Time to first flare-up episode of GVHD can stratify patients according to their prognosis during clinical course of progressive- or quiescent-type chronic GVHD

Abstract

GVHD-specific survival (GSS) has been investigated as a potential study end point to describe the clinical course and outcome of chronic GVHD (cGVHD). However, reaching this end point requires a long observation time. We hypothesized that the time to the first flare-up (FFU) of cGVHD (TTF) can be an alternative statistical end point to GSS. This retrospective study included 96 patients with a diagnosis of cGVHD from a cohort of 119 patients with a prior history of acute GVHD. The median TTF was 73 days after the diagnosis of cGVHD. The 2-year cumulative incidences of first, second and third episodes of flare-up (FU) during courses of cGVHD were estimated as 69.5, 46.4 and 22.1%. Those patients who did not have an episode of FU of cGVHD had 96.0% of 2-years GSS rate, while those with 1 and X2 episodes had 50.8 and 46.8%, respectively (P ¼ 0.001). Shorter TTF was associated with poor GSS and decreased overall survival. The shorter TTF during the course of cGVHD was significantly associated with extensive cGVHD (P ¼ 0.002), Hopkins' risk category (P ¼ 0.022) and progressive-type cGVHD (Po0.001) in multivariate analysis. We propose that TTF can be an alternative end point to GSS in cGVHD trials.

Treatment Change as a Predictor of Outcome among Patients with Classic Chronic Graft-versus-Host Disease

“…Our results confirmed those reported by Kim et al 11 in demonstrating that exacerbation of chronic GVHD is associated with an increased risk of non-relapse mortality and with decreased overall survival. As in the Korean study, the associations with non-relapse mortality and survival endpoints are stronger for early exacerbation than for late exacerbation.…”

“…Kim et al 11 recently proposed that an early flare or exacerbation of chronic GVHD could be used as an endpoint in clinical trials. Early flare was strongly associated with decreased GVHD-specific survival, i.e., increased non-relapse mortality.…”

“…GVHD-specific survival at 2 years was 96% among 27 patients who had no flare, 65% among 34 patients with a first flare more than 78 days after diagnosis of chronic GVHD, and 33% among 35 patients who had a first flare within 78 days after diagnosis. 11 Prompted by this report, we reviewed outcomes among patients with chronic GVHD at our center in an effort to validate these results and to assess the utility of early flare as a surrogate for survival in clinical trials.…”

Clinical significance of subcategory and severity of chronic graft-versus-host disease evaluated by National Institutes of Health consensus criteria

“…Given that nearly all patients who developed overlap syndrome had a prior history of aGVHD in our study cohort, NIH overlap syndrome in most instances could be considered as a flare of preexisting aGVHD, concomitant with development of classic cGVHD. In this context, it is important to note that early flare of cGVHD or early treatment change for exacerbation of cGVHD has been reported to be associated with increased NRM and inferior cGSS [34,35]. It is also of note that a significantly higher proportion of patients with overlap syndrome had thrombocytopenia less than 100 9 10 3 /lL at cGVHD onset in our study.…”

Failure-free survival in a prospective cohort of patients with chronic graft-versus-host disease

“…9,10 We also demonstrated that addition of a new treatment was associated with higher non-relapse and overall mortality, which is in agreement with previous studies. 15,16 Inamoto et al published two analyses of FFS in patients who received first-line 9 or second-line 10 therapy for chronic GVHD at a single institution. The median duration of FFS and the rates of FFS at 6 months and 2 years in the current study are similar to their results 9,10 despite the differences in cohort definition.…”