Helper T-lymphocyte precursor frequency predicts the occurrence of graft-versus-host disease and disease relapse after allogeneic bone marrow transplantation from HLA-identical siblings

Abstract

BACKGROUND AND OBJECTIVES: Donor helper T-lymphocytes may be involved in graft-versus-host disease (GVHD) and a graft-versus-leukemia effect after bone marrow transplantation (BMT). We assayed donor helper T-lymphocyte precursor frequencies (HTLP(f)) to see whether they could predict the severity of GVHD and disease relapse after transplantation, thereby facilitating donor selection, pre-transplant counselling and modification of GVHD prophylaxis after BMT. DESIGN AND METHODS: Thirty-six consecutive adult BMT recipients and their HLA-identical sibling donors were recruited. HTLP((f)) was measured as a function of interleukin-2 secretion by alloreactive donor T-cells using a limiting dilution assay. Patients were followed prospectively to assess the severity of GVHD and the status of the primary disease after BMT. RESULTS: Eight donors had HTLP((f)) less than or equal to 10(-6); no recipients of these grafts developed severe GVHD after transplantation. Twenty-eight donors had HTLP(f) greater than 10(-6) and 18 recipients of these grafts developed severe GVHD (> or = grade 2) (chi(2) test, p<0.01). Seven donors had HTLP(f) greater than 10(-5) and no recipient had disease relapse. Twenty-nine donors had HTLP(f) less than or equal to 10(-5), 11 recipients of these grafts developed disease relapse (chi(2) test, p=0.08). INTERPRETATION AND CONCLUSIONS: BMT recipients from HLA-identical sibling donors with low (<10(-6)) and high (>10(-5)) HTLP(f) may have a low risk of acute GVHD and disease relapse after transplantation.