No Benefit for T-Cell Depletion in Unrelated Donor Transplants

PHILADELPHIA—T-cell depletion had no clear advantage over immunosuppressive drug therapy in patients receiving a matched, unrelated donor bone marrow transplant, John E. Wagner, MD, reported at the 44th Annual Meeting of the American Society of Hematology (ASH abstract 274).

This large multicenter randomized trial produced several interesting results, but the hoped-for reduction in chronic graft-versus-host disease (GVHD) with T-cell depletion was not among them; nor was there an improvement in 3-year disease-free survival, the primary study endpoint.

T-cell depletion was associated with reduced toxicity and reduced risk and severity of acute GVHD, but also with increases in some adverse cancer outcomes. Overall, the treatment comparison was "a wash," Dr. Wagner said at a press conference at the ASH meeting. The results support the conclusion that "matching is still the most critical aspect" of the success of bone marrow transplantation.

The National Heart, Lung, and Blood Institute (NHLBI)-sponsored trial was conducted in 401 patients receiving a transplant for chronic myeloid leukemia (CML) (n = 182), acute myeloid leukemia (AML) (n = 101), acute lymphocytic leukemia (ALL) (n = 88), or other malignancies.

The Hypothesis

"Because the incidence of GVHD is particularly high in recipients of unrelated marrow, it was hypothesized that T-cell depletion would result in decreased risk of nonrelapse mortality by decreasing the toxicities of infection and GVHD," a possibility that was supported by previous experimental and clinical research, said Dr. Wagner, professor of pediatrics, University of Minnesota, and associate director of the Fairview-University Blood and Marrow Transplant Program, Minneapolis.

All patients received a cyclophosphamide/total-body irradiation regimen and post-transplant cyclosporine. Patients were randomized to undergo T-cell depletion or to receive methotrexate on days 1, 3, 6, and 11 post-transplant.

Nearly three fourths of the patients received an HLA-matched graft, while the remaining patients were evenly divided between those with a single HLA A, B, or DRB1 mismatch. At baseline, 43% of patients were cytomegalovirus (CMV) seropositive.

Disease-Free Survival

After a mean of 3 years’ follow-up, disease-free survival was 34% with conventional treatment and 27% with T-cell depletion, a nonsignificant difference. Neither of the treatments had a survival advantage in disease subgroups, Dr. Wagner said, although in patients with CLL, the rate of relapse was higher with T-cell depletion.

The incidence of grade 3 to 4 acute GVHD was lower with T-cell depletion (15% vs 27%, P > .01), but the rate of chronic GVHD at 2 years was similar in both groups at about one fourth. The two treatment groups did not differ in time to engraftment or rate of engraftment, Dr. Wagner reported.

T-cell depletion was associated with a lower incidence and severity of mucositis and hepatic, pulmonary, renal, and central nervous system toxicities than methotrexate/cyclosporine.

Infections were extremely common, with more than 2,600 episodes reported, Dr. Wagner said. The treatments did not differ with regard to most infectious complications; however, T-cell depletion was associated with a higher incidence of CMV infection and with greater severity of these infections.

Cost and Quality of Life

T-cell depletion was associated with a shorter and less costly initial hospitalization, but total duration of hospitalization throughout follow-up did not differ between treatments.

With T-cell depletion, patients "over the first 6-month period after transplantation require less ventilator support, less intensive-care nursing, less hyperalimen-tation, and fewer red cell transfusions," Dr. Wagner said.

Total charges were similar—$235,000 for T-cell depletion and $251,000 for conventional treatment. HLA-mismatched grafts were associated with higher costs than matched grafts, and also with reduced disease-free survival.

The hypothesis that a reduced incidence of acute GVHD would lead to improved quality of life was not borne out, Dr. Wagner said. Functional Assessment of Cancer Therapy (FACT) scores did not differ between the treatment groups at any point during the study. In both groups, quality of life declined at 100 days post-transplant but returned to pretransplant levels at 1 year.