The prognostic impact of upper gastrointestinal acute graft-versus-host disease 

Previous studies have shown that upper gastrointestinal acute graft-versus-host disease (UGI aGvHD) is presented in approximately 30% of cases with aGvHD. The prognostic value and staging for UGI aGvHD in isolated cases or with other aGvHD manifestations have not been studied in a large multi-center cohort yet. Therefore, Sarah Nikiforow from Dana-Farber Cancer Institute, Boston, MA, USA, and colleagues conducted a retrospective study to analyze the prognostic effects of UGI aGvHD. Data was collected from the Center for International Blood and Marrow Transplant Research (CIBMTR) database. The results of the study were published ahead of print in Haematologica.

The primary endpoint of the study was overall survival (OS). Secondary endpoints were treatment-related mortality (TRM), relapse rate, disease-free survival (DFS), and incidence of chronic GvHD (cGvHD).

Patient characteristics:

• N = 8,567 adult patients
• Median age = 42 years (range, 18–72)
• All patients underwent myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) between 2000 and 2012
• Unrelated donor recipients: 51%
• Indications: AML/MDS (60%), ALL (21%), and CML (18%)
• Incidence of UGI aGvHD: 229 patients (12.1%)
• Incidence of isolated UGI aGvHD: 2.7% (systemic steroids were administered for 95% of patients)

Key findings:

Median follow-up: 71 months (range, 1–173)

• 1-year OS: 62%
• 1-year DFS: 52%
• 1-year relapse rate: 29%
• 100–day TRM: 11%
• 1-year incidence of cGvHD: 43%
• Grades II–IV aGvHD rates: 35.6% for MRD vs 52.6% for URD recipients
• Patients receiving unrelated donor transplant with isolated UGI aGvHD were less likely to have subsequent cGvHD than patients with grades I or II GvHD, P = 0.016 and P = 0.0004, respectively
• Percentage of patients receiving systemic steroids: 79.8% of patients with maximum grade I (skin-only) disease vs 95.4% of patients with iUGI plus stage I or II skin disease (grade II) vs 91.6% of patients with UGI symptoms plus stage I or II skin disease (grade II)
• Analysis of aGvHD patients: patients with UGI aGvHD and patients with grades I or II aGvHD without UGI: there were no significant differences in OS, DFS, relapse, or transplant-related mortality
• Prognostic impact of UGI aGvHD symptoms with other manifestations: OS, DFS, TRM, or relapse were not significantly different in aGvHD patients with or without UGI symptoms
• If grade II UGI aGvHD were reclassified, 20.4% of patients (425/2083) would be classified as grade 0 or I

This study indicates that UGI aGvHD as it is currently diagnosed as grade II aGvHD, due to the consensus criteria, has numerous limitations and needs to be revised in terms of diagnosis, treatment and grading. The authors stated that reclassification of patients with UGI GvHD as grade I “could be considered, with grade I aGvHD generally considered to have few prognostic implications.”

The study group further added that they “would recommend highly standardized prospective trials involving endoscopic biopsies to explore whether system steroid therapy is required for these symptoms in isolation or with grade I skin-only aGvHD.”