Immune reconstitution after allogeneic stem cell transplantation: the impact of stem cell source and graft-versus-host disease

Abstract

BACKGROUND AND OBJECTIVES: Bone marrow (BM) and blood stem cell (BSC) allografts differ considerably with respect to their content of progenitor cells and progenitor cell subsets as well as mature lymphocytes. The aim of this prospective, randomized study was to determine whether these differences have an impact on early post-transplant immune recovery. DESIGN AND METHODS: In a prospective randomised study, we found enhanced immune recovery in recipients of BSC allografts compared to in recipients of BM allografts despite transplantation of a lower number of lymphoid progenitors, particularly B-cell progenitors. The large number of mature lymphocytes in BSC allografts is a plausible explanation for this observation. At the progenitor cell level, we found a comparable and very high proportion of progenitor cells involved in lymphopoiesis in both study groups. RESULTS: Patients with extensive chronic GVHD, irrespective of the allograft received, had low immunoglobulin (Ig) levels in serum, low B-cell counts in blood and low numbers of B-cell progenitors in the bone marrow. They also showed high T-cell counts, particularly CD3+CD8+ T-cell counts, which was paralleled by a high number of T-cell progenitors in the bone marrow. In patients with extensive chronic GVHD we found low natural killer (NK)-cell counts which has not been reported previously. INTERPRETATION AND CONCLUSIONS: Early immune recovery is enhanced following BSC allografting compared with BM allografting. This is plausibly explained by the large inoculum of mature lymphocytes in BSC allografts. Following allografting, a higher proportion of the BM progenitor cell compartment is involved in lymphopoiesis than it is in healthy adults. However, B-lymphopoiesis is inhibited in patients with extensive chronic GVHD resulting in impaired B-cell recovery. These patients also seem to show impaired NK-cell recovery.