CD52-negative T cells predict acute graft-versus-host disease after an alemtuzumab-based conditioning regimen

Abstract

Allogeneic haematopoietic stem cell transplantation (HSCT) after a reduced-intensity conditioning (RIC) regimen with fludarabine, melphalan and alemtuzmab is an effective therapy for haematological malignancies. Alemtuzumab, a monoclonal antibody against CD52, a glycosylphosphatidylinositol-anchor-bound surface protein on lymphocytes, depletes T cells to prevent graft-versus-host disease (GVHD). Despite this, acute and chronic GVHD (a/cGVHD) remain life-threatening complications after HSCT. The aim of the present study was to identify parameters to predict GVHD. In 69 patients after HSCT, T-cell subsets were functionally analysed. Reconstitution of CD52^neg T cells and CD52^neg regulatory T cells (Tregs) correlated with onset, severity and clinical course of aGVHD. Patients with aGVHD showed significantly lower levels of CD52^pos T cells compared to patients with cGVHD or without GVHD (P < 0·001). Analysis of T-cell reconstitution revealed a percentage of <40% of CD52^pos CD4^pos T cells or CD52^pos Tregs at day +50 as a risk factor for the development of aGVHD. In contrast, CD52^neg Tregs showed significant decreased levels of glycoprotein A repetitions predominant (GARP; P < 0·001), glucocorticoid-induced TNFR-related protein (GITR; P < 0·001), chemokine receptor (CXCR3; P = 0·023), C-C chemokine receptor type 5 (CCR5; P = 0·004), but increased levels of immunoglobulin-like transcript 3 (ILT3; P = 0·001), as well as a reduced suppressive capacity. We conclude that reconstitution of CD52^neg T cells and CD52^neg Tregs is a risk factor for development of aGVHD.

Keywords: GVHD; T cells; T-cell depletion; stem cell transplantation.