Pretransplant cytotoxic donor T‐cell activity specific to patient HLA class I antigens correlating with mortality after unrelated BMT

Abstract

Unrelated bone marrow transplantation (BMT) is associated with increased post-transplant complication rates, partly because more transplantation antigens are mismatched than in HLA-identical related BMT. We have shown previously that the cytotoxic T-lymphocyte precursor (CTLp) test performed before transplantation specifically detects HLA class I mismatches demonstrating its usefulness for the identification of new HLA class I alleles. In this study we analysed the clinical relevance of the CTLp test in 41 patients who underwent unrelated BMT between 1990 and 1994. All patient-donor pairs were HLA-A, -B, -DR compatible as defined by AB-serology and oligotyping for DR1-14. The host-reactive CTLp test was performed using previously frozen peripheral blood mononuclear cells (PBMC) as stimulators and PHA blasts as target cells. We found 10 CTLp-positive and 31 CTLp-negative patient-donor pairs. Between the two groups there were no significant differences for age, diagnosis, sex, preconditioning and GvHD prophylaxis. The clinical results for the CTLp positive and the CTLp negative transplants were: severe acute GvHD III-IV 67% and 26% (P = 0.0315), transplant-related mortality 60% and 26% (P = 0.0085), and patient survival at 3.5 years 10% and 54% (P = 0.0006). Seven patient-donor pairs were mismatched for HLA-DR and/or -DQ subtypes. Only one of these seven class II mismatched pairs had a positive CTLp test. In the remaining nine CTLp positive pairs the CTL reactivity was directed against HLA-A, -B or -C antigens, revealing a statistically significant (P < 0.005) correlation between the CTLp frequency and HLA class I matching. In conclusion, the CTLp test helped to select optimally matched bone marrow donors and was particularly useful in association with high resolution oligotyping for DR- and DQ-subtypes for precise matching of both classes of HLA antigens.

Antirecipient helper and cytotoxic T-cell frequencies in bone marrow transplantation

“…IFN-gP f was also associated with aGVHD in patients receiving BMT from HLA-identical siblings, but not in those receiving BMT from MUD. Similar results have been reported by others [19][20][21][22][23][24][25][26] and our group, 27 and the present study demonstrated some interesting findings that might be of clinical importance. First, although HTLP f /CTLP f were associated with aGVHD in general, some patients with high HTLP f /CTLP f did not develop severe aGVHD, whereas others who develop aGVHD had low HTLP f /CTLP f levels.…”

Problems and possible solutions in finding an unrelated bone marrow donor. Results of consecutive searches for 240 Dutch patients

“…[28][29][30] It recogmismatches and for one patient due to advanced disease nizes mismatches for class I, including HLA-C alleles, and status.…”

Immunodominance Hierarchies and Gender Bias in Direct TCD8-Cell Alloreactivity

“…Quantitation of allospecific T-cell precursors, using limiting dilution based assays (LDA; cytotoxic T lymphocyte precursor [CTLp] and helper T lymphocyte precursor) (8,9), have all been used to assess the in vitro allogeneic potential of HLA mismatches (10)(11)(12)(13)(14)(15)(16)(17). However, the correlation between the quantitation of allospecific T-cell precursor frequencies and incidences of graft rejection or GvHD has been disappointing and laboratory-dependent (18)(19)(20)(21)(22)(23)(24)(25).…”