More Than Just X-Rays - Imaging of Chemotherapy-induced Morphological and Functional Cardiovascular and Lung Changes After Childhood ALL and Other Cancers - a Monocentric Late Effects Study (MaximALL) (MaximALL)

"MaximALL" More Than Just X-Rays - Imaging of Chemotherapy-induced Morphological and Functional Cardiovascular and Lung Changes After Childhood ALL and Other Cancers - a Monocentric Late Effects Study (MaximALL)

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.

Study Overview

• Status: Recruiting
• Conditions: Lymphoma; Acute Lymphatic Leukemia
• Intervention / Treatment: Diagnostic test: Spirometry; Diagnostic test: DLCO measurement; Diagnostic test: Echocardioraphy; Diagnostic test: MRI; Other: Clinical parameters; Other: QOL assessment, Neuropsychological; Diagnostic test: Blood samples; Diagnostic test: MSOT

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.

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Axel Karow, PD. Dr. med.; Phone Number: 09131 8533118; Email: axel.karow@uk-erlangen.de
• Study Contact Backup: Name: Ferdinand Knieling, Prof. Dr. med.; Phone Number: 09131 8533118; Email: ferdinand.knieling@uk-erlangen.de

Study Locations

• Germany
  • Erlangen, Germany, 91054
    • Recruiting
    • Department of Pediatrics and Adolescent Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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

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 Lymphoma:

Inclusion Criteria:

• Completed therapy for lymphoma
• age >/= 3 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.)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Control Group; Healthy individuals with no previous cancer diagnosis. Volunteers will receive physical examination, standardized pulmonary function testing including spirometry and assessment of the diffusing capacity of the lung for carbon monoxide (DLCO) using a single-breath technique and MRI on a low field system (Lung and heart). Furthermore, cardiopulmonary testing (spiroergometry and echocardiography) is performed.	Diagnostic test: Spirometry; During this non-invasive test, the subject must breathe against resistance through a mouthpiece.; Diagnostic test: DLCO measurement; DLCO measurement is a non-invasive pulmonary function test for Pulmonary Diffusion Capacity.; Diagnostic test: Echocardioraphy; Echocardiography with strain-rate imaging.; Diagnostic test: MRI; LF-MRI for detection of morphological and functional changes in the lung and heart.; Other: Clinical parameters; Recording patient information (Age, Gender, Weight and height, Ethnicity, current medication, measurement of blood pressure and blood oxygen saturation.
Other: Survivors of leukemia; Survivors of treatment for acute lymphatic leukemia in childhood or adolescence. Participants will receive physical examination, standardized pulmonary function testing including spirometry and assessment of the diffusing capacity of the lung for carbon monoxide (DLCO) using a single-breath technique and MRI on a low field system (Lung and heart). Furthermore, cardiopulmonary testing (spiroergometry and echocardiography) and multispectral optoacoustic tomography (MSOT) for Peripheral artery disease (PAD) are performed. compliant data storage). In addition, venous blood samples will be taken for the analysis of molecular biomarkers.	Diagnostic test: Spirometry; During this non-invasive test, the subject must breathe against resistance through a mouthpiece.; Diagnostic test: DLCO measurement; DLCO measurement is a non-invasive pulmonary function test for Pulmonary Diffusion Capacity.; Diagnostic test: Echocardioraphy; Echocardiography with strain-rate imaging.; Diagnostic test: MRI; LF-MRI for detection of morphological and functional changes in the lung and heart.; Other: Clinical parameters; Recording patient information (Age, Gender, Weight and height, Ethnicity, current medication, measurement of blood pressure and blood oxygen saturation.; Other: QOL assessment, Neuropsychological; QoL assessment by EORTC SURV100, PPR; Diagnostic test: Blood samples; Blood samples for further molecular testing regarding epigenetic aging markers and telomere biology parameters.; Diagnostic test: MSOT; multispectral optoacoustic tomography of musculus gastrocnemius bilaterally for screening of PAD
Other: Survivors of lymphoma; Survivors of treatment for lymphoma in childhood or adolescence. Participants will receive physical examination, standardized pulmonary function testing including spirometry and assessment of the diffusing capacity of the lung for carbon monoxide (DLCO) using a single-breath technique and MRI on a low field system (Lung and heart). Furthermore, cardiopulmonary testing (spiroergometry and echocardiography) and multispectral optoacoustic tomography (MSOT) for Peripheral artery disease (PAD) are performed. compliant data storage). In addition, venous blood samples will be taken for the analysis of molecular biomarkers.	Diagnostic test: Spirometry; During this non-invasive test, the subject must breathe against resistance through a mouthpiece.; Diagnostic test: DLCO measurement; DLCO measurement is a non-invasive pulmonary function test for Pulmonary Diffusion Capacity.; Diagnostic test: Echocardioraphy; Echocardiography with strain-rate imaging.; Diagnostic test: MRI; LF-MRI for detection of morphological and functional changes in the lung and heart.; Other: Clinical parameters; Recording patient information (Age, Gender, Weight and height, Ethnicity, current medication, measurement of blood pressure and blood oxygen saturation.; Other: QOL assessment, Neuropsychological; QoL assessment by EORTC SURV100, PPR; Diagnostic test: Blood samples; Blood samples for further molecular testing regarding epigenetic aging markers and telomere biology parameters.; Diagnostic test: MSOT; multispectral optoacoustic tomography of musculus gastrocnemius bilaterally for screening of PAD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Morphological lung changes (MRI)	Morphological lung changes	Single time point
Functional lung parameters (MRI)	Ventilation match/mismatch, Perfusion match/mismatch, combined defects	Single time point
Quantitative and functional cardiovascular changes (MRI)	Quantitative and functional cardiovascular changes of the heart	Single time point

