Lymphocyte growth from cardiac allograft biopsy specimens with no or minimal cellular infiltrates: association with subsequent rejection episode.

Histologic features of endomyocardial biopsy specimens are essential in the monitoring of heart transplant patients. Significant cellular infiltrates accompanied by myocyte damage are diagnostic of transplant rejection, whereas no or minimal infiltrates (grades 0 and 1) suggest absence of rejection. Biopsy specimens were cultured on the basis of the principle that the allograft is infiltrated by activated lymphocytes, which can be expanded in the presence of interleukin-2, a lymphokine that induces proliferation of activated T cells. Although frequency of cell cultures was proportional to histologic rejection grade, 39% of biopsy specimens with grades 0 and 1 cultured during the first month posttransplantation yielded lymphocyte growth. Cell growth was observed in 28% of biopsy specimens with grades 0 and 1 obtained during the first 10 days posttransplantation. In this group (growers) 73% showed clinical rejection after 9.8 +/- 5.0 days. In contrast, 55% of nongrowers were treated for rejection after 19.1 +/- 13.8 days. For biopsy specimens obtained 11 to 20 days posttransplantation, subsequent rejection episodes were observed in 61% of growers, but in only 33% of nongrowers. For biopsy specimens obtained 21 to 30 days posttransplantation the incidence of clinical rejection was 60% versus 14%, respectively. A sequential analysis of biopsy specimens obtained during the first month posttransplantation enabled us to identify 16 persistent nongrowers; only 6 (37%) experienced clinical rejection during the first 3 months posttransplantation. Most of the persistent nongrowers were found among patients on the immunoprophylactic rabbit antithymocyte globulin protocol. These data suggest that in vitro cultures of biopsy specimens with no detectable or minimal cellular infiltration may be useful in identifying patients at risk of developing rejection.