iMagINg of Chemotherapy-Induced Morphological and Functional Lung Changes in Childhood Acute Lymphoblastic Leukemia and Hodgkin's Disease
Phase: NA
Conditions: Acute Lymphoblastic Leukemia, Hodgkin Disease, Allogeneic Stem Cell Transplantation
Sponsor: University of Erlangen-Nürnberg Medical School

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Study protocol 
 
 
 
“MinimALL“ 
 
iMagINg of chemotherapy-Induced Morphological and functional lung changes in 
childhood Acute Lymphoblastic Leukemia and Hodgkin`s disease 
 
 
Trial Short Title 
MinimALL 
Trial Full Title 
iMagINg 
of 
chemotherapy-Induced 
Morphological 
and 
functional 
lung 
changes 
in 
childhood 
Acute 
Lymphoblastic Leukemia and Hodgkin`s 
disease 
 
Funding 
Internal 
Trial Principle Investigator 
Dr. med. A. Karow 
PD Dr. med. F. Knieling 
Statistical Analysis Plan Authors 
Dr. med. A. Karow 
PD Dr. med. F. Knieling 
Dr. med. A. Dierl 
Document Version 
1.8 
Document Version Date 
11.12.2024 
NCT-Number 
06093334 
 
 
 

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1. Table of content 
 
1. Table of content ................................................................................................... 2 
2. Study title, version number, version date ............................................................. 3 
3. Project summary .................................................................................................. 4 
4. Responsibilities .................................................................................................... 5 
5. Scientific background ........................................................................................... 7 
6. Study aims ........................................................................................................... 8 
7. Target variables ................................................................................................... 9 
8. Study design ...................................................................................................... 11 
9. Study population ................................................................................................ 13 
10. 
Study procedures ............................................................................................ 15 
11. 
Benefit-risk assessment .................................................................................. 17 
12. 
Biometry.......................................................................................................... 21 
13. 
Data management and data protection ........................................................... 22 
14. 
Handling of biomaterial ................................................................................... 23 
15. 
Insurance for partcipants ................................................................................ 23 
16. 
Signature ........................................................................................................ 23 
 
 
 

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2. Study title, version number, version date 
 
Study title 
iMagINg of chemotherapy-Induced Morphological and functional lung changes in 
childhood Acute Lymphoblastic Leukemia and Hodgkin`s disease 
 
Version 
Version 1.8 
 
Version date 
11.12.2024 
 
Protokollversionen 
Date 
Version 
Status 
Changes 
08.11.2022 
1.0 
Draft 
 
10.11.2023 
1.1 
Draft 
Inlusion of HSCT patients 
25.01.2023 
1.2 
Final 
Inclusion of 
cardiopulmonary testing 
16.02.2023 
1.3 
 
Formal revisions 
according to 
Ethics 
Committee 
 
20.02.2023 
1.4 
Additional formal 
revisions 
according to 
Ethics 
Committee 
 
30.03.2023 
1.5 
Substantive 
revisions 
according to 
Ethics 
Committee 
 
27.04.2023 
1.6 
Amendment 
Inclusion of patients with 
Hodgkin`s disease 
11.08.2023 
1.7 
Amendment 
Complementation of 
echocardiography and 
strain analysis 
Addition of people 
conducting the study 
11.12.2024 
1.8 
Addition of 
missing 
information 
Addition of the missing 
NCT Number on the 
cover page 
 
 
 

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3. Project 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.  
 
