298 Cd3+Cd4+-Lymphocytes as Biomarker Predicting the Outcome of Pediatric Haematopoietic Stem Cell Transplantation Recipients

Abstract

Introduction: Haematopoietic stem cell transplantation (HSCT) may be complicated by severe infectious complications, graft-versus-host disease (GvHD) and relapse/graft failures depending on the lymphocyte immune reconstitution. The goal of this study was to identify biomarkers of immune-reconstitution that may predict outcome in the first three months after transplant.Methods: All children transplanted between 2005-2007 within the UMCU were prospectively included in this study. Immunophenotyping was performed every two weeks after HSCT. In this study we analyzed several parameters of immunereconstitution: AUC, the time and maximum CD3+CD4+, CD3+CD8+ T-cell and CD19+B-cell numbers, the ratio between CD4/CD8 and the relationship between naive and memory cells in relation with survival, acute- and chronic-GvHD. We focused on the age-related differences of the immune system and donor sources. We used a multiplicative intensity model in R.Results: 56 recipients received bone marrow, 12 received a sibling donor, while 26 patients received cord blood derived stem cells. The median age at HSCT was 5.9 years (range 0.11 - 18.1). The log-AUC of CD4+ cells in the first 3 months after HSCT positively predicted survival (P < 0.001, HR 0.68, CI95% 0.55-0.85.Conclusion: The AUC of the number of CD4+ cells, 0-90 days after HSCT, predicted long term outcome after HSCT. A low number of CD4 cells (an AUC of approximately 2000 cells*days) in the first period (< 3mths) after HSCT predicted poor survival. Both in future studies and in clinical practice this biomarker may be used to predict outcome early after transplantation.