TCT Meeting 2019 | A report from the BMT CTN 1202 biorepository trial: Acute graft-versus-host disease diagnosis and adjudication

On 23 February 2019 at the 2019 TCT Transplantation and Cellular Therapy Meetings of ASBMT and CIBMTR in Houston, Texas, USA, Ran Reshef from Columbia University Medical Center, New York, NY, USA, presented the findings of the BMT CTN 1202 biorepository study evaluating graft-versus-host disease (GvHD) biomarkers and other transplant outcomes.

Patients and methods

• BMT CTN 1202 created a biorepository and clinical data bank for the study
• The final repository included 41,468 annotated biospecimens from 1709 alloHCT patients (pts) transplanted at U.S. centers from 2012-2016
• Symptoms suggestive of GvHD, biopsy results, immunosuppressive medications, and possible etiologies were reported weekly until day 100
• An end-point review committee (ERC) performed a near real-time adjudication of reported symptoms at their onset and assigned a confidence level (Confirmed, Probable, Possible or Negative) for each organ according to Harris, BBMT, 2016
• only 23% of cases and GvHD was considered the only etiology in 12%.
• Biopsies (bx) were performed in 40% of pts, most often for upper or lower GI symptoms
• Bxresults were equivocal in 11% although the range among centers was broad (0-45%). Equivocal results were most likely for skin bx and during the 2^nd week after transplant
• Systemic steroids were administered to 70% of pts at least once, often for non-GvHD reasons (41% of steroid courses)
• When GvHD was in the differential diagnosis, systemic steroids were started 81% of the time

 Key findings

• The ERC adjudicated 2,008 cases with symptoms suggestive of GvHD onset
• 12.3% of cases the ERC modified either the center reported diagnosis of GvHD (4.6%) or the automated generated severity grade (7.7%)
• GvHD was diagnosed in 1025 pts and categorized as confirmed (31%), probable (50%), or possible (19%)
• The proportion of definitive diagnoses increased with longer time post-transplant
• ERC adjudication substantially lowered the incidence of GvHD grade 2-4 from 30% as reported by centers to 23% (confirmed or probable) by ERC
• An adjudicated diagnosis of GvHD strongly associated with 6 month NRM, adjusted for patient age, gender and HLA matching (HR=2.0, P <0.001)
• Adjudicated GvHD grade was also strongly associated with 6 month NRM (Grade 2, HR=2.1, P <0.001; Grade 3-4, HR=7.1, P <0.001)

Conclusion

In conclusion, this is the largest prospective observational study of GvHD outcomes. The findings showed that symptoms in involved organs seem general after transplant, their differential diagnosis is wide, tissue biopsies are irregularly performed, and steroids are often administered for reasons other than acute GvHD. Dr. Reshef added that “these limitations undermine the current methods of diagnosis and reporting of acute GvHD on clinical trials. A robust reporting and adjudication system has significant value and may improve the chances of success of prospective clinical trials.”