T cell-depleted stem-cell transplantation for adults with hematologic malignancies: Sustained engraftment of HLA-matched related donor grafts without the use of antithymocyte globulin

Adult Allogeneic Bone Marrow Transplant Service, Division of Hematologic-Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Weill Medical College of Cornell University, New York, NY 10065, USA.
Blood (Impact Factor: 10.45). 01/2008; 110(13):4552-9. DOI: 10.1182/blood-2007-06-093880
Source: PubMed


Antithymocyte globulin (ATG) has been used in allogeneic stem-cell transplantation to prevent graft rejection and graft-versus-host disease (GvHD). Its use, however, has been associated with delayed T-cell reconstitution and prolonged susceptibility to opportunistic infections (OIs) especially in patients undergoing T cell-depleted (TCD) transplantation. Recently, a prospective trial was conducted in 52 adult patients (median age, 47 years) with various hematologic malignancies undergoing TCD transplantation from HLA-matched related donors without the use of ATG. The cytoreductive regimen consisted of hyperfractionated total body irradiation (HFTBI), thiotepa, and fludarabine. The preferred source of the graft was peripheral blood stem cells (PBSCs). No additional graft rejection or GvHD prophylaxis was given. All evaluable patients engrafted without any immune-mediated graft rejections. Disease-free survival (DFS) at 3 years was 61% in all patients, and 70% in patients with standard-risk disease. Acute GvHD was limited to grade 2 in 8% and chronic GvHD in 9% of patients. Life-threatening OIs occurred in 3 of 52 patients and was fatal in 1. This study demonstrates durable engraftment with a low incidence of GvHD despite the lack of ATG, as well as the curative potential of this regimen.

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    • "Approaches for the prevention of acute GVHD have utilized donor T cell depletion from the graft prior to infusion since 1980s [1, 53–55], by using physical techniques, density gradient centrifugation, anti-thymocyte globulin [56–59] or monoclonal antibody-based depletion methods, and CD34-cell-positive selection, et al. However, this approach is associated with a higher risk of graft rejection, impaired immune reconstitution, infectious complications, and relapse, and increased risk of primary disease relapse after HCT [60, 61]. Recent single-arm trials have shown 3-year disease-free survival approaching 60% with T cell-depleted peripheral blood stem cell transplantation [62, 63]. "
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