Influence of T-cell depletion on chronic graft-versus-host disease: results of a multicenter randomized trial in unrelated marrow donor transplantation

Abstract

Donor-derived T cells have been proposed to play a role in pathogenesis of chronic graft-versus-host disease (cGVHD). The impact of ex vivo T-cell depletion (TCD) on cGVHD was analyzed in a randomized multicenter trial involving unrelated donor marrow transplants. A total of 404 patients diagnosed with hematologic malignancies received a total body irradiation-based myeloablative conditioning regimen. GVHD prophylaxis included TCD plus cyclosporine (CSA) or unmodified grafts with CSA plus methotrexate (M/C). Median recipient age was 31.2 years (range, 0.5-55.6 years); median follow-up time since randomization was 4.2 years. The mean number of T cells infused was 1 log lower on the TCD arm. The incidence of cGVHD at 2 years was similar between the TCD and M/C arms, 29% versus 34% (P = .27), respectively. Survival at 3 years from diagnosis of cGVHD was also similar, (TCD 51% versus M/C 58%; P = .29). The proportion of patients with cGVHD who discontinued immunosuppression at 5 years was not different (TCD 72% versus M/C 63%; P = .27), and incidence of serious infections and leukemia relapse were similar on both treatment arms. In spite of a significant reduction of acute GVHD, TCD did not reduce the incidence of cGVHD or improve survival in patients who developed cGVHD.

Figures

Figure 1.

Cumulative incidence of chronic GVHD and relapse by covariates. (A) Cumulative incidence of chronic GVHD by treatment arm, P = .27. (B) Incidence of chronic GVHD by recipient age, P < .01. (C) Incidence of chronic GVHD by CD34+ dose, P < .01. (D) Cumulative incidence of relapse by treatment arm and chronic GVHD status, P = .87.

Figure 2.

Chronic GVHD clinical manifestations at time of diagnosis.

Figure 3.

Time to being off systemic immunosuppressive therapy and overall survival from transplantation for patients with chronic GVHD. (A) Time to being off systemic immunosuppressive therapy for chronic GVHD, P = .27 at 5 years. (B) Overall survival from time of transplantation for patients with chronic GVHD, P = .30.

Figure 4.

Serious infections in patients surviving 100 days after transplantation. All serious infections were more frequent in patients with cGVHD, *P < .01. Fungal infections were more frequent in patients with cGVHD after TCD, **P = .05.