Significantly worse survival of patients with NIH-defined chronic graft-versus-host disease and thrombocytopenia or progressive onset type: results of a prospective study

Abstract

Chronic graft-versus-host disease (GVHD) remains a serious complication after allogeneic hematopoietic stem cell transplantation (HCT). In 2005 the National Institutes of Health (NIH) established new criteria for chronic GVHD based on retrospective data and expert recommendations. We prospectively evaluated the incidence of NIH-defined chronic GVHD and its prognostic impact in 178 consecutive patients. The cumulative incidence of chronic GVHD at 3 years was 64, 48 and 16% for chronic classic GVHD and overlap syndrome. Prior acute GVHD and myeloablative conditioning were significantly associated with increased risk of chronic GVHD. Three-year survival (overall survival (OS)) for late-acute GVHD, chronic classic and overlap chronic GVHD when assigned on day 100 were 69, 83 and 73%. OS was significantly worse for patients with platelet counts below 100 g/l at onset of chronic GVHD (35% versus 86%, Po0.0001) and progressive as compared with de novo and quiescent onset of chronic GVHD (54.5% versus 89.5% versus 84%, P ¼ 0.022 and 0.001). Peak severity of chronic GVHD had no impact on non-relapse mortality (NRM) and OS. Recurrent acute GVHD, platelet counts below 100 g/l at diagnosis of chronic GVHD, progressive onset of chronic GVHD and advanced disease stage prior to HCT were significantly associated with increased NRM. This prospective analysis provides for the first-time data on the incidence rates of NIHdefined chronic GVHD categories and identified risk factors for the occurrence of chronic GVHD. A prognostic value of thrombocytopenia and progressive onset type of chronic GVHD for survival after HCT was observed in NIH-defined chronic GVHD.

Risk factors and organ involvement of chronic GVHD in Japan

“…The impact of quiescent onset chronic GVHD has been controversial, 2,33 but chronic GVHD-specific survival in the patients showing quiescent onset chronic GVHD was almost comparable to those showing de novo onset in line with several recent reports. 5,34 Although oral involvement was not associated with lower chronic GVHD-specific survival, which is compatible with a previous report, 35 intestinal or genital involvement was associated with lower survival rate. The use of U-CB was not associated with chronic GVHD-specific survival, even when only patients with extensive chronic GVHD were considered (data not shown).…”

Association of severity of organ involvement with mortality and recurrent malignancy in patients with chronic graft-versus-host disease

“…[10][11][12][13] We extended these findings by taking the dynamic changes in chronic GVHD severity into account, which mirrors the clinical reality of episodic improvement and worsening over time. Hazard analysis confirmed that the NIH global score correlated well with mortality rates regardless of time since initial treatment, suggesting that the NIH global score is applicable to patients throughout the course of the disease after initial treatment.…”

“…9 Although the NIH global score was developed through expert opinion, several studies have shown that the global score at onset of chronic GVHD is associated with risk of subsequent mortality. [10][11][12][13] Many issues do, however, remain to be determined. (i) Since the NIH global score was based on expert opinion and was not originally intended to predict mortality, does this score provide an optimal model for predicting mortality risk in patients with chronic GVHD?…”

Chronic GVHD: Where are we? Where do we want to be? Will immunomodulatory drugs help?

“…8,16,17 Several retrospective and prospective analyses identified additional prognostic variables which complement the NIH consensus staging system including low platelet levels, poor performance score when cGVHD is diagnosed, and gastrointestinal tract involvement which significantly influence outcome and progressive onset type of cGVHD as adversely affecting survival. 18,19 These correlations need confirmation. cGVHD is a multiorgan alloimmune and autoimmune disorder characterized by immune dysregulation, immune deficiency, impaired end-organ function and decreased survival.…”