Energy and substrate metabolism in patients with chronic extensive graft-versus-host disease

Background. Allogeneic stem cell transplantation is frequently complicated by graft-versus-host disease (GVHD), Weight loss is one of the characterist ic features of GVHD. The etiology of weight loss in GVHD is not completely understood. Methods. We measured resting energy expenditure (REE) and substrate oxidati on rates by indirect calorimetry in patients with stable chronic extensive GVHD under immunosuppressive therapy (n=13) and sex-, age-, height-, and we igh-matched healthy controls (n=13) in order to evaluate metabolic changes in these patients. Measurements were done on day 518+/-261 after allogeneic stem cell transplantation in the postabsorptive state. Serum concentration s of glucagon, norepinephrine, tumor necrosis factor-alpha, interleukin-6, and free fatty acids were determined. Results. Patients showed a maximum weight loss of 22% during their course o f GVHD; nevertheless, they regained 15% of total body weight (TBW) during s uccessful treatment of GVHD, Indirect calorimetry showed an increase in REE per kilogram of TBW (patients, 21.8+/-3.1 kcal/kg TBW/day; controls, 19.9/-2 kcal/kg TBW/day; P<0.05). Respiratory quotient (patients, 0.79+/-0.04, controls, 0.86+/-0.04; P<0.005) and non-protein respiratory quotient (0.78/-0.05 and 0.87+/-0.05, respectively; P<0.005) were decreased in patients, GVHD patients had elevated serum glucagon and norepinephrine concentrations , whereas tumor necrosis factor-<alpha> and interleukin-6 were in the norma l range. Conclusions. Patients with chronic extensive GVHD show an increase in REE a nd alterations in fat and carbohydrate oxidation rates. These changes seem to be the result of increased action of glucagon and norepinephrine.