Kinetics of active and total thymoglobulin in paediatric stem cell transplantation

• Published in: Bone marrow transplantation (Basingstoke) Vol. 43; no. S1; p. S126
• Main Authors: Jol-van der Zijde, C.M, Jansen-Hoogendijk, A.M, Raaijmakers, S, Egeler, R, Lankester, A.C, Bredius, R.G.M, van Tol, M.J.D
• Format: Journal Article
• Language: English
• Published: Nature Publishing Group 01-03-2009
• Subjects: Graft versus host reaction; Health aspects; Immunoglobulin G; Prevention; Risk factors; Stem cells; T cells; Transplantation; Netherlands
• ISSN: 0268-3369

Introduction: Polyclonal anti-thymocyte globulin (ATG, Imtix) is given prior to paediatric stem cell transplantation (SCT) to prevent rejection and Graft-versus-Host disease (GvHD). Material and methods: In this study the course of the ATG concentration was measured in a cohort of 39 paediatric patients who received their first SCT at the department of Paediatrics of the Leiden University Medical Centre (LUMC) between August '06 and July '08. All patients received 10 mg/kg divided over 4 days, starting between 6 and 4 days prior to SCT. Unique in this study was that serum samples were taken frequently before and after every ATG dose and continued until 3 months post SCT. The active ATG, capable of binding to T-cells, was measured by FACS, whereas the total amount of rabbit IgG was measured by ELISA techniques. Results: It was found that the ATG concentration showed peak and off-peak values between every ATG dose. There was a huge variation between the individual patients, the median total ATG concentration that was reached after the final dose was 80 ug/ml with a range of 52-124 ug/ml, peak values after the subsequent doses were respectively 30-48-62 and 80 ug/ml. the active ATG concentration 12.0 U/ml with a range from 5.1 to 25.4 U/ml. It was found that there is no good correlation between the amount of active ATG and total rabbit-IgG in a patient over the different time points pre and post SCT, therefore FACS is the most reliable method to measure the concentration of active ATG. Although all patients received ATG in a dose of 10 mg/kg a significant difference (P=0.002) was found between the patients with a bodyweight below or above 30 kg, therefore there could be a risk of overdosing in this last group. The clearance of active ATG is much faster than the clearance of total rabbit-IgG with half-lifes of 2-7 days and 5-30 days respectively. In the first days after ATG administration the half-life of the active ATG is even faster. Patients with a low ATG concentration at the moment of transplantation were found to have a higher risk to develop GvHD, some patients with high ATG concentration showed an impaired T-cell recovery. Discussion: It would be ideal to develop a pharmacodynamical model for the dosing of ATG in individual patients, but further research with more patients is needed to make that possible.