title: Cytotoxic T lymphocyte precursor frequency analysis in the selection of HLA matched unrelated donors for hematopoietic stem cell transplantation: the correlation of CTLp frequency with HLA class I genotyping and aGVHD development.
abstract: The selection of human leukocyte antigen (HLA) compatible unrelated donors for hematopoietic stem cell transplantation (HSCT) is based on the direct genotyping of HLA class I and class II alleles (HLA-A, -B, -C, -DRB1, -DQB1 loci). The cellular test estimating the frequency of cytotoxic T lymphocyte precursors (CTLp) has been included into the selection procedure of unrelated donors to detect the class I alloreactivity and to predict acute graft versus host disease (aGVHD) occurrence and severity. The relationship between HLA-A, -B, -C high/medium resolution genotyping and CTLp activation was analysed in the cohort of 78 unrelated donor/patient pairs indicated for HSCT. The high frequency of CTLp (> 1:100,000) correlated significantly (p < or = 0.0002) with the incompatibilities in alleles of HLA-A, -B, -C loci. Nevertheless, the results of HLA-A, -B, -C genotyping and CTLp assay are not fully alternative, suggesting that the CTLp test gives its specific information. The high CTLp frequency (CTLpf) in 14/35 pairs fully matched by HLA class-I alleles genotyping could reflect the influence of another factors upon the CTLp activation. On the contrary, the low CTLp frequency values (< or = 1:100,000) found in 8/43 pairs with existing HLA class-I alleles incompatibilities could indicate the immunological permissivity of these particular mismatches. The clinical relevance of the CTLp test for aGVHD prediction has been also analysed. The relationship between CTLp activation in vitro and the incidence and severity of aGVHD was evaluated in 37 patients who underwent allogeneic HSCT. The severe form of aGVHD (grade III-IV) developed in 9 of 18 cases (50%) with the high pretransplant CTLpf value. The patients with the low CTLpf (n = 19) suffered from the severe form of aGVHD in 2 cases (10%) only, the remaining 17 patients from this group were without aGVHD symptoms or developed only the mild form of aGVHD (I-II). The relationship between CTLp results and the incidence and severity of aGVHD was found statistically significant (p < or = 0.01).
authors.affiliation: Institute of Hematology and Blood Transfusion, Prague, Czech Republic. doli@uhkt.cz
authors.forename: L
authors.initials: L
authors.lastname: Dolezalová
authors.forename: M
authors.initials: M
authors.lastname: Vraná
authors.forename: M
authors.initials: M
authors.lastname: Dobrovolná
authors.forename: M
authors.initials: M
authors.lastname: Loudová
authors.forename: V
authors.initials: V
authors.lastname: Cukrová
authors.forename: A
authors.initials: A
authors.lastname: Vítek
authors.forename: J
authors.initials: J
authors.lastname: Sajdová
authors.forename: J
authors.initials: J
authors.lastname: Starý
authors.forename: P
authors.initials: P
authors.lastname: Sedlácek
mesh_terms: D005805:Genes, MHC Class I / Q000235:genetics*; D005838:Genotype; D006086:Graft vs Host Disease / Q000235:genetics* / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007963:Leukocytes, Mononuclear; D011237:Predictive Value of Tests; D016176:T-Lymphocyte Subsets; D013602:T-Lymphocytes, Cytotoxic; D014019:Tissue Donors