Upper gastrointestinal acute graft-versus-host disease adds minimal prognostic value in isolation or with other graft-versus-host disease symptoms as currently diagnosed and treated

Abstract

Upper gastrointestinal acute graft-versus-host disease is reported in approximately 30% of hematopoietic stem cell transplant recipients developing acute graft-versus-host disease. Currently classified as Grade II in consensus criteria, upper gastrointestinal acute graft-versus-host disease is often treated with systemic immunosuppression. We reviewed the Center for International Blood and Marrow Transplant Research database to assess the prognostic implications of upper gastrointestinal acute graft-versus-host disease in isolation or with other acute graft-versus-host disease manifestations. 8567 adult recipients of myeloablative allogeneic hematopoietic stem cell transplant receiving T-cell replete grafts for acute leukemia, chronic myeloid leukemia or myelodysplastic syndrome between 2000 and 2012 were analyzed. 51% of transplants were from unrelated donors. Reported upper gastrointestinal acute graft-versus-host disease incidence was 12.1%; 2.7% of recipients had isolated upper gastrointestinal acute graft-versus-host disease, of whom 95% received systemic steroids. Patients with isolated upper gastrointestinal involvement had similar survival, disease-free survival, transplant-related mortality, and relapse as patients with Grades 0, I, or II acute graft-versus-host disease. Unrelated donor recipients with isolated upper gastrointestinal acute graft-versus-host disease had less subsequent chronic graft-versus-host disease than those with Grades I or II disease (P=0.016 and P=0.0004, respectively). Upper gastrointestinal involvement added no significant prognostic information when present in addition to other manifestations of Grades I or II acute graft-versus-host disease. If upper gastrointestinal symptoms were reclassified as Grade 0 or I, 425 of 2083 patients (20.4%) with Grade II disease would be downgraded, potentially impacting the interpretation of clinical trial outcomes. Defining upper gastrointestinal acute graft-versus-host disease as a Grade II entity, as it is currently diagnosed and treated, is not strongly supported by this analysis. The general approach to diagnosis, treatment and grading of upper gastrointestinal symptoms and their impact on subsequent acute graft-versus-host disease therapy warrants reevaluation.

Sole Upfront Therapy with Beclomethasone and Budesonide for Upper Gastrointestinal Acute Graft-versus-Host Disease

“…A recent analysis of the Center for International Blood and Marrow Transplant Research database did not show a significant prognostic impact of UGI aGVHD on transplantationrelated outcomes [29]. According to the Minnesota aGVHD risk classification, all patients in our present study cohort would be classified as standard risk [34,35].…”

“…To the best of our knowledge, there are no data on the role of BDP alone or BDP+BUD in this setting. Patients with UGI disease often progress to symptomatic lower GI (LGI) involvement [20,[29][30][31]. Whereas BDP reaches the esophagus and stomach but not beyond the duodenum, BUD is released from capsules in the stomach, percolates the ileum and reaches the colon, where it is partly reabsorbed.…”

Small crystals with severe consequences

“…Acute GvHD occurs in up to 50% of patients after SCT and primarily affects the GI tract, liver and skin [ 11 ]. Up to 12% of GvHD cases involve the upper GI tract [ 12 ] but histopathology ruled out GvHD as the cause of pneumatosis in our case. Symptoms of GI tract infection and elevated liver enzyme and bilirubin levels can also be a sign of cytomegaly virus (CMV) infection, which occurs in up to 30% of patients after SCT [ 13 ].…”

Retinoic acid–responsive CD8 effector T cells are selectively increased in IL-23–rich tissue in gastrointestinal GVHD

“…Importantly, we validated the accuracy of this approach by demonstrating close correlation between frequencies of cells enumerated with the sequential immunostaining pipeline and manual counting approach with frequencies of cells enumerated with single-stain IHC and automated counting, We studied patient biopsies from both the upper and lower GI-tract although most patients had biopsies from either just the lower GI-tract or from both sites. Although studies have shown that lower GI-GvHD has a more significant impact than upper GI-GVHD on GvHD-related mortality, 32 upper GI pathology may increase lower GI-GvHD symptoms. 33 Importantly, although numbers of RA-responsive cells in lower GI-biopsies were more closely associated with clinical severity of GI-GvHD than numbers in upper GI-biopsies, we found an increase in RA-responsive cells in both upper and lower GI-biopsies supporting a pathogenic role for RAresponsive cells throughout the GI-tract.…”