The use of high-dose chemotherapy (HDC) combined with autologous stem cell transplantation (ASCT) has improved the outcome of haematological malignancies such as multiple myeloma (MM) and (non-)Hodgkin's lymphoma (NHL/HL). It has become standard of care in these diseases in first line and relapse, respectively. However, this treatment has long term negative side effects. Symptoms like fatigue [1–7] and dyspnoea [1, 4, 5, 8] are highly prevalent among ASCT survivors. In addition, survivors have a reduced global quality of life, role and physical function when compared to population norms . For instance, up to 60% of the patients 3 years post-transplant had a compromised ability to engage in activities as carrying a heavy bag and taking a long walk . 23-56% of the patients were not able to return to work during the course of the first year after ASCT [6, 11–13].
The persistent fatigue and deficits in health related quality of life (HRQoL) might reflect a self-perpetuating condition [14–18]. Cancer, its treatment and the associated bed rest can lead to poor physical fitness (a.o. impaired cardiorespiratory function and reduced muscle strength). As a result, greater effort is required to fulfil the activities of daily living, and performance of these activities can induce an abnormally high level of fatigue. In order to minimize fatigue, patients will limit physical activities, which will eventually lead to a greater decline in physical fitness. An exercise intervention might break this downward sequence [14–18]. Previous studies have shown that exercise intervention programs can improve physical fitness, fatigue level and quality of life among haematological cancer patients [14, 15, 17, 19–25]. However, based on systematic reviews, Liu et al. (2009) and Wiskemann & Huber (2008) conclude that more high quality research is necessary [26, 27]. In the review of Liu et al. (2009)  only three of the ten included studies were randomized controlled trials. The overall quality of many studies reviewed was limited, with shortcomings related to trial design, sample size, choice of comparison groups, outcome measures and duration of follow up . Wiskemann & Huber (2008) reached similar conclusions . Both reviews show that there is a need for well designed, randomized controlled trials that verify the findings of the previous trials and can lead to evidence-based interventions.
In addition to the limited methodological quality, the trials performed to date were heterogeneous in terms of the type of exercise interventions studied. Most of the studies focussed on isolated aerobic exercise during or after the stem cell transplantation. Resistance exercise programs and combined training strategies have been evaluated more rarely . This is somewhat surprising since muscle atrophy is a common problem in cancer patients [28–30]. The muscle athrophy is likely to be even more pronounced in patients undergoing HDC and ASCT because of the nature of drugs being used (a.o. high dose glucocorticoids) , and because of the morbidity associated with the neutropenic phase after ASCT, which often leads to prolonged bed rest. As considerable evidence suggests that the ability to perform physical tasks in daily life is determined by a certain threshold level of muscular strength , it seems important that exercise interventions not only aim to improve aerobic capacity but also aim to minimize muscle atrophy or even stimulate muscle hypertrophy.
To our knowledge, there are currently no data on the cost-effectiveness of exercise intervention programs in cancer patients. The common inability to return to work during the course of the first year after ASCT [6, 11–13], the frequent use of health care resources [32, 33] and the reported financial problems by patients [8, 34] show the importance of determining the cost-effectiveness of exercise intervention programs.
The current study will evaluate an individualized high intensity strength and interval training program developed and pilot-tested by De Backer et al. (2007, 2008) at the Maxima Medical Center (MMC) in Veldhoven, the Netherlands [35, 36]. This program has shown promising results with respect to rehabilitation of cancer patients after chemotherapy, but needs to be further explored and tested in ASCT survivors.
The aims of the current study are (1) to determine the effectiveness of a state-of-the-art individualized high intensity strength and interval training program with respect to physiological and psychological status in patients with MM, NHL or HL who have recently undergone HDC followed by ASCT; and (2) to evaluate the cost-effectiveness of this exercise program.
We hypothesize that this exercise program will lead to (1) improved physical fitness; (2) lower levels of fatigue; (3) less mood disturbance; (4) higher levels of daily activities; (5) improved HRQoL; (6) a higher partial and full return to work rate; and that the program (7) will be cost-effective when compared to standard care only.