Acute upper gastrointestinal graft-versus-host disease: clinical significance and response to immunosuppressive therapy

Abstract

Recognized manifestations of acute graft-versus-host disease (GVHD) of the gastrointestinal (GI) tract include secretory diarrhea, abdominal pain, and, at times, hemorrhage. In a review of 469 patients undergoing allogeneic bone marrow transplantation (BMT) from matched sibling donors at our institution, we have recognized a syndrome of upper GI GVHD. This syndrome, presenting clinically as anorexia, dyspepsia, food intolerance, nausea, and vomiting, was recognized and confirmed histologically in 62 patients (13% by Kaplan-Meier projection) at the initiation of systemic GVHD therapy, a subset of the 197 patients developing grade II through IV GVHD. These 62 patients with upper GI GVHD were significantly older than the overall BMT population and older than the cohort with grade II through IV GVHD, as well. Of the 62 patients, 25 had upper GI GVHD accompanied only by limited (stage 1 and 2) skin GVHD; 13 others with upper GI GVHD plus limited skin involvement at initial presentation later progressed to more extensive multiorgan involvement; 24 others presented with upper GI along with other organ GVHD. This upper GI GVHD syndrome, first recognized at our center in 1983, has been diagnosed with increasing frequency (22% +/- 5%) in the most recent 5-year interval. The upper GI GVHD syndrome is more responsive to immunosuppressive therapy than grade II GVHD defined by Seattle criteria, with complete and continuing responses to treatment observed in 71% +/- 17% (95% confidence interval) of those with the upper GI GVHD syndrome compared with only 37% +/- 10% complete responses in other patients with grade II GVHD (P = .002). Patients failing immunosuppressive therapy for upper GI GVHD often progress to symptomatic lower GI involvement, suggesting that this syndrome may be an earlier and perhaps more treatable manifestation of this unique intestinal immunopathology, which is followed by chronic GVHD in 74% of patients. While upper GI GVHD symptoms are nonspecific and require invasive histologic and microbiologic studies to confirm the diagnosis, we believe this syndrome has been underreported after allogeneic BMT and propose its recognition within the clinical GVHD scoring system.

Population pharmacokinetics of unbound mycophenolic acid in adult allogeneic haematopoietic cell transplantation: effect of pharmacogenetic factors

“…Acute GVHD and neutrophil engraftment data were obtained through the University of Minnesota Bone Marrow Transplant Database. GVHD was staged and graded according to the standard University of Minnesota GVHD criteria based on clinical and pathological criteria . Acute GVHD was defined as the day of development of grades II‐IV within day 100 of transplantation.…”

Clinical Factors Predicting the Response of Acute Graft-versus-Host Disease to Corticosteroid Therapy: An Analysis from the GVHD Working Group of the Japan Society for Hematopoietic Cell Transplantation

“…Several studies have evaluated a variety of agents added to prednisone [1][2][3][4][5][6][7], but the use of prednisone or methylprednisolone alone is recommended as a standard first-line treatment for acute GVHD [8]. The response rate is approximately 40% to 60%, and patients unresponsive or resistant to corticosteroid therapy have an increased risk of mortality related to uncontrolled GVHD [2,[9][10][11][12][13][14][15][16]. Some clinical factors are reported to be statistically predictive of a response to systemic corticosteroid therapy: HLAmismatched donor transplantation, unrelated donor transplantation, combination of male recipient and female donor, early onset of GVHD, higher grade of GVHD, and liver or gut involvement of GVHD have lower response rates [2,9,10,14].…”

Acute Graft‐versus‐Host Disease: Emerging Insights and Updates into Detection, Prevention, and Treatment

“…10 This was updated following the Keystone Consensus to the modified Glucksberg or Keystone criteria 20 years later, while at approximately the same time it was compared with yet a third grading tool, the International Bone Marrow Transplant Registry (also referred to as the Center for International Blood and Marrow Transplant Research [CIBMTR]) criteria. 11,12 The development of the Minnesota grading system 11,13,14 came next, with the most recently developed scoring tool published in 2016, the Mount Sinai Acute GVHD International Consortium (MAGIC) criteria (Tables 1 and 2). 15 Initial staging in all five tools is quite similar (Table 1); however, there is variability when determining the maximum grade (Table 2), making interpretation and implementation a challenge.…”