Association between anti-thymocyte globulin exposure and CD4+ immune reconstitution in paediatric haemopoietic cell transplantation: a multicentre, retrospective pharmacodynamic cohort analysis

摘要: Summary Background Anti-thymocyte globulin (ATG) was introduced into the conditioning regimen in haemopoietic cell transplantation (HCT) to prevent graft-versus-host-disease (GvHD) and graft failure. However, ATG can also cause delayed immune reconstitution of donor T cells. We studied relation between exposure active clinical outcomes children. Methods In this retrospective analysis, all patients (age 0·2–23 years) receiving their first HCT April 1, 2004, 2012, who received (thymoglobulin) two Dutch paediatric programmes were included. The cumulative dose chosen according local protocols given intravenously over 4 days consecutively. measures (maximum concentration, concentration at time HCT, clearance, reach a below lympholytic one arbitrary unit [AU] per mL, total area under curve [AUC], AUC before after HCT) calculated using validated population pharmacokinetic model. main outcome interest (defined as CD4+ cells >0·05 × 10 9 L consecutive measurements within 100 days). Other survival, acute chronic GvHD, used Cox proportional hazard models, logistic regression Fine-Gray competing risk regressions for analyses. Findings 251 chance successful decreased increased (odds ratio 0·991, 95% CI 0·987–0·996; p Interpretation These results stress importance improving efficacy safety by amending dosage timing. Individualised dosing timing aim optimum could result improved HCT. Funding Organization Scientific Research.