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Allogeneic stem cell transplantation has become standard therapy for haematological malignancies through the positive immunologic graft-versus-leukaemia effect. Initial immune recovery relies on peripheral expansion of infused T-cells which switch to a memory-like phenotype. This study prospectively investigated whether changes in subset composition precedes late complications after myeloablative HLA-matched transplantation. Of 80 recipients, 51 experienced neither early infection nor acute graft-versus-host disease (GVHD), of whom 18 were still free of clinical complication throughout 395 – 1564 days of follow-up. Compared with this complication-free subgroup, patients who developed chronic GVHD as the only event recovered similar numbers of circulating T-cells with predominance of CD8+T-cells lacking CC-chemokine receptor-7 and CD28 expression. Conversely, poor CD8+T-cell recovery with diminished numbers of CD28negCD8+T-cells (~1/4thof that of relapse-free patients) preceded occurrence of relapse. In multivariate analysis, lower CD28negCD8+T-cell counts by day 60 were associated with greater risk of subsequent relapse (HR 0.33; 95% CI 0.14 - 0.76; P= 0.01). Enumeration of CD28negCD8+T-cells in patients without early clinical complication could assist in predicting risk of relapse and help build an algorithm for accelerating the immune recovery by reducing the immunosuppressive regimen and considering the introduction of prophylactic donor lymphocyte infusions.

Peripheral G-CSF-mobilized blood stem cells (PBSC), use as alternative to marrow stem cells (MSC), is associated with enhanced engraftment and accelerated hematopoietic recovery after allo-SCT. However, despite an increased number of donor T cells infused, the incidence of acute GVHD with PBSC appears to remain identical or less than with MSC. Recent works on the heterogeneity of the human CD4+and CD8+T cells have individualized 4 subsets: namely, naive (CCR7+CD45RA+), central memory (TCM, CCR7+CD45RA−), effector memory (TEM, CCR7−CD45RA−), and CD45RA+effector memory cells (TEMRA, CCR7−CD45RA+). To our knowledge, the T cell subsets proportions in MSC and PBCSP grafts remain unknown. The impact of the infused T cell subsets on patients' outcome is still to be investigated. Between September 2003 and July 2004, 25 consecutive hematopoietic allo-SCT (12 MSC and 13 PBSC) were considered for this study. Multiple combinations of immunophenotyping analysis were used to prospectively examine immune parameters related to graft as well as to early reconstitution. Early post-transplant complications including acute GVHD, relapse and infections were assessed. As expected, T cells subsets, B cells and NK cells numbers were significantly higher in PBSC grafts (versus MSC). However, proportions of CD4+and CD8+T-cell subsets were comparable in the 2 types of graft and similar to normal values observed with peripheral blood of healthy adults. Table below summarize the distribution of T cell subsets within T CD4+and T CD8+in the two types of graft. The incidence of acute GVHD was significantly higher in pts receiving > 5% of CD8+TEMcells among infused CD8+cells (p<0.05) suggesting a detrimental role of this CD8+subset. Pts who developed acute GVHD, compared to those who did not, had a faster expansion of CD4+and CD8+TEMcells (p<0.003), and CD8+TEMRAcells (p<0.05) after transplantation. Conclusion: this report contributes to the establishment of reference values regarding the distribution of T cell subsets within PBSC and MSC graft. Although, the quantity of infused T cell does not seem to influence early complications after allo-SCT, the qualitative composition of graft regarding T cell subsets, appears to be of great importance in acute GVHD occurrence.