title: Individualized T cell monitored administration of ATG versus OKT3 in steroid-resistant kidney graft rejection.
abstract: Acute steroid-resistant rejection episodes are recommended to be treated with set doses of anti-thymocyte globulin (ATG) or anti-CD3 monoclonal antibody (OKT3). Individualized T cell monitoring has been proposed as a tool for dose finding. A randomized study comparing the efficacy and safety of ATG (n = 27) with OKT3 (n = 28) in the treatment of biopsy verified acute steroid-resistant rejection (ASRR) when both drugs were administered on the basis of daily individualized T cell measurements. A drop to below 50 cells/mm3 CD2+ T cells was considered adequate and used to guide the dose of ATG/OKT3. Demographic, clinical and histopathological severities of rejections were equal in the two groups. During the 10 days of T cell monitoring and antibody treatment, 13 patients were in need of dialysis (ATG = 7/OKT3 = 6). Two grafts did not respond to antibody treatment and were lost due to rejection (ATG = 1/OKT3 = 1). There were 26 biopsy verified re-rejections (ATG = 12/OKT3 = 14) within the first 3 months following antibody treatment. Mean serum creatinine (micromol/L) was similar in the two groups (ATG/OKT3: before rejection 157 +/- 72/151 +/- 88, at start of antibody treatment 308 +/- 125/330 +/- 94, end of antibody treatment 254 +/- 122/246 +/- 144 and at follow-up after a mean of 32 months 166 +/- 55 (n = 24)/164 +/- 57(n = 23)). To keep the T cell count below 50 cells/mm3, average dose ATG given was 354 +/- 151 mg (2.3 administrations, range 1-4) and average OKT3 was 32.5 +/- 6.8 mg in 10 doses. In conclusion, individualized T cell monitored administration of ATG and OKT3 is safe and seems as effective as a standard set dose in treatment of ASRR. Tailoring the dose for each individual patient lowers the cost.
authors.affiliation: Department of Internal Medicine, National Hospital, Oslo, Norway. karsten.midtvedt@rikshospitalet.no
authors.forename: Karsten
authors.initials: K
authors.lastname: Midtvedt
authors.forename: Per
authors.initials: P
authors.lastname: Fauchald
authors.forename: Bjoern
authors.initials: B
authors.lastname: Lien
authors.forename: Anders
authors.initials: A
authors.lastname: Hartmann
authors.forename: Dagfinn
authors.initials: D
authors.lastname: Albrechtsen
authors.forename: Birgitte L
authors.initials: BL
authors.lastname: Bjerkely
authors.forename: Torbjoern
authors.initials: T
authors.lastname: Leivestad
authors.forename: Inge B
authors.initials: IB
authors.lastname: Brekke
mesh_terms: D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D004306:Dose-Response Relationship, Immunologic; D004351:Drug Resistance; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000008:administration & dosage*; D011446:Prospective Studies; D018709:Statistics, Nonparametric; D013256:Steroids / Q000008:administration & dosage; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D000961:Antilymphocyte Serum; D016853:Muromonab-CD3; D013256:Steroids