The objective of this study was to prospectively assess the relationship between symptom severity and changes in inflammatory cytokines around the time of diagnosis of acute GVHD in AML/MDS patients during the first 100 days of allo-BMT. Methods: Weekly symptom assessment with the M. D. Anderson Symptom Inventory was done for 30 patients over time of BMT. A panel of inflammatory cytokines (IL-1ra, IL-6, IL-8, IL-10, IL-12, TNF-a) was assayed at multiple time points (pre BMT, conditioning, BMT day, Day 1, nadir, Day 7, 14, 21, 28, 60, 90–100, also including days 1, 3, 5, 10 and 15 after diagnosis of a GVHD for the 26 patients who developed it). Results: Of the 26 patients, 69% had grade 1 GVHD, 27% had grade 2, and 4% had grade 3. 42% were treated with 2mg/kg of steroids, 31% with topical steriods. Figure 1 displays Loess curves that show the multiple symptom pattern for the 26 GVHD patients. These nonspecific symptoms reached their highest levels before the day of diagnosis. Immediate symptom reduction after diagnosis was most likely caused by administration of steroids. The Lowess curves in Figure 2 show the changes in serum cytokines levels pre- and post-GVHD (log based 10). IL-8 was significantly correlated with some symptoms before and after GVHD (Table 1). Conclusion: During development of GVHD in the acute phase of allo-BMT, there is an observed relationship of certain symptom severity and increased or decreased inflammatory cytokine levels in this pilot study. Further study is warranted for a causal link between general sickness and specific cytokines during human GVHD development.

Table 1.

Correlations between symptoms severity and cytokines Levels before and after the Development of GVHD in the First 100 Days after Allo-BMT

 IL-8 
Pre-GVHD  
Shortness of breath r = −0.708, P<.01 
Dry mouth r = 0.667, P<.05 
Sadness r = 0.631, P<.05 
Post-GVHD  
Sleep Disturbance r = 0.564, P<.05 
Drowsiness r = −0.565, P<.05 
Vomiting r = −0.558, P<.05 
 IL-8 
Pre-GVHD  
Shortness of breath r = −0.708, P<.01 
Dry mouth r = 0.667, P<.05 
Sadness r = 0.631, P<.05 
Post-GVHD  
Sleep Disturbance r = 0.564, P<.05 
Drowsiness r = −0.565, P<.05 
Vomiting r = −0.558, P<.05 
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Topics:
bone marrow transplantation, allogeneic, cytokine, graft-versus-host disease, acute, graft-versus-host disease, interleukin-8, steroids, drowsiness, dyspnea, interleukin-10, interleukin-12

Author notes

Corresponding author

2005, The American Society of Hematology
2005
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