Abstract
T-cell reconstitution after allo-SCT initially depends on homeostatic peripheral expansion of donor T cells, the level of which may promote the differentiation of alloreactive and tumor-reactive effectors. IL-7 and IL-15 exert their effect as key homeostatic cytokines. We prospectively investigated plasma levels of IL-7 and IL-15 in a homogeneous group of 40 patients in CR of their hematologic malignancy undergoing myeloablative, fully (10/10) HLA-matched BMT. IL-7 and IL-15 proceeded along similar kinetic courses, peaking at wide ranges (3.8–30.2 and 14.3–66 pg/ml, respectively) on day +14 when all patients were profoundly lymphopenic. Occurrence and grade of subsequent acute GVHD were significantly associated with heightened day +14 IL-7 and IL-15 levels. Association of peak IL-7 level to grade 2–4 acute GVHD was confirmed by Cox multivariate analysis (hazard ratio (HR)=5.38; P=0.022). Malignancy relapse was significantly associated with reduced day +14 levels of IL-15 (Cox multivariate analysis: HR=0.93; P=0.035). Plasma IL-7 and IL-15 levels in the early post transplantation period are therefore biomarkers that can help predict subsequent development of acute GVHD and malignancy relapse.
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Acknowledgements
We thank all the patients who agreed to be enrolled in this study. We also thank the staff of the Service des Maladies du Sang involved in the care of the BMT unit. We acknowledge the dedicated technical assistance of Véronique Lekeux, Virginie Dutriez, Sabaouni Naoual and the staff of the cellular immunology unit of the Service d’Immunologie. This study was supported by a regional PHRC program (Nord pas-de Calais, France).
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Thiant, S., Yakoub-Agha, I., Magro, L. et al. Plasma levels of IL-7 and IL-15 in the first month after myeloablative BMT are predictive biomarkers of both acute GVHD and relapse. Bone Marrow Transplant 45, 1546–1552 (2010). https://doi.org/10.1038/bmt.2010.13
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DOI: https://doi.org/10.1038/bmt.2010.13
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