Effect on cytokine release and graft-versus-host disease of different anti-T cell antibodies during conditioning for unrelated haematopoietic stem cell transplantation.
Three different types of anti-T cell antibody were used in patients undergoing haematopoietic stem cell transplantation (HSCT) with an HLA-A, -B and -DR compatible unrelated donor: ATG-Fresenius (ATG-F) (n = 26), Thymoglobuline (TMG) (n = 61) and OKT-3 (n = 45). The groups were comparable regarding diagnosis, stage, age, conditioning and GVHD prophylaxis, Adverse events were less frequent after ATG-F treatment. Levels of IL-2, IL-6, IFN-gamma, TNF-alpha and GM-CSF were increased after OKT-3 infusion. In multivariate analysis OKT-3 treatment (P = 0.01), G-CSF treatment (P = 0.02) and a cell dose >/=2.7 x 108/kg (P = 0.03) gave a faster engraftment. Acute GVHD grades II-IV occurred in 25% of the ATG-F patients, 12% of the TMG-patients and 43% (P < 0.001 vs TMG) of the OKT-3 patients. OKT-3 was associated with acute GVHD in multivariate analysis. TRM was 26% using TMG as compared to 43% in the OKT-3 group (P = 0.03). Patient survival at 4 years was 63%, 50% and 45% in the ATG-F, TMG and OKT-3-treated patients, respectively (NS). Relapses were 8%, 49% and 34%, respectively (ATG-F vs TMG, P = 0.03). Relapse-free survivals were 61%, 40% and 37% (NS). Among CML patients the probability of relapse was 61% in TMG-treated patients, while no patients relapsed in the other two groups. To conclude, the type of anti-T cell antibody affects GVHD and relapse after HSCT using unrelated donors.
Remberger
M
M
Department of Clinical Immunology, Karolinska Institute, Huddinge Hospital, Huddinge, Sweden.
Svahn
B M
BM
Hentschke
P
P
Löfgren
C
C
Ringdén
O
O
D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000276:immunology / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D008297:Male; D008659:Metabolic Diseases / Q000628:therapy; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D000906:Antibodies; D016207:Cytokines