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Pediatric Transplants

Multivariate analyses of immune reconstitution in children after allo-SCT: risk-estimation based on age-matched leukocyte sub-populations

Abstract

The speed of immune recovery after allo-SCT is of central importance to overcome infectious complications and relapse. To evaluate the immune reconstitution of pediatric patients concerning overall survival, we developed a three-component multivariate model and generated a reference domain of ellipsoidal shape on the basis of normal leukocyte subtype values of 100 healthy children and adolescents. The leukocyte subtypes include absolute nos. of leukocytes, CD14+ monocytes, lymphocytes, CD3+ T cells, CD3+CD4+ helper T cells, CD3+CD8+ cytotoxic T cells, CD3CD56+ natural killer-cells and CD19+ B cells, all of which are correlated, thus, requiring the application of multivariate as opposed to multiple univariate modeling. According to their immune reconstitution, 32 pediatric patients post allo-SCT were classified into low-risk and high-risk groups on the basis of our new model. Therefore, we evaluated if the patients reached the ellipsoid of normal leukocyte sub-population values post SCT. We detected a significantly higher number of long-time survivors among the low-risk group compared with the high-risk group at days 200 (P=0.001) and 300 (P<0.0001). This is superior to our previously published univariate analysis.1 Combined with the clinical observation, a classification into risk groups based on an extended patient cohort may represent a predictor for complications.

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Acknowledgements

This project was supported by ‘Deutsche Forschungsgemeinschaft (DFG, GK-1172)’, ‘Frankfurter Stiftung für Krebskranke Kinder’, ‘Adolf Messer Stiftung’, ‘Paul and Ursula Klein-Stiftung’ and ‘Alfred and Angelika Gutermuth-Stiftung’. We thank Andrea Brinkmann, Stephanie Erben, Carla Fadler, Rabiä el Kalaäoui, Sibylle Wehner, Frauke Röger and Tanja Gardlowski for the excellent technical support and Marco Dreier for data pre-processing.

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Koenig, M., Huenecke, S., Salzmann-Manrique, E. et al. Multivariate analyses of immune reconstitution in children after allo-SCT: risk-estimation based on age-matched leukocyte sub-populations. Bone Marrow Transplant 45, 613–621 (2010). https://doi.org/10.1038/bmt.2009.204

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