Prognostic factors and outcomes of severe gastrointestinal GVHD after allogeneic hematopoietic cell transplantation

Abstract

We hypothesized that clinical risk factors could be identified within 2 weeks of onset of severe (stage 3 or 4) acute gut GVHD for identifying a patient population with a very poor outcome. Among 1,462 patients who had allogeneic hematopoietic cell transplantation (HCT) between January 2000 and December 2005, 116 (7.9%) developed stage 3–4 gut GVHD. The median time to onset of stage 3–4 gut GVHD was 35 (4–135) days after allogeneic HCT. Eighty-five of the 116 patients (73%) had corticosteroid-resistance before or within 2 weeks after the onset of stage 34 gut GVHD. Significant risk factors for mortality included corticosteroid-resistance (HR=2.93; p=0.0005), age >18 years (HR=4.95; p=0.0004), increased serum bilirubin (HR 2.53; p=0.0001), and overt gastrointestinal bleeding (HR 2.88; p=0.0004). Among patients with stage 3–4 gut GVHD, the subgroup with 0, 1 or 2 risk factors had a favourable prognosis, whereas the subgroup with 3 or 4 risk factors had a dismal prognosis. This information should be considered in designing future studies of severe gut GVHD and in counseling patients about prognosis.

How I treat acute graft-versus-host disease of the gastrointestinal tract and the liver

“…Persistent jaundice is an independent predictor of GVHDrelated mortality. 14,19 Although anecdotal evidence suggests that some immune suppressive regimens for treatment of liver GVHD result in resolution more frequently that other regimens (pulse cyclophosphamide or extracorporeal photopheresis (ECP) or switching from one calcineurin inhibitor to another or sirolimus or oral budesonide), data from controlled trials are lacking. As with GVHD-caused gut ulceration, there appears to be a defect in epithelial regeneration of small bile ducts.…”

“…[14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] In upper-gut GVHD, edematous mucosa is often more impressive than histologic changes. 4 More severe cases are characterized by erythema, friability, and erosions in the pyloric gland area, often accompanied by a pool of bile and retained food in the stomach.…”

BATF-dependent IL-7RhiGM-CSF+ T cells control intestinal graft-versus-host disease

“…The overall outcome of allo-HCT is largely determined by the frequency of relapses of the malignant disorder and the severity of infection-or graft-versus-host disease-associated (GVHD-associated) complications (1)(2)(3). Especially severe forms of intestinal GVHD are associated with high mortality rates (4). Donor T cells have been shown to critically promote inflammation that induces fatal GVHD-associated tissue damage manifesting, for example, in the gut (intestinal GVHD) (1,3).…”

Plasma biomarkers of acute GVHD and nonrelapse mortality: predictive value of measurements before GVHD onset and treatment

“…3 Recognition of the ultimate severity of GVHD often becomes apparent within the first 2 weeks of the onset of signs and symptoms, marked by the absence of improvement during initial prednisone therapy and the development of gastrointestinal mucosal necrosis and jaundice. 4,5 In patients with these adverse prognostic signs, secondary immune suppressive therapy provides suboptimal benefit, and mortality rates are high. 5,6 If it were possible to predict the ultimate severity of GVHD before or at the onset of symptoms, preemptive immune suppressive therapy could be administered in an effort to blunt the intensity of tissue damage, especially in the gastrointestinal tract.…”

“…4,5 In patients with these adverse prognostic signs, secondary immune suppressive therapy provides suboptimal benefit, and mortality rates are high. 5,6 If it were possible to predict the ultimate severity of GVHD before or at the onset of symptoms, preemptive immune suppressive therapy could be administered in an effort to blunt the intensity of tissue damage, especially in the gastrointestinal tract. 2,7 Research on the predictive value of plasma biomarkers has yielded several candidate analytes that have been measured at higher levels in patients with GVHD than in allografted controls with no GVHD or less severe GVHD.…”