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Abstract

Physical performance is not only a fundamental requirement for the activities of daily life, for family and work, but also for demanding phases of our lives, such as illness. There are substantial recommendations and statements for physical exercise to strengthen the physical performance in healthy individuals, for chronic diseases, but also specifically for various oncological diseases. For hemato-oncological patients, the disease itself, as well as the intensive treatment, represents a great challenge for physical resources. Even though methods of allogeneic hematopoietic stem cell transplantation (allo-HCT) have improved remarkably in recent years, intensive therapy requires patients to be in sufficient physical condition. Various tools have been developed for the assessment and risk stratification of patients in order to estimate the chances of the treatment. Various risk profiles can be illustrated, such as the presence of previous diseases or general comorbidities. However, in the past, modifiable risk factors such as low physical fitness (e.g. cardiorespiratory fitness) for higher symptom burden or worse outcome have also been identified. Against this background, physical exercise is becoming increasingly relevant and some exercise interventions during different phases of the disease are demonstrating promising health-effects. The evidence regarding the patient’s healthstatus including physical performance and a successful implementation of exercise interventions prior to allo-HCT is still understudied. The question arises whether modifiable factors exist, that can be identified and subsequently changed in order to improve physical performance and therefore the outcome of the hematological cancer-treatment. As before, further substantiated descriptions of this patient sample are necessary and too little is known about possibly modifiable and influencing factors prior allo-HCT. Therefore, the aim of this dissertation is to contribute to closing this research gap. It investigates whether the main parameters of physical performance the cardiorespiratory fitness (CRF) and muscle strength are affected prior allo-HCT and their influencing variables. As a logical continuation of this question, the possibility of an exercise intervention shortly prior to allo-HCT in order to improve the physical performance in the short term is explored. The first manuscript investigated CRF in allo-HCT candidates (n=194) and compared these data to healthy controls. Our results demonstrated a significantly decreased CRF in allo-HCT candidates prior transplantation. We found that higher Body Mass Index (BMI) values, low physical activity, amount of cardiotoxic agents and low hemoglobin-level before allo-HCT negatively impact CRF prior allo-HCT. On this basis, describing risk factors for low CRF before allo-HCT could lead to a targeted approach to exercise intervention before rehabilitation that identifies patients with the greatest need. The second manuscript examined muscle strength in allo-HCT candidates (n=212). Again, this parameter was shown to be decreased in allo-HCT candidates immediately prior transplantation and high deviations from a healthy reference population are revealed. We showed that especially younger patients of male gender and possibly with lower hemoglobin values are affected by muscle weakness. Our regression analysis showed, that muscle strength is significantly influenced by female gender, lower BMI, higher age and higher Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) scores. In the context of increasingly older allo- HCT candidates, comorbidities (HCT-CI) should also be considered in the risk assessment. We assumed that future exercise interventions should focus on resistance training (RT) for the lower extremities, as they are more affected and play the main role in supporting and moving during weight-bearing tasks and daily activities. The third manuscript, in turn, provided a research contribution to the question of whether pretraining - adopted shortly before the start of allo-HCT - can be feasible and effective. Due to low recruitment numbers, the study had to be terminated. This shows the limitations of the implementation method, but the training-specific content is promising. Despite of a very short time period, we were able to show that a high intensity interval training (HIIT) and a high-to moderate intensity RE is feasible and is able to improve physical performance. The obtained promising data on n=14 patients demonstrated significant effects on CRF, 6MWT performance, hand grip strength and patient-related outcomes (PROs). Obtained MVIC values show a positive trend. For future studies, it seems important to move the timing of recruitment further forward, in order to reach and include a larger number of candidates. In summary, this dissertation adds to the body of research concerning hematological malignancies and the importance of a patients’ health status prior allo-HCT. It provides comprehensive information about physical performance on the basis of CRF and muscle strength. We could demonstrate that these are already reduced in allo-HCT candidates shortly before the start of transplantation. The investigation of influencing factors of CRF and muscle strength contributes to a more precise identification of possible high-risk subgroups. This, along with the fact that exercise training just before allo-HCT seems to be feasible and effective, provides decisive information for future research, for the implementation of exercise programs and for individualized treatment strategies.