 
 
 

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4. Responsibilities 
 
Leitung der Studie  
 
Dr. med. Axel Karow 
PD Dr. med. Ferdinand Knieling 
Kinder- und Jugendklinik 
Universitätsklinikum Erlangen 
Loschgestr. 15 
91054 Erlangen 
Tel. 09131 8533118 
Email: axel.karow@uk-erlangen.de  
Email: ferdinand.knieling@uk-erlangen.de   
 
 
PD Dr. Rafael Heiß 
Radiologisches Institut 
Maximiliansplatz 2 
91054 Erlangen 
Tel.: 09131 85-36065 
Email: rafael.heiss@uk-erlangen.de 
 
 
 
Durchführung der Studie 
 
Dr. med. Alexander Dierl 
Kinder- und Jugendklinik 
Universitätsklinikum Erlangen 
Loschgestr. 15 
91054 Erlangen 
Tel. 09131 8533118 
Email: alexander.dierl@uk-erlangen.de 
 
 
Maximilian Hinsen 
Radiologisches Institut 
Maximiliansplatz 2 
91054 Erlangen 
Tel.: 09131 85-36065 
Email: maximilian.hinsen@uk-erlangen.de 
 
 
 

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Kooperationspartner 
 
Prof. Dr. med. Michael Uder 
Direktor Radiologisches Institut 
Maximiliansplatz 2 
91054 Erlangen 
Tel.: 09131 85-36065 
Email: michael.uder@uk-erlangen.de 
 
 
PD Dr. med. Dr. rer. biol. hum. Isabelle Schöffl 
Kinderkardiologie  
Universitätsklinikum Erlangen 
Loschgestr. 15 
91054 Erlangen 
Tel. 09131 8533750 
E-Mail: isabelle.schoeffl@uk-erlangen.de 
 
 
Funding 
Internal 
 
 

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5. Scientific background 
Currently, overall cure rates of therapy for childhood acute lymphoblastic leukemia (ALL) and 
Hodgkin`s disease (HD) exceed 80% [1]. Apart from the development of supportive measures 
and novel targeted therapies, this success is still based largely on the optimized and risk-
adapted dosing and scheduling of conventional chemotherapeutic agents and addition of 
radiotherapy in patients with HD in case of suboptimal response. Even though, contemporary 
systemic and local treatment regimens are less intensive than previous therapies, they are still 
associated with diverse general and specific, acute and chronic organ toxicities such as cardiac 
dysfunction, osteonecrosis, neurocognitive impairment, and second malignant neoplasms [2]. 
With increasing cure rates has come growing recognition of such adverse late effects of 
treatment and a number of guidelines for long-term follow-up (LTFU) after childhood cancer 
therapy have been proposed [3]. During treatment and aftercare, however, only crude orienting 
investigations assessing organ function are foreseen by these recommendations and apart 
from physical examinations and laboratory analyses, echocardiography remains the only 
functional imaging measure routinely applied according to the current protocols for pediatric 
ALL and HD. It appears conceivable, that by such investigations, minor organ alterations could 
be missed and additional approaches comprising more sensitive structural or functional 
imaging would be essential to facilitate early recognition and possible timely management of 
developing still subclinical alterations. 
We here hypothesize that morphologic and free-breathing phase-resolved functional low-field 
(PREFUL) MRI may identify persistent pulmonary toxicity after treatment for childhood ALL 
and HD, respectively. Therefore, we propose to perform a cross-sectional, prospective, single-
center clinical pilot study using low-field MRI in children and adolescents during the first five 
years after the end of therapy. The results of this trial could contribute to the implementation 
of further investigation techniques in future standardized and structured LTFU care. 
 
 
References 
  
1. 
Erdmann F, Frederiksen LE, Bonaventure A, Mader L, Hasle H, Robison LL, et al. 
Childhood cancer: Survival, treatment modalities, late effects and improvements over time. 
Cancer Epidemiol. 2021;71(Pt B):101733. Epub 2020/05/29. doi: 
10.1016/j.canep.2020.101733. PubMed PMID: 32461035. 
2. 
Silverman LB. Balancing cure and long-term risks in acute lymphoblastic leukemia. 
Hematology Am Soc Hematol Educ Program. 2014;2014(1):190-7. Epub 2015/02/20. doi: 
10.1182/asheducation-2014.1.190. PubMed PMID: 25696854. 
3. 
Gebauer J, Baust K, Bardi E, Grabow D, Stein A, van der Pal HJ, et al. Guidelines for 
Long-Term Follow-Up after Childhood Cancer: Practical Implications for the Daily Work. 
Oncol Res Treat. 2020;43(3):61-9. Epub 2020/01/14. doi: 10.1159/000504200. PubMed 
PMID: 31931503. 
 

