A study of donor alloreactivity, which may predict acute graft-versus-host disease in HLA identical bone marrow transplantations for early leukaemia

Recent studies performed in Seattle, USA have suggested that pretransplant assignment of high or low donor alloreactivity may predict acute graft-versus-host disease (aGvHD) after allogeneic HLA identical marrow transplantation for acute leukaemia. The effect of such pretransplant assignment was studied in a Scandinavian population of 114 consecutive transplantations for acute and chronic leukaemias in 1st remission (n = 74) or chronic phase (n = 40) performed between 1975 and 1989. The selected cut-off value for discriminating between donors of high and low responding capacity (DRC) was based on distribution plots of results from the pretransplant mixed lymphocyte culture (MLC) and chosen as the median value (80% normalized response). Then 57 donors were assigned with high DRC and 57 donors assigned with low DRC. Kaplan-Meier estimates of the probability of patients to develop Grade II or higher aGvHD in receipt of high or low responder donor transplants were compared by univariant analysis. The patients in first remission or chronic phase transplanted with bone marrow from donors assigned as high or low responders had a 36.1% and 10.6% risk for aGvHD, respectively, a difference found to be significant by log rank test (chi-squared = 10.1, d.f. = 1, P = 0.0015). Subsequent studies of the cellular and humoral requirements for this predictive response of donor cells, by blocking with cytokine specific antibodies, addition of excess of recombinant human cytokines and scanning of lymphocyte subsets during the response, showed that the response against pool cells mostly depended upon IL-2 responding cells with the phenotype CD3+, CD4+, CD8-, CD25+, CD16-. It is concluded that prospective studies of alloreactivity as a risk factor should be performed to confirm the above findings.