Mechanism of graft failure in HLA-matched and HLA-mismatched bone marrow transplant recipients

This report characterizes the mechanism of graft failure in five patients who received allogeneic marrow depleted of T cells in vitro using anti-T12 (CD6) monoclonal antibody and rabbit complement. This group of five patients represents all patients who experienced early graft failure in a larger group of 59 consecutive patients given T12 depleted marrow over a 5-year period. Although all patients received ablative pre-transplant conditioning including total body irradiation (12-14 Gy) graft failure was more frequent in patients without genetically HLA-identical donors (four of 11 patients) than in patients with HLA identical sibling donors (one of 48 patients). In patients without genotypically identical donors, graft failure was observed with variable degrees of genetic disparity including two patients with HLA haplotype-mismatched sibling donors, one patient with a phenotypically HLA-matched parental donor, and one patient with an HLA-matched unrelated donor. In patients with both HLA identical and non-identical donors, results of immunophenotypic analysis demonstrated that early graft failure was associated with peripheral lymphocytosis with T cells expressing CD2, CD3, CD5, CD6, CD8 and Ia antigens. Direct cytotoxicity studies demonstrated specific lysis of donor cells by circulating lymphocytes and further analysis indicated that effector cells were derived from the recipients and not donors. Taken together, these results suggest that these allogeneic grafts did not 'fail', but rather that residual host cytotoxic T cells were responsible for active rejection of donor marrow.(ABSTRACT TRUNCATED AT 250 WORDS)