Surprising Results Counter Accepted Belief About Onset of Acute Graft-Versus-Host Disease

Typically, if acute graft-versus-host disease (aGVHD) is going to occur, it will happen before day 100 following an allogeneic hematopoietic cell transplant (HCT). Disease that occurs after day 100 is considered late aGVHD, and it has generally been considered less severe than its classic-onset counterpart.

During the oral session GVHD-Clinical at the 2023 Tandem Meetings of ASTCT and CIBMTR, Dr. Yu Akahoshi presented the results of a study that evaluated the “incidence, clinical outcomes, and impact of biomarkers for late and classic aGVHD in 3542 consecutive adult recipients who received their first HCT at twenty-three Mount Sinai Acute GVHD Consortium (MAGIC) centers between January 1, 2014 and August 31, 2021.”

For the study comparison, aGVHD that occurred between days 1-100 after HCT, including any that persisted or recurred after day 100, was considered classic aGVHD. Any new presentations occurring after day 100 were considered late aGVHD.

Of the total cohort of 3542 consecutive adult recipients, 1601 (45%) developed classic aGVHD, and 256 (7%) developed late aGVHD. After determining cumulative incidence, Akahoshi et al analyzed the effect of either classic or late aGVHD on non-relapse mortality (NRM). The results of their analysis were unexpected.

“Both classic and late aGHVD were associated with an increased risk of NRM (P < 0.001) and, surprisingly, the [hazard ratio] of 4.37 for late aGVHD on NRM was higher than the [hazard ratio] of 2.53 for classic aGVHD,” the team reported.

These surprising results contradict the current belief that late-onset aGVHD is typically less severe. The team concluded that “contrary to expectation, late aGVHD was more severe than classic aGVHD by both clinical and biomarker parameters and was associated with higher NRM.”

Akahoshi Y, Spyrou N, Hogan WJ, et al. De novo late acute GVHD: incidence, outcomes, and impact of biomarkers compared to classic acute GVHD. Abstract #32. Presented at the 2023 Tandem Meetings of ASTCT and CIBMTR; February 15-19, 2023; Orlando, FL.