Symptoms, functional status, and altered immunity in survivors of allogeneic hematopoietic stem cell transplantation with chronic graft-versus-host disease (cGVHD)

Chronic graft-versus-host disease (cGVHD) is a prevalent late effect of allogeneic hematopoietic stem cell transplant (HSCT), and is associated with significant morbidity and mortality. No previous research has examined symptoms and functional status in a sample comprised exclusively of HSCT survivors with cGVHD, and little is known about the relationship between cGVHD symptoms and the immunologic milieu. Knowledge of these aspects would inform the development of nursing interventions to ameliorate symptoms and improve functional status, thereby enhancing quality of life. This cross-sectional study of 100 long-term (median of 31 months posttransplant) allogeneic HSCT survivors with cGVHD characterized symptoms, functional performance, and functional capacity, identified subgroups with differing cGVHD symptom profiles, and explored whether those symptom profiles were associated with patterns of plasma cytokine expression. The mean symptom bother score was 28.3 (on a 0-100 scale), reflecting moderate symptom bother. The median number of symptoms was 16, with a median of 5 of those symptoms identified as moderately to extremely bothersome. Using latent profile analysis, three symptom subgroups were identified: a group that was low on all symptoms (n=54), a group with prominent oral and gastrointestinal symptoms (n=15), and a third group with prominent eye, muscle/joint, fatigue, and mood symptoms (n=31). Survivors in the two subgroups with prominent symptoms had a level of functional performance that was significantly inferior to that of the low on all symptoms' subgroup. Intensive immunosuppression, reduced functional capacity and prominent symptom bother were significant independent determinants of impaired functional performance (p<.001), together accounting for 56% of the variation in functional performance. Symptoms had both a direct and an indirect negative effect on functional performance, with the indirect effect of symptoms on performance mediated by functional capacity (Sobel test p=.004). Multinomial logistic regression, controlling for age, cGVHD severity, intensity of immunosuppression, and posttransplant lymphocyte reconstitution revealed four cytokines (soluble BAFF, IL-6, soluble TNF-RII, and MCP-1) that significantly (p<.05) distinguished the symptom subgroups. Results suggest an opportunity to improve functional performance by reducing cGVHD symptoms and improving functional capacity. Testing of mechanism-targeted nursing interventions and further study of the association between cGVHD symptoms and candidate biomarkers are warranted.