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Comparisons of alloreactive potential of clinical hematopoietic grafts
W Leung1, M Ramírez, G Mukherjee
1Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-5001, USA. wileung@welchlink.welch.jhu.edu
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.