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Revision of the 1990 working formulation for cardiac allograft rejection: the Sheffield experience

Objective To audit the 1990 International Society for Heart and Lung Transplantation cardiac rejection criteria and to evaluate the impact on classification and clinical outcomes of a modification in which grade 2 is abolished and grades 1A and 1B are amalgamated into a single “grade 1.” Methods 1652 heart biopsies were reviewed over a four year period. The initial 1348 biopsies (group 1), using the original 1990 criteria, were analysed in terms of diagnostic grade and compared with the 304 biopsies analysed with the modified scheme (group 2). Differences in grading with the 1990 scheme were compared between two groups (1.1 and 1.2) reflecting early and late experience with grading. Subsequently all the grade 2 and grade 1B biopsies were rescored in terms of the modified scheme. Clinical results in terms of actuarial patient survival at one year and freedom from 3A rejection were similarly audited. Results The relative ratios of potentially significant rejection (grade 3A, 3B, 4) remained constant over the entire study in groups 1.1, 1.2, and 2. A 50% reduction in grade 2 biopsy reporting was noted comparing early and late parts of group 1. At subsequent review of the group 1 grade 2 biopsies, 97% could be reassigned to grades 0 or 1 in the modified scheme, with the majority of these diagnoses reflecting Quilty effect/biopsy site reactions. Two cases (3%) of the 77 grade 2 biopsies were regraded as grade 3A rejection, with both occurring within three months of transplantation. None of the grade 1B biopsies had high grade cardiac rejection on review, most of these biopsies similarly showing pronounced Quilty effect and biopsy site reactions. Actuarial survival at one year rose from 86% to 90% during the study, with freedom from 3A rejection remaining unchanged at 80%. Conclusions The original working formulation produces consistent grading except at grade 2, which is judged to be a misnomer resulting from Quilty effect and other non-rejection phenomena. While acceptable standardisation can be achieved with the 1990 scheme, the modified scheme has advantages in that it appears to encourage clear discrimination between significant and non-significant cardiac rejection. Overall, elimination of grade 2 did not produce an increase in higher grades of cardiac rejection, and thus the value of this diagnostic grade is questioned.