Table 3

Variables at or before the symptomatic onset of gastrointestinal GVHD that are more common in patients whose GVHD will run a more severe course

VariableComments
Unrelated donor (HLA mismatched > matched) Less likely to respond to initial therapy than patients with related or cord blood donors12  
Diarrheal volume Greater volume correlates with refractoriness to initial treatment with prednisone.6,12  
Total serum bilirubin Worse outcome with total serum bilirubin increase from 1 to 3 mg/dL or when jaundice is present at GVHD onset12,14-17  
Serum albumin change Abrupt fall of serum albumin ≥0.5 g/dL before onset of symptoms predicts grade 3 to 4 GVHD in patients who received reduced-intensity conditioning.10  
Fecal α-1 antitrypsin Measures a luminal protein that cannot be digested by proteolytic enzymes; reflects gut protein loss8,9  
Fecal calprotectin Calcium-binding protein in neutrophils; reflects neutrophilic mucosal inflammation in inflammatory bowel disease and gut GVHD 
Skin changes More extensive skin GVHD is a predictor of severity and need for higher doses of prednisone.12,18  
Endoscopic findings Ulceration and sloughing of mucosa6,19  
Mucosal histologic findings Infiltrating neutrophils16  
Increased apoptotic cells16  
Increased eosinophils20  
Low Paneth cell numbers21  
Crypt loss22  
Ulceration 
Pericapillary hemorrhage23  
Serum biomarkers Increased levels with more severe GVHD: TIM3, sTNFR1, ST2, IL-6, Reg3α24-29  
Endothelial markers Loss of thrombomodulin expression in gut mucosal biopsies30  
Increased blood levels of angiopoietin-231  
Changes in circulating angiogenic factors32  
VariableComments
Unrelated donor (HLA mismatched > matched) Less likely to respond to initial therapy than patients with related or cord blood donors12  
Diarrheal volume Greater volume correlates with refractoriness to initial treatment with prednisone.6,12  
Total serum bilirubin Worse outcome with total serum bilirubin increase from 1 to 3 mg/dL or when jaundice is present at GVHD onset12,14-17  
Serum albumin change Abrupt fall of serum albumin ≥0.5 g/dL before onset of symptoms predicts grade 3 to 4 GVHD in patients who received reduced-intensity conditioning.10  
Fecal α-1 antitrypsin Measures a luminal protein that cannot be digested by proteolytic enzymes; reflects gut protein loss8,9  
Fecal calprotectin Calcium-binding protein in neutrophils; reflects neutrophilic mucosal inflammation in inflammatory bowel disease and gut GVHD 
Skin changes More extensive skin GVHD is a predictor of severity and need for higher doses of prednisone.12,18  
Endoscopic findings Ulceration and sloughing of mucosa6,19  
Mucosal histologic findings Infiltrating neutrophils16  
Increased apoptotic cells16  
Increased eosinophils20  
Low Paneth cell numbers21  
Crypt loss22  
Ulceration 
Pericapillary hemorrhage23  
Serum biomarkers Increased levels with more severe GVHD: TIM3, sTNFR1, ST2, IL-6, Reg3α24-29  
Endothelial markers Loss of thrombomodulin expression in gut mucosal biopsies30  
Increased blood levels of angiopoietin-231  
Changes in circulating angiogenic factors32  

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