Poorer Outcomes Associated With Recurrent aGVHD Warrant Independent Recognition, Says Study

Researchers are urging for independent recognition of recurrent acute graft-versus-host disease (RaGVHD), which they say may be significantly associated with the chronic form of the disease as well as have an impact on survival.

Their warning comes from a study of 200 patients, which showed that recurrence of aGVHD was associated with poorer transplantation outcomes. Among the patients included in the study were those with RaGVHD, those with 1 episode of aGVHD, and those with no aGVHD following T-cell-replete haploidentical hematopoietic cell transplantation without posttransplantation cyclophosphamide.

After a median follow-up of 535 days, analysis showed that RaGVHD carried several implications for survival across the study, leading the researchers to call for further risk stratification of aGVHD. Recurrence of the disease was identified as a risk factor for nonrelapse mortality (NRM)—a primary endpoint—and was significantly associated with both overall survival and disease-free survival.

“Our results suggested that the NRM of patients with RaGVHD was higher compared with those without aGVHD and those with only one episode of aGVHD, regardless of aGVHD grades,” explained the researchers. “The proportional hazards model proved that RaGVHD was an independent predictor for NRM (HR 3.2, p <0.001). Therefore, this study stratified the significantly negative impact of RaGVHD on NRM instead of the original aGVHD.”

According to the researchers, patients with grade 2-3 aGVHD who did not respond to steroid treatment at day 28 were 2.78 times more likely to have an inferior 2-year NRM than patients who achieved a complete or partial response. However, notably, patients who achieved a complete response were still at a risk of developing RaGVHD.

Across the other primary endpoint—composite GVHD endpoints—the researchers found that RaGVHD was associated with worse outcomes, with both inferior GVHD relapse-free survival (HR, 1.9; 95% CI, 1.1-3.3, P = .020) and chronic GVHD relapse-free survival (HR, 2.1; 95% CI, 1.2-3.5, P = .007). Recurrence of aGVHD was the only risk factor independently associated with chronic GVHD (HR, 2.5; 95% CI, 1.4-4.5, P = .003).

Throughout the study, RaGVHD, which was reported in 45 patients accounting for 50 episodes, occurred a median of 91.5 days following transplantation, although the researchers noted the number may actually have been higher.

“It should be noted that the incidences of RaGVHD might be underestimated in this study. In clinical practice, RaGVHD is considered simply as the reappearance of aGVHD signs. Symptom assessment without considering the impact of treatment may lead to the inconsistencies and confusions in RaGVHD evaluation,” detailed the group. “We excluded DLI-induced RaGVHD and RaGVHD in which the steroid for treatment of the previous aGVHD was ≥ 10% of the initial dose. Exclusion of these patients reduced the potential confounding receipt of DLI.”

Among the patients who developed RaGVHD, there were no differences on outcomes based on occurrence prior to or after 100 fays following transplantation. The risk of RaGVHD was strongest for female donors with male recipients (HR, 2.5; P = .009).

Reference

Peng B, Dou L, Yang J, et al. Increased risk of nonrelapse mortality post T-cell-replete haploidentical stem cell transplantation in patients with recurrence of acute graft-versus-host disease. Hematol Oncol. Published online April 6, 2022. doi:10.1002/hon.2999