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6. Study aims 
Determination of the frequency of morphologic and functional lung parenchymal changes 
using low-field magnetic resonance imaging 
 
 
Hypotheses: 
- Lung parenchymal changes can be detected in pediatric and adolescent patients after 
completion of chemotherapy or chemotherapy and additional radiotherapy 
- Patients with changes do not present with clinical symptoms  
 
Primary Objective: 
- To determine the frequency of morphologic lung parenchymal changes using LF-MRI. 
 
Secondary Objectives: 
- To determine the frequency of functional lung parenchymal changes using LF-MRI. 
- Determination of the anamnestic frequency of clinical respiratory symptoms 
- To assess myocardial function by echocardiographic strain and strain-rate imaging 
 
 
Study type 
Prospective, monocentric, diagnostic study 
 

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7. Target variables 
Primary target variables: 
LF-MRT 
Changes of lung parenchyma 
 
Secondary target variables: 
LF-MRT 
Functional lung parameters (Ventilation 
match/mismatch, Perfusion 
match/mismatch, combined defects)  
Cardiopulmonary testing 
Oxygen uptake (VO2) 
peak oxygen uptake (VO2max) 
Respiratory exchange ratio (RER) 
Ventilatory anaerobic threshold (VT2) 
Carbon dioxide output (VCO2) 
Heart rate (HR) 
Heart Rate Reserve (HRR) 
Breath rate at VAT 
Breath rate reserve (BRR) 
minute ventilation (VE) 
O2 Pulse 
Heart rate variability (HRV) 
Exercise capacity (Borg Scale) 
Capillary blood gases and lactate 
Myocardial function 
At time 0 and after 6 months 
Blood sample 
Blood count*, Enterocytes*, Liver enzymes*, 
Retentionparamters* 
Pulmonary tests 
Lung function (VC%, FEV1%) 
Clinical parameters 
Age* 
Gender* 
Weight* 
Ethnicity* 
Time from therapy initiation/Interval until LF-
MRI 
Current medication* 
Secondary diagnoses* 
Clinical examination* 

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*Standard procedures/parameters routinely available in follow-up care 
 

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8. Study design 
 
Monocentric / multicentric 
This is a monocentric study 
 
Study arms: intervention/control 
Patients (early and late effects) fulfilling the inclusion criteria will receive an MRI of 
the lungs and lung function testing 
 
Randomization 
Randomization is not planned 
 
Blinding 
Blinding to the study is not possible. Blinding of patients/subjects is not necessary 
 
 

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Graphical design of study flow (Patient numbers for early and late therapeutic effects are 
referring to each of the two patient groups with ALL and HD.) 
 
 

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9. Study population 
In- and exclusion criteria 
 
Early therapeutic effects 
Late therapeutic effects 
Effects of hematopoietic 
stem cell transplantation 
Planned number of patients 
N=10 ALL 
N=10 HD 
N=10 ALL 
N=10 HD 
N=10 
Inclusion criteria 
- 
Diagnosed acute 
lymphatic leukemia 
or Hodgkin`s disease 
(HD) 
- 
Completed induction 
therapy or 
radiotherapy 
- 
From 5 years to <18 
years 
- 
Diagnosed acute 
lymphatic leukemia 
or Hodgkin`s disease 
(HD) 
- 
Completed intensive 
therapy or 
radiotherapy 
- 
From 5 years to <18 
years 
- 
Diagnosed acute 
lymphatic leukemia 
- 
Completed 
hematopoietic ste 
cell transplantation 
- 
From 5 years to <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/malforma
tions 
- 
Previous 
lung 
surgery 
- 
Injuries that do not 
allow physical stress 
diagnostics 
- 
Pregnancy, Lactation 
- 
Known 
pleural 
or 
pericardial effusion 
- 
Critical 
condition 
(requiring respiratory 
support, 
ventilation, 
oxygen, 
shock, 
symptomatic 
heart 
failure) 
- 
Marked 
thoracic 
deformities/malforma
tions 
- 
Previous 
lung 
surgery 
- 
Injuries that do not 
allow physical stress 
diagnostics 
- 
Pregnancy, Lactation 
- 
Known 
pleural 
or 
pericardial effusion 
- 
Critical 
condition 
(requiring respiratory 
support, 
ventilation, 
oxygen, 
shock, 
symptomatic 
heart 
failure) 
- 
Marked 
thoracic 
deformities/malforma
tions 
- 
Previous 
lung 
surgery 
- 
Injuries that do not 
allow physical stress 
diagnostics 

