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

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.

Figure 1

Kaplan-Meier estimates of the probability of DFS based on status of disease.

Figure 2

Kaplan-Meier estimates of the probability of DFS at 2 years after transplantation for patients younger than 50 years and 50 years or older with standard-risk disease.

Figure 3

Cause-specific analysis of relapse and mortality. (A) Cause-specific probability of relapse, controlling for the competing risks of treatment failure by nonrelapse causes. (B) Cause-specific probability of death, adjusting for the competing risk of relapse.

Figure 4

T-cell recovery. Shown are the 10th, 50th, and 90th percentiles (solid lines, ●) of CD4⁺ and CD4⁺ CD45RA⁺ cells per microliter obtained over 24 to 36 months after transplantation in patients on the current study.