Influence of T-cell depletion on chronic graft-versus-host disease: results of a multicenter randomized trial in unrelated marrow donor transplantation.
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.
Pavletic
Steven Z
SZ
University of Nebraska Medical Center, Omaha, USA. pavletis@mail.nih.gov
Carter
Shelly L
SL
Kernan
Nancy A
NA
Henslee-Downey
Jean
J
Mendizabal
Adam M
AM
Papadopoulos
Esperanza
E
Gingrich
Roger
R
Casper
James
J
Yanovich
Saul
S
Weisdorf
Daniel
D
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D006087:Graft vs Host Reaction / Q000276:immunology*; D006801:Humans; D007223:Infant; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D014184:Transplantation, Homologous