Immune Responses Contribute to Depression, Fatigue, and Pain in Hematopoietic Stem Cell Transplant Recipients

Depression, fatigue, and pain are prevalent and distressing quality of life concerns for individuals recovering from hematopoietic stem cell transplantation (HSCT). Recent research in other cancer populations suggests inflammatory cytokines can activate central nervous system pathways, evoking adverse behavioral responses including depressed mood, fatigue, and pain. We hypothesized that inflammatory responses also contribute to these symptoms among HSCT recipients. Participants (24 allogeneic and 68 autologous transplant recipients) completed well-validated measures of depressive symptoms, fatigue, and pain prior to transplant and 30, 100, and 200 days post-transplant. Circulating proinflammatory (IL-6, TNFα) and regulatory (IL-10) cytokines were measured by ELISA in peripheral blood plasma at the same time points. Subject-level fixed effects and mixed effects linear regression models were employed to examine relationships between cytokine levels and quality of life assessments. Results indicated that depression and fatigue were most severe 30 days post-transplant, with allogeneic recipients showing markedly slower improvement than autologous recipients at later assessments. Pain did not change significantly over time. Among individual patients, changes in IL-6 levels across the assessment points were associated with corresponding changes in depressive symptoms (t = 2.0, p = .048), fatigue (t = 2.7, p = .008), and pain (t = 2.0, p = .048), after adjusting for the effects of time since transplant. Similarly, participants with elevated IL-6 levels reported more severe depression (z = 2.9, p = .004), fatigue (z = 2.9, p = .004), and pain (z = 3.0 p = .003) compared to participants with low/normal IL-6 levels. All models adjusted for graft type and recipient's age. Similar relationships were seen for IL-10, while TNFα was not significantly associated with symptoms. Results provide evidence for a novel biobehavioral pathway by which inflammatory processes secondary to treatment and/or treatment-related complications may contribute to depression, fatigue, and pain among HSCT recipients. Findings may assist health care providers in identifying patients at risk for this constellation of symptoms.