Individualized exercise program for the treatment of severe fatigue in patients after allogeneic hematopoietic stem-cell transplant: a pilot study.

Chronic cancer-related fatigue in otherwise asymptomatic post-allogeneic hematopoietic stem cell transplant (HSCT) patients is common and debilitating. This pilot study investigated whether patients with no clinical or psychological abnormalities but severe fatigue would respond to an individually adapted aerobic exercise program. Participants were 12 patients (eight male, and four female patients), median age 47 years and 41 months post-HSCT with a variety of hematopoietic cancer diagnoses. All underwent a 12-week individualized mild aerobic exercise program, preceded by a 4-week introduction and baseline testing phase. Psychological measures included fatigue, mood and depression. Exercise-related physiological outcomes included power output at ventilatory threshold 2 (VT2) and associated changes in stroke volume, heart rate, blood lactate concentration and ratings of perceived exertion. Patients were assessed for fatigue before, immediately after and at 3, 6, 9 and 12 months post-program. Significant improvements were found on both measures of fatigue (both P<0.001), with a very large effect size of 1.82 on the The Functional Assessment of Cancer Therapy - Fatigue Module, which were maintained over the follow-up period. Exercise testing revealed a mean increase (P<0.001) of 28% in power output at VT2 with an increase (P<0.001) in stroke volume and a decrease (P<0.001) in heart rate, blood lactate and perceived exertion at pre-intervention VT2 power output.

The human intracellular Mx-homologous protein is specifically induced by type I interferons.

The murine Mx-1 protein is one of the best biochemically and functionally characterized interferon (IFN)-induced proteins that is necessary, and sufficient, for providing resistance to murine cells against viral influenza infection. Recently an intracellular human protein homologous to the murine Mx-1 protein has been identified by means of a specific monoclonal antibody. The restricted induction of this intracellular protein in human mononuclear cells (MNC) by various cytokines was investigated. MNC from 26 of 28 healthy people and 35 of 36 cancer patients before IFN-alpha therapy had no detectable Mx-homologous protein. Incubation of human MNC with IFN-alpha and IFN-beta for 24 h at different concentrations led to a dose-dependent induction of the Mx-homologous protein. All IFN-alpha or IFN-beta preparations tested were equally effective in eliciting this intracellular protein. IFN-gamma induced only 1% of the Mx amount elicited by type-1 IFN compared on a weight basis. Neither interleukin (IL) 1 nor IL3, IL4, IL5, IL6, tumor necrosis factor-alpha/beta, granulocyte colony-stimulating factor (CSF) or granulocyte macrophage-CSF at any of the concentrations tested were capable of eliciting any detectable amount of the Mx homolog, while IL2 was a poor Mx-homologous protein inducer. In the presence of high-titered IFN-alpha antisera both IL2 and IFN-gamma were unable to stimulate this protein, proving that IFN-gamma and IL2 indirectly induce the Mx homolog via IFN-alpha. Therefore, the human Mx-homologous protein is a strictly by type I IFN-regulated protein in human peripheral blood lymphocytes.