PHILADELPHIAT-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
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.
"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.