Influence of anti-thymocyte globulin plasma levels on outcome parameters in stem cell transplanted children
| Autor: | Katharina Wustrau, Ingo Müller, Anne Kruchen, Valentina Vogelsang, Michael Spohn |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Adolescent T-Lymphocytes medicine.medical_treatment Immunology Graft vs Host Disease Hematopoietic stem cell transplantation Gastroenterology Lymphocyte Depletion 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Humans Transplantation Homologous Immunology and Allergy Clinical significance Dosing Child Antilymphocyte Serum Pharmacology medicine.diagnostic_test biology business.industry Hematopoietic Stem Cell Transplantation Infant Anti-thymocyte globulin Treatment Outcome 030104 developmental biology Therapeutic drug monitoring Child Preschool 030220 oncology & carcinogenesis Cohort biology.protein Female Stem cell Antibody business Immunosuppressive Agents |
| Zdroj: | International Immunopharmacology. 83:106371 |
| ISSN: | 1567-5769 |
| DOI: | 10.1016/j.intimp.2020.106371 |
| Popis: | Introduction Allogenic hematopoietic stem cell transplantation is a curative option for malignant and non-malignant pediatric diseases. Serotherapy is often employed to avoid graft-versus-host disease (GvHD) on one hand and graft rejection on the other hand. Therapeutic drug monitoring is increasingly used to allow for more precise dosing especially in pediatric patients due to their specific pharmacological characteristics. Application of T-cell directed antibodies is not routinely monitored, but may benefit from more precise dosing regimens. Methods Two different preparations of rabbit anti-thymocyte globulin (rATG), Thymoglobuline® and ATG-F (Grafalon®), are frequently used to prevent GvHD in pediatric patients by in vivo T-cell depletion. Total rATG levels and active rATG levels were analyzed prospectively in pediatric patients undergoing HSCT. Clinical and laboratory outcome parameters were recorded. Results rATG levels were measured in 32 patients, 22 received thymoglobuline and 10 received ATG-F. The median total peak plasma level was 419.0 µg/ml for ATG-F and 60.4 µg/ml for thymoglobuline. For ATG-F, exposure could be predicted from the calculated dose more precisely than for thymoglobuline. Active peak plasma levels neither of ATG-F, nor of thymoglobuline correlated significantly with the number of lymphocytes prior to serotherapy. There was no significant difference in incidence of aGvHD, cGvHD, rejection, mixed chimerism or viral infections in the two cohorts. However, in our cohort, patients with high thymoglobuline exposure showed a compromised reconstitution of T cells. Conclusions ATG-F and thymoglobuline show different pharmacological and immunological impact in children, whose clinical significance needs to be investigated in larger cohorts. |
| Databáze: | OpenAIRE |
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