Graft-versus-host disease and the effects of exercise.
Allogeneic hematopoietic stem cell transplant (allo-HSCT) is the only curative option for many patients with leukemia, primary or acquired marrow failure, primary immunodeficiency or inborn genetic diseases.
Advances in hematologic cancer care in the last 3 decades have led to an expanding population of long-term survivors, many of whom suffer severe side effects, particularly those related to graft-versushost disease (GVHD). GVHD is a potentially multi-systemic disorder caused by donor lymphocytes that destroy host tissues. Especially in its chronic form, cGVHD generates considerable morbidity and compromises the physical capacity of patients.
Exercise has therapeutic benefits on many systems in the body because working skeletal muscles produce numerous secreted factors (‘myokines’) with potential drug-like effects such as IL- 6 (an anti-inflammatory cytokine when released during exer- tion), secreted protein acidic and rich in cysteine (SPARC) or calprotectin (with potential anti-tumorigenic effects). This article describes the pathophysiological aspects of disease and exercise therapey, collected from animal and human studies.
Although exercise training as an adjunct therapy to improve health outcomes after allo-HSCT shows promise (improved physical fitness and QoL and possibly immune function while attenuating fatigue), there is a need for more randomized control trials that focus specifically on GVHD.
GVHD is a frequent complication of allo-HSCT and consists of the destruction of host tissues by donor effector lymphocytes. The incidence of the acute form of GVHD (aGVHD) has been estimated at 10%-80%, with symptoms usually developing 2-3 weeks post allo-HSCT, and 30-70% for chronic GVHD (cGVHD) with an onset of 4-6 months post transplantation.
Mortality rates of 15-40% have been reported for patients with aGVHD and 30-50% for those with cGVHD, which has a more aggressive, multi-systemic nature. In addition, GVHD causes severe morbidity, and allo-HSCT survivors with GVHD show impaired physical and social behavior, and undergo a worse physical and psychosocial recovery than survivors without this complication. Quality of life (QoL) is thus severely compromised. First line treatment is with steroids, which often fails and comes with a whole range of side effects. Clinicians are therefore turning to the multifold benefits and immunoregulatory of exercise as a possible means to improve clinical outcomes.
This paper reviews the main features of this life-threatening disease and discusses the rationale and preliminary findings supporting the effects of exercise training in GVHD.
The beneficial effects of moderate-intensity exercise on immune function, at least in non-immunocompromised individuals, have been well established. Up to date, several studies have been conducted in allo-HSCT patients, with positive effects despite the heterogenous nature of the studies.
Since GVHD is primarily an immunoreactive disorder, the authors call fo more RCTs with clear outcome measures such as hospitalization time, exercise tolerance, physical functioning and emotional and social well-being, while exploring potential immunomechanisms underpinning the beneficial effects of exercise.
Exercise as medicine; no longer a futuristic concept!
> From: Fiuza-Luces et al., Exerc Immunol Rev 21 (2015) 80-112. All rights reserved to International Society of Exercise and Immunology. Click here for the Pubmed summary.