Abstract

Background aimsTo reduce the risk of graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (alloSCT), T-cell depletion (TCD) of grafts can be performed by the addition of alemtuzumab (ALT) “to the bag” (in vitro) before transplantation. In this prospective study, the authors analyzed the effect of in vitro incubation with 20 mg ALT on the composition of grafts prior to graft infusion. Furthermore, the authors assessed whether graft composition at the moment of infusion was predictive for T-cell reconstitution and development of GVHD early after TCD alloSCT. MethodsSixty granulocyte colony-stimulating factor-mobilized stem cell grafts were obtained from ≥9/10 HLA-matched related and unrelated donors. The composition of the grafts was analyzed by flow cytometry before and after in vitro incubation with ALT. T-cell reconstitution and incidence of severe GVHD were monitored until 12 weeks after transplantation. ResultsIn vitro incubation of grafts with 20 mg ALT resulted in an initial median depletion efficiency of T-cell receptor (TCR) α/β T cells of 96.7% (range, 63.5–99.8%), followed by subsequent depletion in vivo. Graft volumes and absolute leukocyte counts of grafts before the addition of ALT were not predictive for the efficiency of TCR α/β T-cell depletion. CD4pos T cells were depleted more efficiently than CD8pos T cells, and naive and regulatory T cells were depleted more efficiently than memory and effector T cells. This differential depletion of T-cell subsets was in line with their reported differential CD52 expression. In vitro depletion efficiencies and absolute numbers of (naive) TCR α/β T cells in the grafts after ALT incubation were not predictive for T-cell reconstitution or development of GVHD post- alloSCT. ConclusionsThe addition of ALT to the bag is an easy, fast and generally applicable strategy to prevent GVHD in patients receiving alloSCT after myeloablative or non-myeloablative conditioning because of the efficient differential depletion of donor-derived lymphocytes and T cells.

Highlights

  • Allogeneic stem cell transplantation is a potentially curative treatment for patients with a variety of malignant and nonmalignant hematological diseases [1,2]

  • In vitro ALT-based T-cell depletion of stem cell grafts leads to differential depletion of lymphocyte subsets

  • The absolute numbers of memory T cells in the grafts were not predictive for the reconstitution of CD52pos T cells at 3 weeks or 6 weeks after transplantation (Figure 4C). These results indicate that T-cell reconstitution soon after T-cell depletion (TCD) allogeneic stem cell transplantation (alloSCT) cannot be predicted based on the composition of the graft at the moment of infusion into the patient

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Summary

Introduction

Allogeneic stem cell transplantation (alloSCT) is a potentially curative treatment for patients with a variety of malignant and nonmalignant hematological diseases [1,2]. To reduce the risk of graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (alloSCT), T-cell depletion (TCD) of grafts can be performed by the addition of alemtuzumab (ALT) “to the bag” (in vitro) before transplantation. In this prospective study, the authors analyzed the effect of in vitro incubation with 20 mg ALT on the composition of grafts prior to graft infusion. In vitro depletion efficiencies and absolute numbers of (naive) TCR a/b T cells in the grafts after ALT incubation were not predictive for T-

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