Figure 7.
Low numbers of L cells in the gut and high GLP-2 levels in blood correlate with poor patient outcome after allo-HCT. Sigmoid colonic biopsies from 29 patients with initial diagnosis of acute gastrointestinal GVHD were stained for GLP-1 for quantification of L cells. Median L cell number per crypt was 1.05, therefore 1 L cell per crypt was used as cutoff for stratification in high (≥1 L cell per crypt) and low L-cell counts. (A) The 2-year cumulative incidence of NRM in patients with low vs high L-cell counts. (B) Cumulative incidence of SR-GVHD at 6 months in patients with low vs high L-cell counts. (C) Representative immunohistochemistry stain images of colonic biopsies stained for GLP-1 (brown). Left, patient with high L-cell count who responded well to steroid treatment and stayed alive. Right, patient with low L-cell count who developed SR-GVHD and NRM. For GLP-2 blood-level correlation, serum prepared from fasting blood samples of 82 consecutive patients with newly diagnosed acute GVHD was analyzed for GLP-2 concentration. Median GLP-2 concentration was 3.7 ng/mL, which was used as cutoff for stratification in high (>3.7 ng/mL) and low GLP-2 levels. (D) Cumulative incidence of SR acute GVHD at 6 months in patients with high vs low serum GLP-2 concentrations. (E) Cumulative incidence of NRM at 2 years in patients with high vs low serum GLP-2 concentrations. GLP-2 level in the peripheral blood as a continuous variable was also associated with a higher risk of SR-GVHD (HR, 1.09; 95% CI, 1.00-1.19; P = .05) and NRM (HR, 1.17; 95% CI, 1.03-1.32; P = .01). (F) Further subgroup analysis was performed including only patients with no gastrointestinal symptoms at time of diagnosis of GVHD (n = 53). Cumulative incidence of SR-GVHD at 6 months again tended to be higher for patients with high GLP-2 levels: 54% (95% CI, 34% to 74%) vs 26% (95% CI, 8% to 44%), P = .05. (G) Cumulative incidence of NRM at 2 years was higher for patients with high GLP-2 concentrations: 40% (95% CI, 20% to 60%) vs 4% (95% CI, 0% to 12%) (P = .002).

Low numbers of L cells in the gut and high GLP-2 levels in blood correlate with poor patient outcome after allo-HCT. Sigmoid colonic biopsies from 29 patients with initial diagnosis of acute gastrointestinal GVHD were stained for GLP-1 for quantification of L cells. Median L cell number per crypt was 1.05, therefore 1 L cell per crypt was used as cutoff for stratification in high (≥1 L cell per crypt) and low L-cell counts. (A) The 2-year cumulative incidence of NRM in patients with low vs high L-cell counts. (B) Cumulative incidence of SR-GVHD at 6 months in patients with low vs high L-cell counts. (C) Representative immunohistochemistry stain images of colonic biopsies stained for GLP-1 (brown). Left, patient with high L-cell count who responded well to steroid treatment and stayed alive. Right, patient with low L-cell count who developed SR-GVHD and NRM. For GLP-2 blood-level correlation, serum prepared from fasting blood samples of 82 consecutive patients with newly diagnosed acute GVHD was analyzed for GLP-2 concentration. Median GLP-2 concentration was 3.7 ng/mL, which was used as cutoff for stratification in high (>3.7 ng/mL) and low GLP-2 levels. (D) Cumulative incidence of SR acute GVHD at 6 months in patients with high vs low serum GLP-2 concentrations. (E) Cumulative incidence of NRM at 2 years in patients with high vs low serum GLP-2 concentrations. GLP-2 level in the peripheral blood as a continuous variable was also associated with a higher risk of SR-GVHD (HR, 1.09; 95% CI, 1.00-1.19; P = .05) and NRM (HR, 1.17; 95% CI, 1.03-1.32; P = .01). (F) Further subgroup analysis was performed including only patients with no gastrointestinal symptoms at time of diagnosis of GVHD (n = 53). Cumulative incidence of SR-GVHD at 6 months again tended to be higher for patients with high GLP-2 levels: 54% (95% CI, 34% to 74%) vs 26% (95% CI, 8% to 44%), P = .05. (G) Cumulative incidence of NRM at 2 years was higher for patients with high GLP-2 concentrations: 40% (95% CI, 20% to 60%) vs 4% (95% CI, 0% to 12%) (P = .002).

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