Positive selection of CD34+ hematopoietic cells using an immunoaffinity column results in T cell-depletion equivalent to elutriation.
Acute graft-vs.-host disease (GVHD) continues to present a barrier to successful allogeneic marrow transplantation. T cell-depletion may prevent severe GVHD but carries an increased risk of graft rejection and relapse posttransplant. Clinical trials have defined the number of lymphocytes associated with sustained engraftment but low risk of significant GVHD (greater than grade I or II skin only) as < or = 10(5)/kg. We examined T cell-depletion resulting from positive selection of CD34+ hematopoietic cells with a biotinylated monoclonal anti-CD34 antibody and an immunoaffinity column. Eleven patients (six myeloma and five breast cancer) underwent both peripheral blood stem cell (PBSC) collection and marrow harvest prior to autologous transplantation. One PBSC collection and one-third of each marrow underwent column separation. PBSCs were enriched for CD34+ cells from an initial mean of 1.5 to 53.3%, while marrow went from an initial mean of 2.8 to 65.4%. PBSC were depleted of CD3+ cells from an initial mean of 9.6 x 10(9) to 8.6 x 10(6). Marrow CD3+ lymphocyte content was reduced from an initial mean of 5.6 x 10(9) to 8 x 10(5). Since the column permits quantification and salvage of depleted T cells, its use should allow re-addition of T cell-aliquots associated with minimal risk for GVHD and rejection. In addition, since PBSCs were as readily depleted as marrow, allogeneic PBSC transplant may be feasible using this method.
Cottler-Fox
M
M
Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD.
Cipolone
K
K
Yu
M
M
Berenson
R
R
O'Shaughnessy
J
J
Dunbar
C
C
D015703:Antigens, CD / Q000032:analysis*; D018952:Antigens, CD34; D001943:Breast Neoplasms / Q000628:therapy*; D017252:CD3 Complex / Q000032:analysis; D002469:Cell Separation / Q000379:methods*; D002846:Chromatography, Affinity; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D008212:Lymphocyte Depletion / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000628:therapy*; D014182:Transplantation, Autologous
D015703:Antigens, CD; D018952:Antigens, CD34; D017252:CD3 Complex