Monitoring Neurocognitive Dysfunction and the Impact of Metabolism and Physical Capacity After Paediatric HSCT

Waist circumference will be measured at the level of the superior border of the iliac crest, at the end of a normal expiration with a tape measure to the nearest 0.1 cm, as suggested by The US National Cholesterol Education Programme. Patients will be classified according to the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) criteria for Metabolic Syndrome as defined in the 2005 scientific statement (Grundy et al., 2005).

Blood samples will be drawn from a cannula placed in an antecubital vein or a dorsal vein in the hand. Patients will be classified according to the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) criteria for Metabolic Syndrome as defined in the 2005 scientific statement (Grundy et al., 2005).

Blood samples will be drawn from a cannula placed in an antecubital vein or a dorsal vein in the hand. Patients will be classified according to the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) criteria for Metabolic Syndrome as defined in the 2005 scientific statement (Grundy et al., 2005).

Blood samples will be drawn from a cannula placed in an antecubital vein or a dorsal vein in the hand. Patients will be classified according to the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) criteria for Metabolic Syndrome as defined in the 2005 scientific statement (Grundy et al., 2005).

Blood pressure will be measured on the upper arm while sitting in the suppine position, after 10 minutes of rest, with an automated blood pressure monitor. Blood pressure will be measured three times, or untill there is less than 10 mmHg difference between measurements. The final blood pressure will be a mean of the two last measurements. Patients will be classified according to the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) criteria for Metabolic Syndrome as defined in the 2005 scientific statement (Grundy et al., 2005).

Measurement of hip circumference at the widest part of the buttocks with a tape measure, to the nearest 0.1 cm.

Test of lower extremity isometric knee extension strength: will be assessed by measuring the rate of force development, maximal isometric force, and dynamic force capacity using a special-build strength ergometer (Gym 2000®) with a dynamometer (US2A100 kg, Holtinger, Germany) and amplifier. Data is collected through an AD-card (100 HZ) with customized software (LabVIEW ®, National Instruments, Texas, USA). The participant will be seated during the test. The participant's thigh, pelvis, and torso will be securely strapped to minimize movement and isolate the knee extension muscles. For the isometric test, the participant will be instructed to push against the lever arm of the dynamometer as hard and as quickly as possible for a few seconds without any movement at the knee joint.

Handgrip strength will be measured while standing, with the elbow free from the body and flexed 90 degrees. Participants will press as hard as possible on a handheld dynamometer. Handgrip strength (kg) is measured twice for both arms and the highest result will be used in the analyses. Handgrip strength is a measure of strength in the underarm and correlate with overall physical impairment.

Participants will sit on a chair with both feet flat on the ground. Subsequently, participants will be instructed to stand up, walk 3 meters, turn around, walk back, and sit down as fast as possible. Each participant will perform the test three consecutive times and the fastest test will be used for the analyses. The timed-up-and-go test depends on lower body muscular strength and balance and reflects a person's ability to move in an everyday setting.

Sit-to-Stand 30 sec: The participant sits on a chair allowing the participant to flex the legs at a 90 degree angle. The participant is instructed to stand up straight, and return to sitting, as many times as possible in 30 sec. The arms should be crossed in front of the body or hanging by the side. Number of repititions is the outcome.

Sit-to-Stand 60 sec: The participant sits on a chair allowing the participant to flex the legs at a 90 degree angle. The participant is instructed to stand up straight, and return to sitting, as many times as possible in 60 sec. The arms should be crossed in front of the body or hanging by the side. Number of repititions is the outcome.

