Donor helper T-cell frequencies as predictors of acute graft-versus-host disease in bone marrow transplantation between HLA-identical siblings.
BACKGROUND
Despite the current level of sophistication of molecular typing for class I and class II alleles, a significant proportion (20-40%) of recipients of HLA-identical sibling marrow develop severe, acute graft-versus-host disease (GVHD) after bone marrow transplantation. It has been suggested that the frequency of patient-specific helper T lymphocyte precursors (HTLp) detected in the HLA-identical sibling donor correlates with the incidence and severity of acute GVHD after transplantation.


METHODS
This study group consisted of 42 patients who all received bone marrow from HLA-identical sibling donors from January 1990 to December 1996. Using a limiting dilution analysis, donor HTLp frequencies were determined on samples collected before transplantation. The HTLp assay used the cytotoxic T-cell line, CTLL-2, which proliferates in the presence of interleukin-2. The reliability and reproducibility of this assay was established by using cryopreserved batches of CTLL-2 cells of known sensitivity.


RESULTS
The recipient-directed HTLp frequencies detected in the donor before transplantation were correlated with the incidence and severity of acute GVHD experienced by the recipient after transplantation. Statistical analysis revealed an extremely significant correlation between donor precursor frequencies and the development of acute GVHD in the patient after transplantation (P<0.0001).


CONCLUSIONS
This study suggests that together with molecular typing the HTLp frequency should be considered when selecting the most suitable sibling donor for bone marrow transplantation.
Weston
L E
LE
Tissue Typing Department, New South Wales Red Cross Blood Transfusion Service, Sydney, Australia.
Geczy
A F
AF
Farrell
C
C
D000293:Adolescent; D000328:Adult; D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology* / Q000276:immunology; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D006402:Hematologic Diseases / Q000628:therapy; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D016013:Likelihood Functions; D019520:Living Donors; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008875:Middle Aged; D009679:Nuclear Family; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D015234:HLA-A Antigens; D015235:HLA-B Antigens; D006684:HLA-DR Antigens; D007376:Interleukin-2