Donor lymphocyte apheresis for adoptive immunotherapy compared with blood stem cell apheresis.
Donor lymphocyte transfusion has gained considerable interest as adoptive cellular immunotherapy for prevention or treatment of relapse after allogeneic stem cell transplantation. This study was designed to compare the yield of CD3(+), CD3(+)4(+), CD3(+)8(+), CD19(+), CD3(-)56(+)16(+), and CD34(+) cells contained in apheresis products from 61 consecutive non-cytokine treated, human leukocyte antigen (HLA)-matched donors for lymphocyte collection with the corresponding apheresis-derived cell yield from 112 consecutive, HLA-matched donors for blood stem cell collection who received recombinant human granulocyte colony stimulating factor (rhG-CSF, filgrastim) 6 microg/kg every 12 hours until cell collection was completed. Apheresis was started on day 4 or 5 of rhG-CSF treatment. The yield of lymphoid subsets was significantly different in the two sample groups, rhG-CSF treated product yields exceeding untreated product yields by a median of 2.1-fold (range: 1.3-2.6). However, the CD34(+) cell yield in rhG-CSF-treated apheresis products exceeded untreated products by 26-fold. A single untreated apheresis procedure was usually sufficient to collect a target dose of 1 x 10(8)/kg CD3(+) cells. Untreated apheresis products contained a median of 0.2 x 10(6)/kg CD34(+) cells. A potential engraftment dose of > or =0.5 x 10(6) CD34(+) cells per kg of recipient body weight was contained in 16% of 57 untreated apheresis products. One single apheresis performed in a normal, untreated donor provides a sufficient amount of CD3(+) cells for adoptive immunotherapy. Compared with that of an rhG-CSF stimulated apheresis product, the CD34(+) cell count is usually, but not always, below the engraftment dose range. RhG-CSF treatment has little effect on the yield of lymphoid subsets collected by apheresis but is highly selective of the release of CD34(+) cells. This report provides baseline data for studies that will show whether other cytokines such as granulocyte macrophage colony stimulating factor (GM-CSF) and/or Flt-3 Ligand can immunomodulate allotransfusates in vivo to improve the graft-vs.-leukemia (GVL) effect after allogeneic stem cell transplantation, while lowering the incidence and severity of graft-vs.-host disease (GVHD).
Körbling
M
M
The University of Texas M.D. Anderson Cancer Center, Division of Medicine, Department of Blood and Marrow Transplantation, Houston, Texas 77030, USA. mkorblin@mdanderson.org
Giralt
S
S
Khouri
I
I
Mirza
N
N
Donato
M
M
Anderlini
P
P
Fischer
H
H
Andreeff
M
M
McMannis
J
J
Champlin
R
R
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D001772:Blood Cell Count; D001782:Blood Donors; D001835:Body Weight; D005260:Female; D000069585:Filgrastim; D006086:Graft vs Host Disease / Q000209:etiology / Q000517:prevention & control; D020544:Graft vs Leukemia Effect; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006648:Histocompatibility; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects / Q000379:methods*; D007937:Leukapheresis / Q000379:methods*; D007938:Leukemia / Q000097:blood / Q000628:therapy; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets; D017710:Lymphocyte Transfusion / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D014184:Transplantation, Homologous
D015703:Antigens, CD; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim