Physical Exercise Is Possible in Patients with Critical Cytopenia Undergoing High- Dose Chemotherapy for Acute Leukaemia or Aggressive Lymphoma

Objective: Patients undergoing high-dose chemotherapy for Acute Leukaemia or Aggressive Lymphoma are not only suffering from the direct side-effects of chemotherapy such as infections due to long-lasting immuno-suppression and aplasia, but also from marked fatigue and the inability of normal physical activity. Furthermore, especially in patients with severe thrombocytopenia, anaemia and leukopenia, doctors recommend to abstain from physical exercise due to the risk of potential bleeding and tissue damage. The normally recommended cut-off level to perform exercise is 50.000 platelets per microliter or haemoglobin of 8g/dl. This leads to a vicious cycle of loosing physical strength and muscles with subsequent development of treatment related kachexia and an increased treatment mortality. As a number of publications focus on the importance of physical exercise in patients with solid tumours, increasing evidence is found that suggests positive effects on major clinical endpoints such as rate of infection, quality of life and even relapse rate and overall survival. With this work, we intended to address whether that intense supervised ergometer training is feasible in patients with severe pancytopenia and whether it has any effect on patients undergoing high-dose chemotherapy. Furthermore, this study was initiated as the groundwork for a large phase III randomised trial.

Patients and Methods: A total of 12 patients with haematologic diseases (median age 44 years, range 25–66, 7 AML, 1 ALL, 4 hgNHL) were included in this pivotal trial. All patients started the exercise program parallel to high dose chemotherapy. Training consisted of at least three weekly ergometer trainings of 15–30 minutes; sub maximal intensity of training was defined by WHO criteria not allowing a higher heart rate of more than 180-age. Training was based on individual coaching and vital sign monitoring. Platelet or red blood cell transfusions were administered in a highly restrictive manner (platelets <10.000/μl or haemoglobin < 8g/dl).

Results: 8 out of 12 patients could be fully trained and evaluated during the complete hospitalisation phase, the remaining 4 patients were treated only partially due to medical or organizational reasons. The median time of treatment was 7.4weeks (+2.8, range 2–11 weeks). For those fully treated 8 patients, sub maximal relative endurance capacity (Watt/body weight) showed significant improvement (p=0.035) for the time of hospitalisation. Median platelet count over time was 27.000/μl with a medium minimal count of 8.000/μl; medium haemoglobin was 9.2g/dl. In terms of life quality, no significant change from admission to discharge from hospital could be found.

Conclusion: Although only 8 out of 12 patients could be fully examined in this small pivotal trial, significant improvement of sub maximal relative endurance capacity could be demonstrated during chemotherapy. Furthermore, no side effects even in severely thrombocytopenic or anaemic patients were documented. Therefore, a large randomised Phase III trial has just been opened to evaluate clinical and immunologic effects of physical exercise in these critically ill patients.