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- 
Rejection 
of 
MRI 
imaging 
- 
General 
contraindications for 
MRI examinations 
(e.g. electrical 
implants such as 
cardiac pacemakers 
or perfusion pumps, 
etc.) 
- 
Rejection 
of 
MRI 
imaging 
- 
General 
contraindications for 
MRI examinations 
(e.g. electrical 
implants such as 
cardiac pacemakers 
or perfusion pumps, 
etc.) 
- 
Rejection 
of 
MRI 
imaging 
- 
General 
contraindications for 
MRI examinations 
(e.g. electrical 
implants such as 
cardiac pacemakers 
or perfusion pumps, 
etc.) 
 
Recruitment channels and measures 
Patients (and parents) will be informed about the possibility to participate in the study in public 
notices and announcements on the homepage of the hospital as well as when visiting the 
pediatric clinic for hematology and oncology (including its outpatient clinics). If patients and 
their parents are interested to participate, they will be fully informed about the aims and 
methods (especially about the scientific/explorative nature of the study), the benefits and risks, 
and the revocability of participation in the study before giving their consent prior to study 
initiation. Patients in childhood and adolescence are additionally informed and educated about 
the study and its procedure in an age-appropriate manner. 
 
 
 

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10. Study procedures 
 
Procedures for informing and obtaining Consent 
Patients or subjects can only be enrolled in the study after written informed consent has been 
obtained. The written informed consent requires an oral and written explanation to the 
patients/subjects, as well as their parents or legal guardians, about the aims and methods (incl. 
scientific-explorative character of the study), benefits and risks as well as the revocability of 
the study participation. Children and adolescents are informed by means of age-appropriate, 
comprehensible patient information sheets. By giving written informed consent, the 
patients/participants as well as their parents/guardians declare that they agree with the 
collection and storage of study-relevant data and their review by monitoring or authorities. It 
must be clearly conveyed to the study participant that withdrawal of consent is possible at any 
time and without any disadvantage. Furthermore, all study participants/subjects and 
parents/guardians are informed that this study is a purely scientific study without any current 
diagnostic or therapeutic benefit. In case of incidental findings, the study participants/test 
persons and parents/guardians will be informed and further clarification will be initiated if 
indicated.  
The original consent form will be kept in the study folder at the study site. The patient/proband 
and parent/guardian will be given a copy of the patient information and consent form. The 
patient information and informed consent form can be found in the appendix of this study 
protocol. 
Study procedures 
After informing the patient/proband and parents/guardians, clinical data are collected. This 
includes the latest laboratory analyses, which are routinely performed in these patients. 
After appropriate education of parents/guardians/patient, the patients will be included. First, 
they undergo lung function testing (Duration approx. 10 minutes). Next, a native MRI 
examination (MRI examination without contrast medium administration) is performed. The 
duration is about 20 minutes. This is performed exclusively without sedation. Patients can 
remain in a lying position during the examination. During the examination, patients are 
protected by hearing protection from the noise generated. To enable the patient to make 
himself/herself heard, he/she is given a bell button shortly before the examination begins; 

