Prognostic significance of recurrent grade 1B rejection in the first year after pediatric cardiac transplantation: a case for reinstatement of the 1B rejection grade

Abstract

The 2005 ISHLT rejection grading system merged grades 1A, 1B, and 2 into a single grade (1R) assuming equivalent prognostic significance. We hypothesized that recurrent 1B ACR is associated with adverse outcomes. Data on all heart transplant recipients at our center from 1990 to 2007 were reviewed. Patients were excluded if they had more than one grade ≥ 3A/2R biopsy in the first six wk or any grade ≥ 3A/2R biopsies during the first year thereafter. Patients with ≥ 2 grade 1B biopsies from six wk to one yr were classified as "recurrent 1B." Outcomes were freedom from late (greater than one yr) ACR (grade ≥ 3A/2R), CAD, retransplantation/death, and a composite end-point. Sixty-two patients (53 non-recurrent 1B, nine recurrent 1B) met inclusion criteria. In univariate analyses, recurrent 1B status was associated with decreased freedom from late ACR (p < 0.001), CAD (p = 0.004), and the composite outcome (p < 0.001). There was no difference in freedom from retransplantation/death (p = 0.48). After controlling for demographic differences between the groups, recurrent 1B status was independently associated with late ACR (HR 5.90; p = 0.002) and the composite outcome (HR 4.52; p = 0.002). These data suggest that further study of the impact of removal of the 1B classification from the ISHLT grading scheme is warranted.

Figure 1

Kaplan-Meier curves showing effect of recurrent 1B group status on late post-transplant outcomes. (a) Freedom from late (>1 year) grade ≥3A/2R acute cellular rejection. (b) Freedom from post-transplant coronary artery disease. (c) Freedom from re-transplantation/death. (d) Freedom from composite end-point (late ≥3A/2R ACR, coronary artery disease, or re-transplantation/death).