SELECTIVE DEPLETION OF CD8(-VERSUS-HOST DISEASE AFTER BONE-MARROW TRANSPLANTATION - A RANDOMIZED CONTROLLED TRIAL() CELLS FOR PREVENTION OFGRAFT)

We performed a prospective randomized, double-blind study to assess th e efficacy of selective depletion of CD8(+) bone marrow cells in preve nting 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 rec eived marrow depleted of CD8(+) cells by ex vivo treatment with anti-l eu2, an anti-CD8 mAb and complement; four patients had moderate (grade 1 or 2 acute GVHD) and the only patient who experienced grade 3 manif estations was a technical failure. The control group consisted of 19 p atients 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 actuar ial incidence of grade greater than or equal to 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 receivi ng 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 S-year actuarial leukemia-free surv ival is 37+/-22% of the CD8-depleted group and 36+/-22% for the contro l group. These results indicate that selective depletion of CD8(+) cel ls from the bone marrow significantly reduces the incidence and severi ty of acute GVHD.