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during the examination planning, communication is possible 
by means of an intercom system. In addition, the presence of 
a parent in the scanner room is possible during the entire 
examination time. 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 and the 
images produced are not evaluated diagnostically. 
During spiroergometry, the participants are subjected to a step 
test using treadmill spiroergometry. Spiroergometry is a non-
invasive test method. However, for a better assessment of the 
pulmonary capacity, a blood gas analysis at rest, at the 
anaerobic threshold (VAT) and during exertion is a useful 
additional parameter, so that we are planning a capillary blood 
sample at these three points in time. A lancet prick in the 
fingertip is necessary for this. The subject then has to put on 
a mask during the examination, has ECG electrodes attached 
to the thorax and has to run for a period of around 10 minutes 
at increasing speed up to the limit. Time schedule and study 
duration for the individual subjects: approx. 60 minutes per 
spiroergometry. 
Cardiopulmonary testing will also include echocardiographic strain and strain-rate imaging. 
This is a non-invasive method for the assessment of myocardial function defined as shortening 
or lengthening of the myocardium. This examination will take around 15 minutes. The patients 
lie quietly on an examination table without further measures being carried out or required. 
 
Acquisition of target variables 
- MRI imaging 
- Determination of demographic data 
 
Time schedule and duration of the study for the individual subjects/patients 
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.  
 
Total duration of the study 

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According to the number, the expected total duration of the study until inclusion of the last 
patient is approximately 18 months. 
11. Benefit-risk assessment 
 
All study-related risks 
 
Magnetic resonance imaging 
Unlike computed tomography, MRI does not use ionizing radiation, so no permanent side 
effects are expected. More than 1 million MRI examinations at higher field strengths (1.5/3T) 
are performed annually in Germany. Provided that the general contraindications for MRI 
examinations are observed, no serious side effects occur. MRI is therefore one of the safest 
examination procedures.  
The risks associated with an MRI examination emanate from the three main components of 
the MRI system. 
 
Static magnetic field 
The static magnetic field exerts forces and torques on ferromagnetic objects that can be so 
strong that the (mostly ferromagnetic) objects fly uncontrollably toward the magnet and can hit 
patients and staff (missile effect). The magnetic forces are proportional to the field strength B 
and the field change with location (dB/dz). These risks are lower with the low-field MRI system. 
Risks are further minimized by providing safety training to operators and excluding patients 
with ferromagnetic implants from the study. 
 
 
The gradient system 
Gradient switching can cause the appearance of magnetic phosphenes and nerve and muscle 
cell stimulation. Fast switched gradients produce high magnetic field changes per time (dB/dt), 
which induce voltages in the body. If a current flows through the tissue via nerve endings, for 
example, this can result in so-called peripheral nerve stimulation. However, the manufacturer 
of the gradient system guarantees compliance with the limits for gradient switching times and 
amplitudes recommended in the IEC 60601-2-33 guidelines.  Thus, nerve stimulation effects 
need not be considered further in the risk assessment of this study. 
Another safety-relevant effect of gradient fields is noise caused by gradient circuits due to 
current- and field-strength-dependent Lorentz forces in the gradient tube. These often 
unpleasant loud knocking noises occur especially during fast imaging processes where high 
currents flow through the gradients. Noise levels can rise up to 115dB for 1.5T tomographs 
(background noise: approx. 78dB). Due to the lower magnetic forces at 0.5T, we expect lower 

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noise levels. In addition, patients always wear hearing protection during the examination, so 
that the noise exposure remains well below the legal limit of 99 dB. 
 
