Selective depletion of marrow-T cytotoxic lymphocytes (CD8) in the prevention of graft-versus-host disease after allogeneic bone-marrow transplantation.
In vitro depletion of mature pan-T lymphocytes has been widely and successfully used to prevent acute graft-versus-host disease (GVHD) after allogeneic bone-marrow transplantation (BMT). However, this procedure has been associated with a high incidence of graft failure and leukemic relapse. In this pilot study, we evaluated the efficiency of a selective depletion of human marrow T cytotoxic lymphocytes (CD8), a subset essential to induce GVHD in mice. Eleven patients with hematologic malignancies were included (7 HLA-matched BMT, 4 HLA-mismatched BMT). Marrow treatment with 7 anti-CD8 mAbs and rabbit complement resulted in a marked reduction of CD8+ lymphocytes from 15% (median value; range 7%-31%) to 1% (median value; range less than 1%-11%). Acute GVHD was not abolished by this procedure despite postgraft immunosuppression. One patient (HLA-mismatched BMT) rejected his graft and had a full autologous recovery. In conclusion, when compared to the data in the literature, CD8 depletion was shown to be less efficient than pan-T-cell depletion in the prevention of GVHD after allogeneic BMT and was still associated with a major complication associated with this procedure, i.e., graft failure.
Maraninchi
D
D
Marrow Transplant Unit, Institut Paoli-Calmettes, Marseille, France.
Mawas
C
C
Guyotat
D
D
Reiffers
J
J
Vernant
J P
JP
Gratecos
N
N
Hirn
J
J
Novakovitch
G
G
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal; D001853:Bone Marrow / Q000528:radiation effects; D016026:Bone Marrow Transplantation; D002648:Child; D003524:Cyclosporins / Q000008:administration & dosage; D006084:Graft Rejection; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006650:Histocompatibility Testing; D006801:Humans; D007165:Immunosuppression Therapy; D008212:Lymphocyte Depletion; D008727:Methotrexate / Q000008:administration & dosage; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D003524:Cyclosporins; D008727:Methotrexate