Selective depletion of CD8+ T lymphocytes for prevention of graft-versus-host disease after allogeneic bone marrow transplantation.
The effects of selectively depleting CD8+ cells from donor bone marrow were assessed in 36 patients receiving transplantation from an HLA-identical sibling as treatment for leukemia. Donor bone marrow underwent ex vivo treatment using anti-Leu-2 monoclonal antibody and complement. Patients received cyclosporine post-transplant for 6 months. Thirty-three patients had initial engraftment. Three failed to have hematologic recovery, and one patient with initial engraftment had late graft failure. The actuarial incidence of grade greater than or equal to 2 acute graft-versus-host disease was 28% +/- 18% and was usually confined to the skin. Of 33 patients with engraftment, 32 were complete chimeras and one had mixed chimerism. The tempo of hematologic and immunologic recovery was comparable with that reported with transplantation of unmodified bone marrow, although CD4+ and CD8+ T cells recovered at comparable rates. The actuarial rate of leukemia relapse was 11% +/- 10%, occurring in three patients with acute leukemia but in none of 13 patients transplanted for chronic myelogenous leukemia. Actuarial survival was 57% +/- 17% at 2 years. These data indicate that after transplantation of marrow depleted of CD8+ cells, engraftment with prompt hematologic and immunologic recovery generally occurs, with a relatively low rate of acute graft-versus-host disease. Graft failure remains a problem despite retention of CD4+ cells within the donor marrow. The lack of leukemia relapse in patients with chronic myelogenous leukemia suggests retention of a graft-versus-leukemia effect, at least for this malignancy.
Champlin
R
R
Division of Hematology/Oncology, UCLA Center for Health Sciences.
Ho
W
W
Gajewski
J
J
Feig
S
S
Burnison
M
M
Holley
G
G
Greenberg
P
P
Lee
K
K
Schmid
I
I
Giorgi
J
J
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D016026:Bone Marrow Transplantation; D016827:CD8 Antigens; D002469:Cell Separation; D002648:Child; D003165:Complement System Proteins; D003524:Cyclosporins / Q000627:therapeutic use; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006801:Humans; D007165:Immunosuppression Therapy; D007938:Leukemia / Q000601:surgery*; D007945:Leukemia, Lymphoid / Q000473:pathology / Q000601:surgery; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology / Q000601:surgery; D015470:Leukemia, Myeloid, Acute / Q000473:pathology / Q000601:surgery; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology; D008297:Male; D006377:T-Lymphocytes, Helper-Inducer / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D003524:Cyclosporins; D003165:Complement System Proteins