The high-frequency system 
During the MR measurement, radiofrequency (RF) fields are sent into the human body, which 
are partially absorbed by the tissue and can lead to an increase in body temperature. The 
thermoregulatory response of human tissue to RF pulses has now been studied for 50 years. 
For example, using conservation of energy, it has been calculated that the body temperature 
of lightly clothed patients with undisturbed thermoregulation at room temperature increases by 
up to 0.6 °C when exposed to RF at 4 W/kg (63 MHz, 1.5 Tesla). The assumed specific 
absorption rate (SAR) of 4 W/kg body tissue corresponds to the so-called "controlled mode 
first level" (IEC safety guideline), which is also used as an upper limit in routine clinical imaging. 
The magnitude of the actual temperature rise is generally smaller because skin cooling was 
not considered in the calculations (worst case scenario).  
The body's energy production at rest is about 1.2 W/kg - equivalent to the energy conserved 
when wearing a thin sweater. Most healthy people are capable of compensating for 15 times 
this resting energy, and only a minimal increase in core body temperature occurs. Studies at 
1.5 T have shown that RF absorption in humans leads only to the expected cardiac adaptation 
and does not cause adverse health effects. Theoretically, a 63 kg person is even capable of 
emitting 1296 W to the environment through the skin by cardiac adaptation (i.e., maximum 
increase in blood flow) - this would correspond to a SAR of 20.6 W/kg. 
The same limits are observed with the 0.55 Tesla MRI system. At 0.55 Tesla, the wavelength 
of the radio waves used is significantly longer, so that the spatial distribution of the energy 
emission is more homogeneous and thus the risks tend to be lower. 
The spiroergometry 
If the infection is unknown, cardiopulmonary exertion can lead to inflammation of the heart 
muscles. A precise anamnesis regarding the constellation of infection as well as a clear 
explanation of the risks is therefore essential before exposure. A doctor is present at every 
examination. In addition, a risk of falling during treadmill ergometry cannot be ruled out with 
absolute certainty. To safely avoid injuries, the participants are secured with a safety rope. 
 
Capillary blood sampling 
The procedure of capillary blood sampling may cause additional discomfort or minor pain. 
Very rarely, problems with bleeding and infection can occur. 
 

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Echocardiographic strain and strain-rate imaging 
This ultrasound-based non-invasive measurement will take about 15 additional minutes, 
during which the patient lies on an examination table. Further procedures are not required 
through this method. There is no additional risk is associated with this method. 
 
 
Benefits associated with the study 
The data obtained in the studies may provide essential insights into the long-term effects 
chemotherapeutics in children. Therefore, the study may influence future clinical management 
and therapeutic regimes. 
 
Discontinuation Criteria 
Discontinuation criteria for the individual participant: 
Particularly in light of the inclusion of pediatric and adolescent participants, study participation 
will be discontinued if MRI cannot be performed without sedation.  
Study discontinuation for the individual participant will occur if: 
- an event occurs that may lead to endangerment of the patient or the staff, 
- the patient withdraws consent to participate in the study, or withdraws, 
- the patient does not comply with the instructions of the investigators and the operating 
personnel, 
The patient can stop the examination at any time without giving any reason. For this purpose, 
a so-called bell button is available to the patient during the MRI examination, the activation of 
which gives a signal with which the patient can draw the attention of the physician/examiner to 
him/herself, even while the measurement is in progress. Furthermore, the patient is in contact 
with the examiner via microphone and headphones between the individual measurements and 
can thus also verbally request the termination of an examination. In addition, the presence of 
a parent in the scanner room is possible during the entire examination time. Study participants 
may also discontinue the study at any time before, during, and after all other study-related 
examinations without providing a reason. 
 
Dropout criteria for the entire study: 
There is no provision for discontinuation of the entire study. 
 
Termination criteria for spiroergometry: 
Here we follow the termination criteria of the German Spiroergometric Society or DGSP 
(German Society for Sports Medicine and Prevention): 
• Reaching the maximum heart rate (200/min) 

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• No reserve of breathing available 
• RER > 1.15 
• Breath Equivalent > 35 
• VO2 plateau despite increasing exertion (O2 rise < 150 ml/min. over 30 sec.) 
• After exertion, idling for 2 minutes. 
• Abnormalities in blood pressure (> 2.5 hrs above 50th percentile, sudden drop or rise) 
• In treadmill ergometry with ECG: ST depression, ventricular extrasystoles 
 
