Abstract
BACKGROUND: During the time of lowest white blood cell count (nadir) of allogeneic hematopoietic stem cell transplantation (allo-HSCT), cancer patients suffer from tremendous symptom burden related to therapy that requires intensive patient care. However, the mechanism underlying the development of multiple symptoms has not been established. METHODS: To explore the role of inflammatory cytokines in the development of treatment-related symptoms, we studied dynamic changes in symptoms and in serum concentrations of inflammatory cytokines (interleukin [IL]-6, IL-8, soluble tumor necrosis factor receptor 1 [sTNF-R1], IL-1 receptor antagonist, and IL-12p40p70) from pretherapy throughout the first 30 days of allo-HSCT in 30 patients with acute myelogenous leukemia or myelodysplastic syndrome. We measured multiple symptoms repeatedly using the M. D. Anderson Symptom Inventory. Mixed-effects modeling was used to analyze longitudinal data. RESULTS: In response to conditioning and stem-cell infusion, serum levels of IL-6 and the severity of multiple symptoms increased rapidly and peaked at nadir. From baseline to nadir (approximately Day 8 post-transplantation), increase in IL-6 was significantly associated with worsening of the most severe symptoms (fatigue, poor appetite, pain, drowsiness, dry mouth, and disturbed sleep; P< .01). During the first 30 days after transplantation, increases in IL-6 (P< .001) and sTNF-R1 (P< .05) significantly predicted the increasing severity of these symptoms. CONCLUSIONS: These results suggest that release of systemic inflammatory cytokines, mainly IL-6, corresponds to an increase in treatment-related multiple-symptom burden during the nadir period of allo-HSCT.