Immune reconstitution after haematopoietic transplantation with two different doses of pre-graft antithymocyte globulin.
Antithymocyte globulin is widely used before haematopoietic transplantation with HLA-matched unrelated donors or mismatched relatives to prevent rejection and graft-versus-host disease (GVHD). However, optimal dosage is still under debate. Thirty-one consecutive children, mainly with haematological malignancies, were transplanted in a single institution with such donors, selected by HLA-A -B compatibility by serology and DRB1* by DNA typing. Antithymocyte globulin (Thymoglobuline; Sangstat) was infused at days -3, -2, -1. Total dosage varied: 16 patients received a median of 7.5 mg/kg (2.5 to 10.5: low-dose group), and 15 a median of 15.5 mg/kg (14.4 to 19.4: high-dose group). Post-transplant GVHD prophylaxis consisted of cyclosporine, short-course methotrexate and steroids. CD3(+), CD4(+) and CD19(+) cell reconstitution was slower in the high-dose group. Median time to reach 100 CD4(+) cells was 8 months vs 4 months (P = 0.03). Median time to normal CD19(+) cells was 16 months vs 8 months (P = 0.01). CD16(+)CD56(+) and CD8(+) cell reconstitution was similar. Nine patients in the high-dose group and two in the low-dose group experienced life-threatening opportunistic infections (P = 0.009). Although obtained from a limited number of patients, our data suggest that a higher pre-graft dose of antithymocyte globulin may negatively influence immune reconstitution.
D000293:Adolescent; D015703:Antigens, CD / Q000032:analysis; D000961:Antilymphocyte Serum / Q000008:administration & dosage* / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005260:Female; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006648:Histocompatibility / Q000276:immunology; D006801:Humans; D007107:Immune System / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D007223:Infant; D007700:Kinetics; D008297:Male; D009894:Opportunistic Infections; D012189:Retrospective Studies; D014184:Transplantation, Homologous
D015703:Antigens, CD; D000961:Antilymphocyte Serum