Statement on medical justifiability 
The examinations will be performed exclusively on an approved MRI device using approved 
techniques. As the only significant difference to routinely applied MRI diagnostics, part of the 
data analysis will be performed with a novel software which is not yet applied in clinical practice 
and has not yet received the Conformité Européenne (CE) marking. The field strength used is 
significantly lower than the 1.5T and 3T scanners routinely used to date.  The risks are low as 
described above, especially since no measures such as contrast agent application are 
foreseen. Spiroergometry is an accepted and recognized method for examining the 
cardiopulmonary capacity of athletes and patients. It is also used extensively in patients with 
severe heart and lung disease. It is now an integral part of preoperative diagnostics to assess 
the surgical capability of older patients. It represents a harmless and non-invasive method for 
estimating the cardiopulmonary capacity of patients and is therefore also easy to carry out for 
children. 
The overall findings may help to estimate and minimalize the therapeutic risks for these 
patients. 
 
The study aims at age- and disease-specific findings that cannot be derived from data from 
adults. The personal benefit of the study for each participant is to receive information about 
their individual physical (cardiopulmonary) resilience and potential secondary harm to 
chemotherapeutic treatments. There is no need to recruit a completely healthy comparison 
group. 
 
 

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12. Biometry 
Explorative, hypothesis-generating study 
 
Power calculation 
No power calculation was performed as part of a pilot study. So far, there are no reliable 
preliminary data/measurements or similar to have conclusions about the frequency of possible 
changes. Therefore, in the context of this pilot study, a N=10 per group (patients with ALL, 
patients with HD, and patients after allogeneic hematopoietic stem cell transplantation) is 
considered reasonable. 
 
Statistical Methodology 
Continuous variables will be reported as mean with standard deviation, categorical variables 
as numbers with percentages if necessary. The occurrence of MRI changes is reported as a 
percentage of the population. All analyses are performed using GraphPad Prism (version 7.00 
or later, GraphPad Software, La Jolla, CA, USA), RStudio (version 1.1.456 or later, RStudio 
Inc., Boston, MA, USA), or IBM SPSS Statistics (version 24 or later, IBM Corp., Armonk, NY, 
USA). 
 

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13. Data management and data protection 
 
Data acquisition, storage 
All raw data, such as patient records, represent source documents. Their availability is ensured 
for routine monitoring. Participation of individual patients or subjects in the study is 
documented, and the study director maintains an independent list to identify participating 
patients. This list included name and date of birth as well as study date and pseudonymization 
abbreviation of the patients and subjects. The study director is responsible for the quality of 
data collection and storage. Data storage (total data) is performed on computers or specially 
designated network drives at Erlangen University Hospital. Comparable to routine, imaging 
data are transferred to the protected PACS (Picture Archiving and Communication System).  
 
Pseudonymization 
Prior to any scientific analysis of the materials and data of this study, all information will be 
pseudonymized according to the guidelines of the German Data Protection Act. 
 
Data transfer 
The data will not be passed on to third parties.  
The study results may be published anonymously, and it will not be possible to infer the identity 
of the participating individuals. The data will be kept for 10 years and then destroyed.  
 
Revocation, data deletion 
In case of revocation of the declaration of consent, data collected up to this point can be taken 
into account. The patient has the right to demand their destruction, provided that legal 
regulations do not prevent the destruction. 
 

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Contents are confidential. No disclosure to third parties. 
14. Handling of biomaterial 
Capillary blood samples will be used for measurement of blood count, liver enzymes, and 
retentionparamters as standard values routinely determined supplementary to pulmonary tests 
available in follow-up care. These samples will not be used in a different context nor will they 
be stored. No additional biomaterials are obtained. 
15. Insurance for partcipants 
No insurance is taken out due to the low study risk.  
16. Signature 
 
 
 
 
Dr. med. A. Karow 
Studienleiter Onkologie 
 
 
 
 
 
PD Dr. med. Ferdinand Knieling 
Studienleiter 
PD Dr. med. Rafael Heiß 
Studienleiter