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DLCO	diffusing capacity of the lungs for carbon monoxide (absolute value and % of predicted value)	Single time point
VA	Alveolar Volume	Single time point
KCO	DLCO/VA (absolute and % of predicted value)	Single time point
VC	VC (vital capacity) in %	single time point
FEV1	FEV1 (Forced Expiratory Volume in 1 Second) in %	Single time point
VO2	Oxygen uptake (VO2)	Single time point
VO2max	peak oxygen uptake (VO2max)	Single time point
RER	Respiratory exchange ratio (RER)	Single time point
VT2	Ventilatory anaerobic threshold (VT2)	Single time point
VCO2	Carbon dioxide output (VCO2)	Single time point
HR	Heart rate (HR)	Single time point
HRR	Heart Rate Reserve (HRR)	Single time point
Breath rate at VAT	Breath rate at VAT	Single time point
BRR	Breath rate reserve (BRR)	Single time point
VE	minute ventilation (VE)	Single time point
O2 Pulse	O2 Pulse	Single time point
HRV	Heart rate variability (HRV)	Single time point
Borg Scale	Exercise capacity (Borg Scale)	Single time point
Echocardiography	Myocardial function by echocardiographic strain and strain-rate imaging	Single time point
Clinical parameters 1	Age in years	Single time point
Clinical parameters 2	Gender	Single time point
Clinical parameters 3	Weight	Single time point
Clinical parameters 4	Ethnicity	Single time point
Clinical parameters 5	Time from therapy initiation/Interval until study day	Single time point
Clinical parameters 6	Current medication*	Single time point
Clinical parameters 7	Secondary diagnoses	Single time point
Blood pressure	Blood pressure measurement	Single time point
Clinical examination	Standard clinical examination	Single time point
Questionnaire regarding psychosocial aspects	EORTC-SURV100 PPR (Posttraumatische Persönliche Reifung) Adapted Decision Regret questionnaire for childhood cancer survivors	Single time point
Blood samples 1	Presence of clonal hematopoiesis (CH)	Single time point
Blood samples 2	Type of CH-associated gene mutations (e.g. DNMT3A, TET2, DDR genes)	Single time point
Blood samples 3	Clone size / variant allele frequency (VAF)	Single time point
Blood samples 4	Epigenetic aging markers (e.g. epigenetic age acceleration measures)	Single time point
Blood samples 5	Telomere biology parameters (e.g. telomere length-related measures)	Single time point
Blood samples 6	biomarkers for long-term pulmonary dysfunction (WFDC2, TNFR1, MMP2, SPD18)	Single time point
MSOT 1	Oxygenated haemoglobin (HbO₂)	Single time point
MSOT 2	Deoxygenated haemoglobin (HHb)	Single time point
MSOT 3	Total haemoglobin (tHb)	Single time point
MSOT 4	Tissue oxygen saturation (sO₂)	Single time point
MSOT 5	MSOT signal intensity per region of interest	Single time point
MSOT 6	MSOT topogram of perfusion of the m. gastrocnemius	Single time point

Collaborators and Investigators

• Sponsor: University of Erlangen-Nürnberg Medical School

Study record dates

Study Major Dates

• Study Start (Estimated): July 14, 2026
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): October 31, 2028

Study Registration Dates

• First Submitted: July 9, 2026
• First Submitted That Met QC Criteria: July 9, 2026
• First Posted (Actual): July 15, 2026

Study Record Updates

• Last Update Posted (Actual): July 15, 2026
• Last Update Submitted That Met QC Criteria: July 9, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Hemic and Lymphatic Diseases; Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Diagnostic Techniques, Respiratory System; Respiratory Function Tests; Blood Specimen Collection; Spirometry
• Other Study ID Numbers: MaximALL; DKS 2025.17 (Other Grant/Funding Number: Deutsche Kinderkrebsstiftung); 2026-03 (Other Grant/Funding Number: Verein zur Förderung des Tumorzentrums und des CCC Erlangen-EMN der Universität Erlangen-Nürnberg e.V.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The raw, individual and identifiable patient data are protected and are not available due to data privacy laws. Further data sets are planned to be shared
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication

IPD Sharing Access Criteria

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.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No