Evaluation of abatacept for GVHD prophylaxis in patients with non-malignant diseases after hematopoietic stem cell transplantation

Abstract

Graft-versus-host diseases (GVHD) is one of most significant complication after allogeneic hematopoietic stem cells transplantation (HSCT). T-cell activation is a major stage in the GVHD pathogenesis. T-cells require 2 signals for activation: cognate antigen/MHC binding T-cell receptors and positive costimulatory signals from antigen-presenting cells (APC). The predominant positive costimulatory signal to human CD4 T0-cells comes through the CD28 receptor. This signal can be blocked by fusion proteins (such as CTLA4-Ig). Abatacept is a soluble fusion protein, which links the extracellular domain of human CTLA-4 to the modified Fc portion of human IgG1. We present results of single-center prospective randomized study to evaluate the efficacy of adding abatacept to the GVHD prophylaxis protocol after hemopoietic stem cell transplantation in patients with non-malignant diseases. Study was approved by Ethics Committee and Scientific Council of the Institute (protocol # 9/2013 from 01.10.2013). During 4 years we included 62 patients, 30 of them received abatacept as additional agent. Cumulative incidence of acute GVHD was significantly lower in this group in compare with control group (p = 0,018). When we stratified patients in dependents of graft processing technology, we did not see any advantages of abatacept in patients after transplantation with TCRαβ+/СD19+ graft depletion. However, after HSCT with non-manipulated graft the abatacept showed significant efficacy in aGVHD prophylaxis compared with control group (p = 0,024). Abatacept can be recommended as effective additional agent for GVHD prophylaxis after allogeneic HSCT in patients with non-malignant diseases.