Exercise Training in Patients With Myeloproliferative Neoplasms

During an incremental exercise test on a bicycle ergometer power output and gas exchange will be measured continuously. Afterwards the RCP (also known as second ventilatory threshold) will be assessed based on the inflection point of the slopes of the tidal volume (VE) and the carbon dioxide output (VCO2).

Evaluation of the MPN-10, a validated, patient-reported outcome questionnaire specifically designed to assess the symptoms and quality of life in patients with myeloproliferative neoplasms. MPN-10 assesses 10 key symptoms commonly experienced by MPN patients.

Scoring: 0-4 scale per item, total score ranges from 0 to 40. If the total score is reduced by 30% the binary outcome (yes/no) is fulfilled.

During an incremental bicycle exercise test until voluntary exhaustion gas exchange will be measured continuously breath by breath. Within the last stage, the highest oxygen uptake values from single breaths during 30 consecutive seconds are determined as the peak oxygen uptake.

To estimate the total and exercise-related physical activity, metabolic equivalents of task (MET) as MET-hours per week will be calculated, using the International Physical Activity Questionnaire (IPAQ-long) as self-reported outcome

The European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 is an internationally used, standardized questionnaire from the European Organization for Research and Treatment of Cancer (EORTC) that assesses health-related quality of life (HrQoL) in cancer patients, measuring functioning (physical, role, emotional, cognitive, social) and symptoms (fatigue, pain, nausea/vomiting). It uses scales from 0-100, where higher scores mean better function/HrQoL (for function scales) or worse symptoms (for symptom scales). Further, a summary score can be calculated by averaging 13 scales (after reversing symptom scales) to provide one overall measure of HrQoL, with higher scores meaning better functioning/HrQoL, and scores range from 0-100.

The Functional Assessment of Cancer Therapy - Leukemia (FACT-Leu) is a valid measure of leukemia-specific health-related quality of life (HrQoL) for acute and chronic disease. Assessed subscales include Physical Well-Being, Social/Family Well-Being, Emotional Well-Being, Functional Well-Being, and a Leukemia Subscale with overall 44 items that has to be responded on a 5 point Likert-type scale. Subscale scores and a total score with a range from 0 to 176 points are possible, with higher scores indicate better HrQoL.

During the incremental exercise test on a bicycle ergometer power output and gas exchange will be measured continuously. Afterwards the VT will be assessed based on the inflection point of the slopes of the carbon dioxide output (VCO2) and the ventilated oxygen (VO2).

Number of steps will be recorded by a wearable activity tracker (Vivoactive 5, Garmin, Olathe, Kansas, USA) during 7 consecutive days. Valid days will be averaged to get the outcome steps/day.

LDH is released into the bloodstream upon cellular damage or increased turnover. In patients with MPNs, elevated LDH levels are commonly observed and are associated with increased disease burden, tumor cell proliferation, and adverse prognosis. LDH serves as a non-specific but clinically useful biomarker of disease activity and metabolic stress.

Platelet count is a key component of the complete blood count and reflects bone marrow activity and hemostatic function. In MPNs abnormal platelet production is a hallmark feature, often leading to sustained thrombocytosis (elevated platelet count). Elevated platelet counts are associated with increased risk of thrombotic and hemorrhagic complications, which are major clinical concerns in MPN management.

GDF15 is produced by a variety of tissues in response to cellular stress, inflammation, oxidative damage, and mitochondrial dysfunction. Elevated serum GDF15 levels are associated with aging, chronic inflammation, and several hematologic and malignant conditions. In MPNs, GDF15 is often upregulated due to increased bone marrow stress, dysregulated hematopoiesis, and systemic inflammation. Higher GDF15 levels correlate with disease burden, symptom burden, and adverse outcomes, making it a potential biomarker of disease activity and systemic stress.

SIL-2R serves as a biomarker of immune system activation and lymphocyte proliferation. Elevated serum levels of sIL-2R are associated with chronic inflammation, autoimmune disorders, and hematologic malignancies. In MPNs, persistent immune dysregulation and chronic inflammation contribute to disease pathogenesis and symptom burden, and sIL-2R levels often correlate with disease activity, inflammatory burden, and clinical progression.