Selective T cell depletion of donor allogeneic marrow with anti-CD6 monoclonal antibody: rationale and results.
Acute and chronic graft-versus-host disease (GVHD) are responsible for a significant fraction of the morbidity and mortality of allogeneic bone marrow transplantation. Attempts to reduce the incidence of GVHD by exhaustive T cell depletion of donor marrow have frequently been associated with an increase in graft failure and disease relapse. For the past 10 years, we have evaluated the use of a monoclonal antibody (T12) that selectively targets the CD6 determinant on mature T cells. 171 patients with hematologic malignancies have received donor marrow depleted of mature T cells with anti-CD6 and rabbit complement. Initial engraftment in recipients of HLA-matched marrow has been > 98% with 96% of patients showing stable hematologic reconstitution. The incidence of acute GVHD in this population was only 15%. Chronic GVHD has developed in 5% of patients. Overall, transplant-related mortality was 17%. Examination of peripheral blood lymphocyte reconstitution in the early post-BMT period has been helpful in predicting which patients will ultimately go on to develop GVHD. Treatment of recipients of CD6 depleted marrow with low doses of interleukin-2 post-BMT can expand the number of circulating NK cells and may be associated with a decrease in disease relapse rate.
Soiffer
R J
RJ
Dana-Farber Cancer Institute, Boston, MA 02115.
Ritz
J
J
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D015703:Antigens, CD / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D016026:Bone Marrow Transplantation / Q000473:pathology*; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D015994:Incidence; D007694:Killer Cells, Natural / Q000473:pathology; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D014019:Tissue Donors; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; C062279:CD6 antigen