Frequency of donor cytotoxic T cell precursors does not correlate with occurrence of acute graft-versus-host disease in children transplanted using unrelated donors

Bone marrow transplantation (BMT) from unrelated volunteers is frequently associated with both increased incidence and increased severity of acute graft-versus-host disease (GVHD). In the last years, it has been suggested that the analysis of the frequency of cytotoxic T lymphocyte precursors (CTLp) of unrelated HLA-matched donors can be used to detect disparity for HLA class I antigens and as a predictive test for development of severe GVHD. In this report, we summarized our experience regarding 20 pediatric patients affected by various hematological disorders, receiving allogeneic BMT from unrelated donors. HLA class I and II antigens of donor/recipient pairs were determined by means of serological typing, whereas molecular typing of HLA-class II antigens of patients and their potential donors was performed using PCR-SSP and PCR-fingerprinting techniques. CTLp values, estimated using limiting dilution analysis, were high (range, 1:7000-1:40,000) in 9 of 20 patients, while the other 11 children had low or undetectable levels (< 1:100,000) of CTL precursors. CTLp frequency was compared with the incidence and severity of GVHD observed after BMT. Our data demonstrate that the frequency of donor CTLp does not statistically correlate either with the occurrence of clinically significant acute GVHD or with disparity for HLA-class II molecular typing between donor and recipient. In particular, 4 of the 10 evaluable patients with an undetectable CTLp frequency developed grade IV, III, II, and IV acute GVHD, respectively. Although the limited number of subjects studied does not allow us to draw any firm conclusion, our data suggest a certain caution in considering this test suitable for the selection of potential donors.