• treatment-related symptoms;
  • inflammatory cytokines;
  • allogeneic HSCT;
  • MDASI;
  • nadir;
  • longitudinal study;
  • mixed-effects modeling



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.


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.


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.


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. Cancer 2008. © American Cancer Society.