose of this study is to assess early posttherapeutic changes as well as possible persistent pulmonary toxicity and change in cardiopulmonary performance.

Official Title
-----------------
iMagINg of Chemotherapy-Induced Morphological and Functional Lung Changes in Childhood Acute Lymphoblastic Leukemia and Hodgkin's Disease

Conditions
-----------------
Hodgkin Disease, Allogeneic Stem Cell Transplantation, Acute Lymphoblastic Leukemia

Intervention / Treatment
-----------------
* Diagnostic Test: Low-field magnetic resonance imaging
* Diagnostic Test: Cardiopulmonary testing
* Diagnostic Test: Pulmonary testing
* Diagnostic Test: Blood sample


Participation Criteria
=================
Eligibility Criteria
-----------------
Study arm: Early therapeutic effects Inclusion Criteria: Diagnosed acute lymphatic leukemia or Hodgkin's disease (HD) Completed induction therapy or radiotherapy 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, etc.) Study arm: Late therapeutic effects Inclusion Criteria: Diagnosed acute lymphatic leukemia or Hodgkin's disease (HD) Completed intensive therapy or radiotherapy 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, etc.) Study arm: Effects of hematopoietic stem cell transplantation Inclusion Criteria: Diagnosed acute lymphatic leukemia Completed hematopoietic stem cell transplantation 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, etc.)

Ages Eligible for Study
-----------------
Minimum Age: 5 Years
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early therapeutic effects<br>Diagnosed acute lymphatic leukemia or Hodgkin's disease (HD) and completed induction therapy or radiotherapy, from 5 years to <18 years | Diagnostic Test: Low-field magnetic resonance imaging<br>* Imaging of lung parenchyma and function by LF-MRI<br>Diagnostic Test: Cardiopulmonary testing<br>* Myocardial function (Strain-Analysis by echocardiography) and spiroergometry, capillary blood gases and lactate<br>Diagnostic Test: Pulmonary testing<br>* Lung function (VC%, FEV1%)<br>Diagnostic Test: Blood sample<br>* Standard procedures/parameters routinely available in follow-up care after oncological treatment<br>|
| Experimental: Late therapeutic effects<br>Diagnosed acute lymphatic leukemia or Hodgkin's disease (HD) and completed intensive therapy or radiotherapy, Patient in follow-up care, from 5 years to <18 years | Diagnostic Test: Low-field magnetic resonance imaging<br>* Imaging of lung parenchyma and function by LF-MRI<br>Diagnostic Test: Cardiopulmonary testing<br>* Myocardial function (Strain-Analysis by echocardiography) and spiroergometry, capillary blood gases and lactate<br>Diagnostic Test: Pulmonary testing<br>* Lung function (VC%, FEV1%)<br>Diagnostic Test: Blood sample<br>* Standard procedures/parameters routinely available in follow-up care after oncological treatment<br>|
| Experimental: Effects of hematopoietic stem cell transplantation<br>Diagnosed acute lymphatic leukemia, completed hematopoietic stem cell transplantation, from 5 years to <18 years | Diagnostic Test: Low-field magnetic resonance imaging<br>* Imaging of lung parenchyma and function by LF-MRI<br>Diagnostic Test: Cardiopulmonary testing<br>* Myocardial function (Strain-Analysis by echocardiography) and spiroergometry, capillary blood gases and lactate<br>Diagnostic Test: Pulmonary testing<br>* Lung function (VC%, FEV1%)<br>Diagnostic Test: Blood sample<br>* Standard procedures/parameters routinely available in follow-up care after oncological treatment<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morphologic lung assessment (LF-MRI) | Morphologic changes in lung parenchyma | Single time point (1 day) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional lung assessment (LF-MRI) | Change in functional lung parameters | Single time point (1 day) | 
| Cardiopulmonary testing (VO2) | Oxygen uptake | Single time point (1 day) | 
| Cardiopulmonary testing (VO2max) | Peak oxygen uptake | Single time point (1 day) | 
| Cardiopulmonary testing (RER) | Respiratory exchange ratio | Single time point (1 day) | 
| Cardiopulmonary testing (VT2) | Ventilatory anaerobic threshold | Single time point (1 day) | 
| Cardiopulmonary testing (VCO2) | Carbon dioxide output | Single time point (1 day) | 
| Cardiopulmonary testing (HR) | Heart rate | Single time point (1 day) | 
| Cardiopulmonary testing (HRR) | Heart Rate Reserve | Single time point (1 day) | 
| Cardiopulmonary testing (Breath rate at VAT) | Breath rate at VAT | Single time point (1 day) | 
| Cardiopulmonary testing (BRR) | Breath rate reserve | Single time point (1 day) | 
| Cardiopulmonary testing (VE) | Minute Ventilation | Single time point (1 day) | 
| Cardiopulmonary testing (O2-Pulse) | O2-Pulse | Single time point (1 day) | 
| Cardiopulmonary testing (HRV) | Heart rate variability | Single time point (1 day) | 
| Cardiopulmonary testing (Borg-Scale) | Exercise capacity (Borg-Scale) | Single time point (1 day) | 
| Cardiopulmonary testing (VO2) | Capillary blood gases and lactate | Single time point (1 day) | 
| Cardiopulmonary testing (Strain-Analysis) | Strain-Analysis by echocardiography | Single time point (1 day) | 
| Pulmonary test (Lung function) | Lung function (VC%, FEV1%) | Single time point (1 day) | 
| Blood sample (Blood count) | Blood Count | Single time point (1 day) | 
| Blood sample (Enterocytes) | Concentration of Enterocytes | Single time point (1 day) | 
| Blood sample (Liver enzymes) | Liver enzymes | Single time point (1 day) | 
| Blood sample (Retention parameters) | Concentration of kreatinin and urea | Single time point (1 day) | 
| Weight | Weight of the participant in kilograms | Single time point (1 day) | 
| Height | Height of the participant in meters | Single time point (1 day) |