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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Early therapeutic effects | Experimental | Diagnosed acute lymphatic leukemia or Hodgkin's disease (HD) and completed induction therapy or radiotherapy, from 5 years to <18 years |
|
| Late therapeutic effects | Experimental | 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 |
|
| Effects of hematopoietic stem cell transplantation | Experimental | Diagnosed acute lymphatic leukemia, completed hematopoietic stem cell transplantation, from 5 years to <18 years |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Low-field magnetic resonance imaging | Diagnostic Test | Imaging of lung parenchyma and function by LF-MRI |
|
| Measure | Description | Time Frame |
|---|---|---|
| Morphologic lung assessment (LF-MRI) | Morphologic changes in lung parenchyma | Single time point (1 day) |
| Measure | Description | Time Frame |
|---|---|---|
| Functional lung assessment (LF-MRI) | Change in functional lung parameters | Single time point (1 day) |
| Cardiopulmonary testing (VO2) | Oxygen uptake |
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Study arm: "Early therapeutic effects"
Inclusion Criteria:
Exclusion Criteria:
Study arm: "Late therapeutic effects"
Inclusion Criteria:
Exclusion Criteria:
Study arm: "Effects of hematopoietic stem cell transplantation"
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Axel Karow, MD | Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen | Principal Investigator |
| Ferdinand Knieling, MD | Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen | Principal Investigator |
| Rafael Heiß, MD | Institute of Radiology, University Hospital Erlangen | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Pediatrics and Adolescent Medicine | Erlangen | Bavaria | 91054 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32461035 | Background | Erdmann F, Frederiksen LE, Bonaventure A, Mader L, Hasle H, Robison LL, Winther JF. Childhood cancer: Survival, treatment modalities, late effects and improvements over time. Cancer Epidemiol. 2021 Apr;71(Pt B):101733. doi: 10.1016/j.canep.2020.101733. Epub 2020 May 24. | |
| 25696854 | Background | Silverman LB. Balancing cure and long-term risks in acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program. 2014 Dec 5;2014(1):190-7. doi: 10.1182/asheducation-2014.1.190. Epub 2014 Nov 18. |
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Beginning 9 months and ending 36 months following article publication.
The data sets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request as follows:
Individual participant data will not be available Study Protocol and Statistical Analysis Plan will be available The data will be available beginning 9 months and ending 36 months following article publication.
The data will be available to researchers who provide a methodologically sound proposal.
The data will be available for individual participant data meta-analysis, only. Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in our University's data warehouse but without investigator support other than deposited metadata. Information regarding submitting proposals and accessing data may be found at https://www.uk-erlangen.de.
Restrictions may apply due to patient privacy and the General Data Protection Regulation.
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 11, 2024 | Dec 11, 2024 |
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| Cardiopulmonary testing | Diagnostic Test | Myocardial function (Strain-Analysis by echocardiography) and spiroergometry, capillary blood gases and lactate |
|
| Pulmonary testing | Diagnostic Test | Lung function (VC%, FEV1%) |
|
| Blood sample | Diagnostic Test | Standard procedures/parameters routinely available in follow-up care after oncological treatment |
|
| 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) |
| 31931503 | Background | Gebauer J, Baust K, Bardi E, Grabow D, Stein A, van der Pal HJ, Calaminus G, Langer T. Guidelines for Long-Term Follow-Up after Childhood Cancer: Practical Implications for the Daily Work. Oncol Res Treat. 2020;43(3):61-69. doi: 10.1159/000504200. Epub 2020 Jan 13. |
| 40488780 | Derived | Huber F, Schoeffl I, Mueller N, Dierl A, Wild EM, Naumann-Bartsch N, Karow A, Knieling F, Woelfle J, Dittrich S, Anderheiden F. What about the heart - pediatric ALL survivors show cardiopulmonary limitations in the MinimALL Study. Eur J Pediatr. 2025 Jun 9;184(7):406. doi: 10.1007/s00431-025-06243-0. |
| Prot_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Dec 11, 2024 | Dec 11, 2024 | SAP_003.pdf |
| ID | Term |
|---|---|
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D006689 | Hodgkin Disease |
| ID | Term |
|---|---|
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D008223 | Lymphoma |
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| ID | Term |
|---|---|
| D005080 | Exercise Test |
| D001800 | Blood Specimen Collection |
| ID | Term |
|---|---|
| D006334 | Heart Function Tests |
| D003935 | Diagnostic Techniques, Cardiovascular |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D012129 | Respiratory Function Tests |
| D003948 | Diagnostic Techniques, Respiratory System |
| D016552 | Ergometry |
| D008919 | Investigative Techniques |
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
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