performed on an electrical-break ergometer bicycle (Lode Corival Pediatric or Monark Ergomedic 839 E) using a modified Godfrey protocol. The participant will be instructed to keep a steady pace (70-80 rpm), while the workload increases gradually with 10-25 watts pr. minute until exhaustion. Oxygen uptake (VO2), heart rate (HR), minute ventilation (VE), respiratory exchange ratio (RER), breathing frequency (BF), and tidal volume (TV) will be measured continuously during the test using a transportable a portable Cortex Metamax 3B wireless spirometry system (Cortex, Leipzig, Germany). The participant will breathe into a Hans Rudolph Valve (2-wat NRBV, Hans Rudolph Inc., Kansas City, MO, USA). Heart rate and oxygen saturation will be measured during the test. Furthermore, two objective criteria need to be fulfilled before the test is valid: 1) heart rate >85% of estimated maximal heart rate 2) respiratory exchange ratio (RER)>1.1. The primary outcome will be the peak oxygen uptake (V02max

Maximal leg extension power: maximal voluntary muscle force will be measured from both legs following a fixed protocol. Leg extensor power will be measured using an extension Power Rig (Nottingham Power Rig, Queen's Medical Centre Nottingham, NG7 2UH, United Kingdom), with subjects positioned with joint angles as if the participant was rising from a chair. Participants are carefully instructed to keep their hands across the chest and to not move the upper body while pushing. Verbal encouragement will be given to ensure maximal performance. The participants extend one leg as forcefully as possible, and the velocity of the flywheel is measured by an opto-switch and used to calculate average leg extensor power in the push. Dominant leg will be tested, a minimum of 5 attempts is carried out for each leg, however the participant continues until two attempts are lower than the maximum. The result is expressed in watt (W).

The PedsQL 4.0 Generic Core Scales assess health-related quality of life in children across four domains: physical functioning, emotional functioning, social functioning, and school functioning. The instrument uses a 5-point Likert scale (0 = never a problem; 4 = almost always a problem) - lower score meaning better outcome.

The PedsQL Multidimensional Fatigue Scale assesses fatigue in children in three domains: general fatigue, sleep/rest fatigue, and cognitive fatigue. It uses the same 5-point Likert scale (0 = never a problem; 4 = almost always a problem) - lower score meaning better outcome.

The PROMIS® Cognitive Function Short Form 8a is an 8-item self-report questionnaire assessing perceived cognitive functioning in the past 7 days. It evaluates aspects such as memory, mental clarity, and concentration. Each item is scored on a 5-point Likert scale ranging from 1 ("very often") to 5 ("never") - higher scores indicate better subjective cognitive functioning.

The PROMIS® Physical Activity Short Form 4a is a 4-item self-report questionnaire that assesses the frequency and intensity of physical activity during the past 7 days. Items are rated on a 5-point Likert scale, with higher scores indicating higher levels of physical activity.

The Strengths and Difficulties Questionnaire (SDQ) is a brief screening tool used to assess emotional and behavioral functioning. It consists of 25 items covering five subscales: Emotional Symptoms, Conduct Problems, Hyperactivity/Inattention, Peer Relationship Problems, and Prosocial Behavior. Each item is rated on a 3-point scale: "Not true" (0), "Somewhat true" (1), or "Certainly true" (2). A Total Difficulties Score (0-40) is calculated by summing four of the five subscales (excluding Prosocial Behavior), where higher scores indicate more emotional or behavioral difficulties. Higher Prosocial scores (0-10) indicate better social functioning.

Age-appropriate versions of the SDQ will be used: parent- and self-report forms for children and adolescents, and self-report form for participants aged 18 years and older.

The Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2), is a standardized questionnaire assessing executive functions in everyday settings through parent or teacher reports. The questionnaire consist of 63 items (rated 1= never, 2 = sometimes, 3 = always). Higher scores indicate greater executive dysfunction.

The Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS) is a standardized questionnaire used to assess the severity of ADHD symptoms based on parent or teacher reports. Scores are calculated using standardized methods and normed according to Danish age- and gender-specific normative data. The scale consists of items rated on a 4-point scale (0 = never or rarely 3 = very often). Higher scores indicate greater severity of ADHD symptoms.