Acute GVHD Diagnosis and Adjudication in a Multicenter Trial: A Report From the BMT CTN 1202 Biorepository Study.

TitleAcute GVHD Diagnosis and Adjudication in a Multicenter Trial: A Report From the BMT CTN 1202 Biorepository Study.
Publication TypeJournal Article
Year of Publication2021
AuthorsReshef, R, Saber, W, Bolaños-Meade, J, Chen, G, Bin Chen, Y-, Ho, VT, Ponce, DM, Nakamura, R, Martens, MJ, Hansen, JA, Levine, JE
JournalJ Clin Oncol
Date Published2021 06 10
KeywordsAdolescent, Adult, Aged, Child, Child, Preschool, Clinical Trials as Topic, Databases, Factual, Female, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Humans, Incidence, Infant, Male, Middle Aged, Young Adult

PURPOSE: Accurate and reproducible methods to diagnose, grade, and report acute graft-versus-host disease (GVHD) are critical for the evaluation of therapies and biomarkers.

PATIENTS AND METHODS: The Blood and Marrow Transplant Clinical Trials Network 1202 study is an observational study of 1,709 allogeneic hematopoietic cell transplantation recipients that implemented weekly data reporting and near real-time data adjudication by an end point review committee (ERC), assigning a confidence level (confirmed, probable, possible, or negative) to the diagnosis of acute GVHD at onset.

RESULTS: During the first 100 days, symptoms consistent with GVHD developed in 90% of cases but were often determined by centers to be due to causes other than GVHD. Indeed, GVHD was under consideration in only 23% of cases at symptom onset. Diagnostic biopsies were obtained in 40% of cases, but treatment often was incongruous with biopsy findings and 10.5% of biopsies were equivocal. Importantly, more than 40% of steroid courses were started for reasons other than GVHD. The ERC modified the determination of GVHD diagnosis and/or grade in 12.3% of onset cases. The cumulative incidence of acute GVHD as reported by the centers was 62%. When the ERC adjudicated GVHD onset to be present only if the confidence level was probable or confirmed, the incidence of GVHD declined to 49%.

CONCLUSION: This study demonstrates that the incidence of GVHD may be overestimated at symptom onset, establishes a contemporary benchmark for acute GVHD, and suggests a structured framework for reporting and adjudication of GVHD that could be used in prospective trials.

Alternate JournalJ Clin Oncol
PubMed ID33507810
PubMed Central IDPMC8260916
Grant ListU10 HL069294 / HL / NHLBI NIH HHS / United States
UG1 HL069249 / HL / NHLBI NIH HHS / United States
UG1 HL138645 / HL / NHLBI NIH HHS / United States
U24 CA076518 / CA / NCI NIH HHS / United States
U24 HL138660 / HL / NHLBI NIH HHS / United States