Comparisons of alloreactive potential of clinical hematopoietic grafts

Abstract

Background. We sought to compare the immunoreactive potential of human cord blood (CB) versus normal adult bone marrow (BM) versus mobilized blood (peripheral blood stem cells; PBSC) from cancer patients. Methods. Forty mice were randomized to receive a range of doses of T cell-replete cell preparations from one of the above three cell sources. Twenty-eight control mice underwent transplantation with T cell-depleted cells. Mice were observed for 60 days for the development of fatal xenogeneic graft-versus-host disease-like syndrome (GVHDLS). Results. For the mice that had received T cell-replete grafts of CB or BM or PBSC, the duration of GVHDLS free survival of the chimeras was inversely proportional to the number of T cells transplanted. After adjustment for the number of T cells transplanted, the relative hazard of developing fatal GVHDLS was 62-fold higher for PBSC and 210-fold higher for BM as compared with CB. Flow cytometric and histologic analyses of selected chimeras that died of GVHDLS showed extensive proliferation of human T cells in multiple organs. In contrast, mice that survived to day 60 were engrafted with human myeloid and B lymphoid cells. Conclusions. The immunoreactive potential, as measured by this in vivo assay, differed among clinical grafts: BM > PBSC > CB.