Cytotoxic T lymphocyte precursor frequency as a predictor of acute graft-versus-host disease in bone marrow transplantation from HLA-identical siblings

The measurement of precursor frequencies of donor anti-recipient cytotoxic T lymphocytes (CTL-p) has been shown to predict the incidence and the sever ity of acute graft-versus-host disease (aGVHD) in unrelated donor bone marr ow transplantation (BR IT). In HLA-identical sibling BMT, where aGVHD is mo st likely caused by minor histocompatibility antigen mismatches, this assay did not appear to be sensitive enough to provide similar predictive inform ation. In this study, the CTL-p frequencies and the incidence and severity of aGVHD in 51 onco-hematological patients transplanted from HLA-identical siblings were compared. Sibling donors were selected on the basis of HLA id entity using serological typing for HLA-A, B, C antigens, whereas HLA-DRB w as tested by molecular analysis. Sibling identity was also confirmed by DNA heteroduplex analyses. Fifteen out of 21 (71%) patients with high precurso r frequency (>1:100 x 10(3)) and 12 out of 30 (40%) with low precursor freq uency (<1:100 x 10(3)) experienced clinically significant (II-IV) aGVHD. A significant correlation (P = 0.04) between CTL-p frequency and severe aGVHD was demonstrated. Moreover there was a positive trend for a high frequency response according to an increasing grade of aGVHD, which was statisticall y significant (P = 0.04). In our experience the CTL-p assay is a helpful pr edictive test for aGVHD in HLA-identical sibling BMT, indicating high risk patients possibly requiring additional prophylaxis.q351uf 3