ORIGINAL ARTICLE Immune recovery in children undergoing allogeneic stem cell transplantation: absolute CD8 þ CD3 þ count reconstitution is associated with survival U Koehl 1 , K Bochennek 1 , SY Zimmermann 1 , T Lehrnbecher 1 , J So¨rensen 1 , R Esser 1 , C Andreas 1 , C Kramm 1 , HP Gru¨ttner 1 , E Falkenberg 2 , A Orth 2 , P Bader 1 , D Schwabe 1 and T Klingebiel 1 1 Paediatric Haematology and Oncology, Johann-Wolfgang-Goethe University, Frankfurt, Germany and 2 Competence Centre of Statistics and Operation Research, University of Applied Sciences, Frankfurt, Germany To evaluate the correlation between kinetics of immune reconstitution and survival, we prospectively evaluated lymphocyte subsets in 32 paediatric patients undergoing allogeneic stem cell transplantation (SCT) for haemato- logical malignancies. Four-colour flow cytometric analysis was performed at short intervals with a median follow-up of 4 years post SCT. A total of 50% of patients reached age-matched 5th percentile of natural killer, cytotoxic T, B and helper T cells 4, 9, 20 and 28 weeks after SCT, respectively, which increased to more than 80% within 1 year after SCT. Transplantation of peripheral blood stem cells (PBSC) seemed to elicit the fastest reconstitution of CD3 þ , CD4 þ CD3 þ , CD8 þ CD3 þ and naı¨ve T cells compared to bone marrow (BM) or CD34-selected PBSC, which did not differ. Most importantly, we observed a significantly higher number of survivors among patients whose CD8 þ CD3 þ absolute counts rose above the 5th percentile of age-matched normal levels during the first year post SCT compared to patients who never reached these levels (19/25 vs 0/7, Po0.001). This was still present in both subgroups, BM- and CD34-selected grafts (P ¼ 0.03, 0.02). These results from a small patient sample underline the importance of particular lymphocyte subsets for the outcome of children undergoing SCT. A larger study with detailed subset analysis is underway. Bone Marrow Transplantation (2007) 39, 269–278. doi:10.1038/sj.bmt.1705584 Keywords: allogeneic transplantation; haematopoietic reconstitution; children Introduction Allogeneic haematopoietic stem cell transplantation (SCT) is a recognized treatment for a subgroup of patients with haematological malignancies. Post SCT, prolonged lym- phocytic immune deficiency is related to infectious morbid- ity 1–3 and an increased risk of relapse, 4 both associated with increased mortality. A number of factors influence the haematopoietic reconstitution after SCT, such as the graft source, 5 the immunosuppressive therapy and the age of the patients. 6 SCT with full peripheral blood stem cell (PBSC) grafts results in an earlier immune reconstitution compared to bone marrow (BM) grafts, whereas CD34-selected (PBSC-CD34 þ ) grafts elicit a haematopoietic recovery similar to BM. 5,7 The differences are attributed to the number of lymphocytes transfused with the grafts. PBSC contain approximately one log more lymphocytes com- pared to BM. 7 Data on the incidence of infections after SCT with regard to the stem cell source are conflicting. Storek et al. 8 reported a higher incidence of infections after BM transplantation (BMT) than after PBSC transplant- ation (PBSCT) in adults, whereas Behringer and co-workers 5 did not observe differences between PBSCT, PBSC-CD34 þ transplantation and BMT in spite of the extremely low amount of T cells infused in the case of PBSC-CD34 þ . Lymphocytic immunodeficiency after adult BMT is pro- longed and more profound than after childhood BMT, 9 associated with a significantly increased risk of life- threatening infections, which in part may be owing to delayed reconstitution of the T-cell receptor repertoire. 10 T cells may be regenerated through two different mechan- isms. One is thymus-dependent and plays a major role in children, leading to an early broad T-cell receptor repertoire. The other, predominant mechanism in case of adults whose thymus is involuted seems to be the expansion of peripheral T cells infused with the graft. 10 As most studies on immune reconstitution after SCT were performed in adults, data in paediatric patients are limited. Moreover, to date, lymphocyte subsets were assessed in monthly or even longer intervals, 3,5–9 which does not allow recognition of transient changes in lymphocyte subsets. Therefore, we measured the Received 8 September 2006; revised 27 November 2006; accepted 18 December 2006 Correspondence: Dr U Koehl, Laboratory of Stem Cell Transplantation and Immunotherapy, Paediatric Haematology and Oncology, Johann- Wolfgang-Goethe University, Theodor Stern Kai 7, 60596 Frankfurt, Germany. E-mail: koehl@em.uni-frankfurt.de Bone Marrow Transplantation (2007) 39, 269–278 & 2007 Nature Publishing Group All rights reserved 0268-3369/07 $30.00 www.nature.com/bmt