The predictive value of helper T lymphocyte precursor frequencies for graft-versus-host disease and graft-versus-leukaemia effects in allogeneic bone marrow transplantation.
Helper T lymphocyte precursor (HTLp) frequencies determined by limiting dilution analysis were studied in the graft-versus-host direction to assess the predictive value for outcome in allogeneic BMT. The HTLp frequencies correlated with the degree of HLA disparity. HTLp frequencies from 28 HLA-identical sibling BMT pairs had a median of 1:557 362 (range 1:9511 to <1:2 500 000). The HTLp frequencies from 20 HLA-matched unrelated and partially HLA-matched related BMT pairs had a median of 1:88 110 (range 1:4139-1:736 123). The HLA-identical sibling BMT pairs were split evenly into high and low HTLp frequency groups above and below 1:500 000. There was a trend towards a higher risk for acute GVHD > or =grade II (P = 0.075) in the high frequency group. There was no difference in TRM. The high HTLp frequency group had a significantly higher risk for chronic GVHD (P = 0.04), a significantly lower risk for relapse (P = 0.01), as well as a significantly better overall survival (P = 0.045) and leukaemia-free survival (P = 0.008). The HLA-matched unrelated and partially HLA-matched related BMT pairs were split evenly into high and low HTLp frequency groups above and below 1:90 000. There was a significantly higher risk for acute GVHD > or = grade II (P = 0.007) in the high HTLp frequency group. There was a trend towards a higher TRM in the high HTLp frequency group (P = 0.05). There were no differences in chronic GVHD, risk of relapse, overall survival and leukaemia-free survival. Analyzing all 48 patients the risk of acute GVHD > or = grade II and TRM was significantly higher (P = 0.012 and 0.021, respectively) with HTLp frequencies >1:100 000 and there was a trend towards a higher risk of relapse (P = 0.058) with low HTLp frequencies <1:400 000. Patients in the intermediate HTLp frequency group 1:100 000-1:400 000 had a trend towards improved survival (P = 0.059). The HTLp frequency seems to detect clinically significant differences in alloreactivity, that can be useful in donor selection and graft engineering.
Russell
C A
CA
Department of Haematology, Rigshospitalet, Copenhagen, Denmark.
Heilmann
C
C
Madsen
H O
HO
Vindeløv
L L
LL
D000293:Adolescent; D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000401:mortality; D018791:CD4 Lymphocyte Count; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000097:blood / Q000175:diagnosis* / Q000401:mortality*; D020544:Graft vs Leukemia Effect; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012720:Severity of Illness Index; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology*; D014184:Transplantation, Homologous / Q000276:immunology / Q000401:mortality; D016896:Treatment Outcome