The accuracy of acute graft-versus-host disease (GvHD) diagnosis is critical for the evaluation of new treatments and biomarkers.
The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 1202 trial (NCT01879072) aimed to improve the accuracy of acute GvHD diagnosis, minimizing systematic observational errors and reporting errors. To achieve that goal, they proposed:
- Reporting of detailed symptoms in GvHD organs
- High frequency of reporting (i.e., weekly)
- Continuous and prospective adjudication in near-real time (i.e., monthly) by an endpoint review committee (ERC)
- Annotation of GvHD events with conﬁdence levels (possible, probable, or conﬁrmed)
This observational study enrolled 1,709 allogeneic hematopoietic cell transplantation recipients transplanted at U.S. centers from 2013 to 2016. Results from the study, recently reported by Ran Reshef and colleagues in the Journal of Clinical Oncology,1 demonstrated that:
- During the first 100 days posttransplant, about 90% of patients developed symptoms in one or more GvHD target organs. Most frequent symptoms were skin rash, diarrhea, nausea, vomiting, or anorexia, and jaundice
- However, only in 22.6% of cases was GvHD considered as the diagnosis at symptom onset, while the likelihood of GvHD diagnosis increased overtime when additional symptoms appeared, or old symptoms persisted
- Overall, biopsies were performed from GvHD target organs in 40% of patients with suspected GvHD but only in 23% of suspected cases at symptom onset
- While systemic steroid use was frequent in confirmed cases of GvHD, almost 20% of patients with confirmed lower gastrointestinal GvHD and almost 40% of patients with confirmed skin GvHD did not receive systemic steroids
- Furthermore, systemic steroids were administered in 40% of patients with negative biopsy results, and this was declared as GvHD treatment in 62% of these patients
- When GvHD reporting was adjudicated, the Day 100 cumulative incidence of acute GvHD was 13.3% lower than that reported by the centers (48.7% versus 62%)
In conclusion, these results show that GvHD is rarely diagnosed and managed based on the results of biopsy. Furthermore, GvHD may be overestimated at symptom onset. BMT CTN 1202 demonstrated the utility of a new adjudication and reporting system for GvHD that would improve the diagnosis and management of this very serious condition.
Previously, results were presented at the 2019 Transplantation & Cellular Therapy Meetings of ASBMT and CIBMTR, which the GvHD Hub summarized here.