T‐cell precursor frequencies and long‐term outcome following unrelated hematopoietic stem cell transplantation

Abstract

Functional assays measuring alloreactivity of donor cells are desired to detect either cryptic epitopes inducing graft-vs.-host disease (GvHD) after human leukocyte antigen (HLA)-identical hematopoietic stem cell transplantation (HSCT) or permissible HLA mismatches. However, their value in predicting GvHD and survival is still limited. We determined the cytotoxic and helper T-cell precursor (CTLp and HTLp) frequencies by limiting dilution analysis (LDA) in 40 unrelated recipient/donor combinations. The median observation period at the time of this writing was 4.44 years (range from 0.1 to 11.28). Better overall survival was observed in patients with rather low host-specific CTLp and HTLp frequencies, whereas a trend toward high CTLp frequencies was seen in patients with higher incidence of acute GvHD, especially in patients mismatched in HLA-C. CTLp and HTLp frequencies did not correlate with the incidence of chronic GvHD and relapse. In conclusion, we detected a trend toward better overall survival of patient/donor pairs with low CTLp and HTLp frequencies, however, recommend to use LDA as an additional tool for identifying the most suitable donor when more than one fully HLA-matched stem cell donor is available.

A Proposed Algorithm Predictive for Cytotoxic T Cell Alloreactivity

“…Quantification of the allogeneic CTL response in vitro was obtained by the CTLp assay (6), because it has been proven to be clinically relevant in predicting allogeneic HSCT outcome (7)(8)(9)(10)(11)(12)(13). These studies focused on the amino acid differences on those parts of MHC class I molecules that are important for TCR contact and/or peptide binding.…”