CD8+ cell depletion of donor lymphocyte infusions using cd8 monoclonal antibody-coated high-density microparticles (CD8-HDM) after allogeneic hematopoietic stem cell transplantation: a pilot study.
A CD8 murine monoclonal antibody-coated high-density microparticle (HDM) has been developed, which allows for the rapid depletion of CD8+ T cells from apheresis products by gravity sedimentation. We conducted a study to determine the efficacy and safety of CD8 depletion of donor lymphocyte infusions (DLI) to treat relapse after stem cell transplantation using the Eligix CD8-HDM Cell Separation System. Patients were targeted to receive 3 x 10(7) CD4+ T cells/kg. Nine patients were enrolled, three with CML, three myeloma, two CLL, and one NHL. A median of 1 x 10(10) mononuclear cells were obtained by apheresis and processed. The median depletion of CD8+ cells was 99.3% (97.8->99.5%). CD8 depletion was highly specific, with a median recovery of CD4+ cells of 75%. A median of 2.9 x 10(7) CD4+ cells/kg was infused. No infusional toxicity was noted. All CML patients achieved a complete molecular remission. A CLL patient demonstrated a complete response. One patient developed GVHD (grade II acute GVHD and subsequently chronic GVHD). The CD8-HDM Cell Separation System appears to be highly selective and effective in depleting CD8+ T cells from DLI apheresis products, and CD8-depleted DLI is capable of mediating a graft-versus-leukemia effect while minimizing GVHD.
Alyea
E P
EP
Center for Hematologic Oncology, Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. edwin_alyea@DFCI.Harvard.edu
Canning
C
C
Neuberg
D
D
Daley
H
H
Houde
H
H
Giralt
S
S
Champlin
R
R
Atkinson
K
K
Soiffer
R J
RJ
D000328:Adult; D001781:Blood Component Removal / Q000379:methods; D018414:CD8-Positive T-Lymphocytes; D005260:Female; D019337:Hematologic Neoplasms / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D018189:Immunomagnetic Separation; D008212:Lymphocyte Depletion / Q000379:methods*; D017710:Lymphocyte Transfusion / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012008:Recurrence; D016879:Salvage Therapy / Q000379:methods; D014184:Transplantation, Homologous; D016896:Treatment Outcome