Development of a prognostic model for grading chronic graft-versus-host disease

Abstract

The disease-specific survival (DSS) of 151 patients with chronic graft-versushost disease (cGVHD) was studied in an attempt to stratify patients into risk groups and to form a basis for a new grading of cGVHD. The data included the outcome and 23 variables at the diagnosis of cGVHD and at the primary treatment failure (PTF). Eighty-nine patients (58%) failed primary therapy for cGVHD. Nonrelapse mortality was 44% after a median follow-up of 7.8 years. The probability of DSS at 10 years after diagnosis of cGVHD (DSS1) and after PTF (DSS2) was 51% (95% confidence interval [CI] ‫؍‬ 39%, 60%) and 38% (95% CI ‫؍‬ 28%, 49%), respectively. According to multivariate analysis, extensive skin involvement (ESI) more than 50% of body surface area; hazard ratio (HR) of 7.0 (95% CI ‫؍‬ 3.6-13.4), thrombocytopenia (TP) (< 100 000/L; HR, 3.6; 95% CI ‫؍‬ 1.9-6.8), and progressivetype onset (PTO) (HR, 1.7; 95% CI ‫؍‬ 0.9-3.0) significantly influenced DSS1. These 3 factors and Karnofsky Performance Score of less than 50% at PTF were significant predictors for DSS2. The DSS1 at 10 years for patients with prognostic factor score (PFS) at diagnosis of 0 (none), less than 2 (ESI only or TP and/or PTO), 2 to 3.5 (ESI plus either TP or PTO), and more than 3.5 (all 3 factors) was 82%, 68%, 34%, and 3% (P ‫؍‬ .05, < .001, < .001), respectively. The DSS2 at 5 years for patients with PFS at PTF of 0, 2 or less, 2 to 3.5, and more than 3.5 were 91%, 71%, 22%, and 4% (P ‫؍‬ .2, .005, and < .001), respectively. It was concluded that these prognostic models might be useful in grouping the patients with similar outcome. (Blood. 2001;97:1219-1226)

Graft‐versus‐host disease (GVHD)‐specific survival and duration of systemic immunosuppressive treatment in patients who developed chronic GVHD following allogeneic haematopoietic cell transplantation

“…Progressive presentation and thrombocytopenia were important risk factors for death in several studies (Sullivan et al, 1988a;Wingard et al, 1989;Akpek et al, 2001), but not in other studies (Lee et al, 2002), including this study. No consensus has been reached regarding prognostic factors for survival in patients with chronic GVHD.…”

“…Infection is the frequent cause of death in patients with chronic GVHD, but leukaemia relapse, which is not directly related to GVHD, is another major cause of death in these patients (Wagner et al, 2000;Akpek et al, 2001). Thus GSS seems to be a more appropriate endpoint for assessing the effects of GVHD alone on patient survival.…”

“…Aside from extensive chronic GVHD categorized by the current dichotomous staging system, poor performance status , thrombocytopenia (Sullivan et al, 1988a), progressive presentation, lichenoid changes on skin histology, elevation of serum bilirubin (Wingard et al, 1989) and extensive skin involvement (Akpek et al, 2001) have been reported to have an adverse prognostic impact upon the survival of patients with chronic GVHD. In the statistical analysis of most studies, all deaths were defined as an event whether or not they were directly related to chronic GVHD.…”

“…In the statistical analysis of most studies, all deaths were defined as an event whether or not they were directly related to chronic GVHD. Recently, Akpek et al (2001) developed a prognostic model for predicting chronic GVHD-specific survival (GSS) in which deaths solely due to relapse were not considered an event. Considering that a proportion of the patients with chronic GVHD died because of succumbing to an underlying disease, GSS seems to be a more appropriate endpoint than overall survival to assess the impact of chronic GVHD on survival in such patients.…”

Thrombopoietin concentrations in peripheral blood correlated with platelet numbers in two patients with thrombocytopenia by chronic graft‐versus‐host disease

“…Thrombocytopenia is well known to be one of the clinical manifestations, as well as a prognostic factor, of cGVHD [1][2][3]. However, its causative mechanism has not been clarified.…”