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

Author:

Jakubowski Ann A.1,Small Trudy N.2,Young James W.1,Kernan Nancy A.2,Castro-Malaspina Hugo1,Hsu Katherine C.1,Perales Miguel-Angel1,Collins Nancy3,Cisek Christine2,Chiu Michelle2,van den Brink Marcel R. M.1,O'Reilly Richard J.2,Papadopoulos Esperanza B.1

Affiliation:

1. Adult Allogeneic Bone Marrow Transplant Service, Division of Hematologic-Oncology, Department of Medicine;

2. Department of Pediatrics; and

3. Department of Clinical Laboratories, Memorial Sloan-Kettering Cancer Center, Weill Medical College of Cornell University, New York, NY

Abstract

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.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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