title: Frequency of anti-recipient alloreactive helper T-cell precursors in donor blood and graft-versus-host disease after HLA-identical sibling bone-marrow transplantation.
abstract: 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 GVHD. 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 18 x 10(3) to less than 1 in 500 x 10(3); they were significantly higher (p = 0.02) in patients with grade II-IV acute GVHD than in those with grade 0-1 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 GVHD prophylaxis when the only available donor has a high HTLp frequency.
authors.affiliation: Department of Haematology, Royal Postgraduate Medical School, London, UK.
authors.forename: A P
authors.initials: AP
authors.lastname: Schwarer
authors.forename: Y Z
authors.initials: YZ
authors.lastname: Jiang
authors.forename: P A
authors.initials: PA
authors.lastname: Brookes
authors.forename: A J
authors.initials: AJ
authors.lastname: Barrett
authors.forename: J R
authors.initials: JR
authors.lastname: Batchelor
authors.forename: J M
authors.initials: JM
authors.lastname: Goldman
authors.forename: R I
authors.initials: RI
authors.lastname: Lechler
mesh_terms: D000293:Adolescent; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D004739:England / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006086:Graft vs Host Disease / Q000145:classification / Q000453:epidemiology / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D015994:Incidence; D007201:Indicator Dilution Techniques / Q000592:standards; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy; D015470:Leukemia, Myeloid, Acute / Q000628:therapy; D008297:Male; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D013789:Thalassemia / Q000628:therapy; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000276:immunology*
chemical_list: D006680:HLA Antigens