title: Inflammatory markers and development of symptom burden in patients with multiple myeloma during autologous stem cell transplantation.
abstract: OBJECTIVE
  Increasing research suggests that inflammation mediates symptom development. In this longitudinal study, we examined inflammatory factors related to the development of high symptom burden during autologous hematopoietic stem cell transplant (AuSCT) for multiple myeloma.
  
  
  METHODS
  Patients (n = 63) repeatedly reported symptom severity on the MD Anderson Symptom Inventory multiple myeloma module (MDASI-MM) and contributed blood samples periodically for up to 100 days after AuSCT for inflammatory marker assays. The temporal associations between serum inflammatory marker concentrations and symptom severity outcomes were examined by nonlinear mixed-effect modeling.
  
  
  RESULTS
  Fatigue, pain, disturbed sleep, lack of appetite, and drowsiness were consistently the most severe MDASI-MM symptoms during the study. Peak symptom severity occurred on day 8 after AuSCT, during white blood cell count nadir. Patterns of serum interleukin (IL)-6 (peak on day 9) and soluble IL-6 receptor (sIL-6R; nadir on day 8) expression paralleled symptom development over time (both P < 0.0001). By univariate analysis, serum IL-6, sIL-6R, IL-10, C-reactive protein, macrophage inflammatory protein (MIP)-1α, sIL-1R2, sIL-1RA, and soluble tumor necrosis factor receptor 1 were significantly related to the most severe symptoms during the first 30 days after AuSCT (all P < 0.05). By multivariate analysis, IL-6 (estimate = 0.170; P = 0.004) and MIP-1α (estimate = -0.172; P = 0.006) were temporally associated with the severity of the component symptom score.
  
  
  CONCLUSIONS
  Systemic inflammatory response was associated with high symptom burden during the acute phase of AuSCT. Additional research is needed to understand how the inflammatory response is mechanistically associated with symptom expression and whether suppression of this response can reduce symptoms without compromising tumor control.
authors.affiliation: Authors' Affiliations: Departments of Symptom Research, Stem Cell Transplantation, Hematopathology, Lymphoma/Myeloma, and Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Xin Shelley
authors.initials: XS
authors.lastname: Wang
authors.forename: Qiuling
authors.initials: Q
authors.lastname: Shi
authors.forename: Nina D
authors.initials: ND
authors.lastname: Shah
authors.forename: Cobi J
authors.initials: CJ
authors.lastname: Heijnen
authors.forename: Evan N
authors.initials: EN
authors.lastname: Cohen
authors.forename: James M
authors.initials: JM
authors.lastname: Reuben
authors.forename: Robert Z
authors.initials: RZ
authors.lastname: Orlowski
authors.forename: Muzaffar H
authors.initials: MH
authors.lastname: Qazilbash
authors.forename: Valen E
authors.initials: VE
authors.lastname: Johnson
authors.forename: Loretta A
authors.initials: LA
authors.lastname: Williams
authors.forename: Tito R
authors.initials: TR
authors.lastname: Mendoza
authors.forename: Charles S
authors.initials: CS
authors.lastname: Cleeland
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D060828:Induction Chemotherapy; D018836:Inflammation Mediators / Q000097:blood*; D007958:Leukocyte Count; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000378:metabolism* / Q000628:therapy; D009367:Neoplasm Staging; D012720:Severity of Illness Index; D013997:Time Factors; D014182:Transplantation, Autologous
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators