Frequency of anti-recipient alloreactive helper T-cell precursors in donor blood and graft-versus-host disease after HLA-identical sibling bone-marrow transplantation

A substantial proportion of patients undergoing allogeneic bone-marrow transplantation (BMT) develop moderate-to-severe acute graft-versus-host disease (GVHD). Anti-recipient helper (interleukin-2-producing) T-lymphocyte precursors (HTLp) have an important role in the control and amplification of the alloreactive immune response that initiates GVH D. We used a limiting dilution assay to measure the frequency of HTLp in the blood of marrow donors for 25 patients undergoing genotypically HLA-identical BMT for chronic myeloid leukaemia (n = 20), acute myeloid leukaemia (4), or thalassaemia (1). HTLp frequencies in donor blood ranged from 1 in 18x10 3 to less than 1 in 500x10 3 ; they were significantly higher (p=0·02) in patients with grade II-IV acute GVHD than in those with grade 0-I GVHD. The HTLp assay seems sufficiently sensitive to detect clinically significant minor histocompatibility antigen differences between the donor and recipient. The assay should prove valuable in selecting the best donor/recipient combination and could indicate the need to intensify GVH D prophylaxis when the only available donor has a high HTLp frequency.