Selective depletion of CD8+ cells for prevention of graft-versus-host disease after bone marrow transplantation. A randomized controlled trial.
We performed a prospective randomized, double-blind study to assess the efficacy of selective depletion of CD8+ bone marrow cells in preventing acute graft-versus-host disease (GVHD) in 38 patients undergoing HLA-identical sibling donor bone marrow transplantation for leukemia. All patients received CsA for GVHD prophylaxis. Nineteen patients received marrow depleted of CD8+ cells by ex vivo treatment with anti-leu2, an anti-CD8 mAb and complement; four patients had moderate (grade 1 or 2 acute GVHD) and the only patient who experienced grade 3 manifestations was a technical failure. The control group consisted of 19 patients who received unmodified bone marrow; one patient had grade 1, 4 patients had grade 2, and 10 had grade 3 or 4 acute GVHD. The actuarial incidence of grade > or = 2 acute GVHD was 20 +/- 20% in the CD8-depleted group compared with 80 +/- 18% in the controls (P = 0.004). Death in 5 of the control patients and the single patient in whom CD8 depletion was a technical failure was related to acute GVHD. Graft failure occurred in 2 patients in the CD8-depleted group and in none of the controls. Leukemic relapse occurred in 2 patients receiving CD8-depleted bone marrow and 2 patients in the control group. Seven patients receiving marrow depleted of CD8+ cells are alive and free of leukemia and 9 patients in the control group are alive, 7 of whom remain leukemia-free (P = 0.88). The 3-year actuarial leukemia-free survival is 37 +/- 22% of the CD8-depleted group and 36 +/- 22% for the control group. These results indicate that selective depletion of CD8+ cells from the bone marrow significantly reduces the incidence and severity of acute GVHD.
Nimer
S D
SD
Department of Medicine, UCLA School of Medicine.
Giorgi
J
J
Gajewski
J L
JL
Ku
N
N
Schiller
G J
GJ
Lee
K
K
Territo
M
M
Ho
W
W
Feig
S
S
Selch
M
M
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000379:methods*; D016516:CD4-CD8 Ratio; D016827:CD8 Antigens / Q000032:analysis*; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000601:surgery*; D015470:Leukemia, Myeloid, Acute / Q000601:surgery*; D008212:Lymphocyte Depletion / Q000379:methods*; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000601:surgery*; D016019:Survival Analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D016827:CD8 Antigens