Partial CD8+ T-cell depletion of allogeneic peripheral blood stem cell transplantation is insufficient to prevent graft-versus-host disease.
Prior studies suggest that depletion of CD8+ T cells from donor bone marrow or donor lymphocyte infusions can reduce graft-versus-host disease (GVHD) without compromising graft-versus-leukemia. We explored CD8 depletion in patients undergoing matched related donor (MRD, n=25) and unrelated donor (URD, n=16) peripheral blood stem cell transplantation following myeloablative conditioning with cyclophosphamide (60 mg/kg/day i.v. x 2) and total body irradiation (200 cGy x 7 fractions). Ex vivo incubation of mobilized donor peripheral blood cells with anti-CD8 antibody coated high-density microparticles removed 99% of CD8+ cells. The median number of CD8+ cells infused was 3.9 x 10(5) cells/kg (2.2 x 10(5) in MRD, and 8.1 x 10(5) in URD patients). Post transplant immune suppression included tacrolimus in the MRD cohort, and tacrolimus plus mini-methotrexate (5 mg/m2 days +1, 3, 6, 11) in the URD cohort. All 41 patients engrafted. Grade 2-4 acute GVHD incidence was 61% (44% MRD, 88% URD). Chronic GVHD incidence was 50% (48% MRD, 55% URD). Relapse incidence was 4.9%. Estimated event-free and overall survival rates were 65 and 63%, respectively, at 1 year and 56 and 57%, respectively, at 2 years. There was no correlation between CD8+ number and GVHD or survival. A 2-log depletion of CD8+ cells from PBSC is insufficient to prevent GVHD.
Ho
V T
VT
Department of Medical Oncology, Biostatistics, Dana Farber Cancer Institute, Boston, MA 02115, USA. vtho@partners.org
Kim
H T
HT
Li
S
S
Hochberg
E P
EP
Cutler
C
C
Lee
S J
SJ
Fisher
D C
DC
Milford
E
E
Kao
G
G
Daley
H
H
Levin
J
J
Ng
A
A
Mauch
P
P
Alyea
E P
EP
Antin
J H
JH
Soiffer
R J
RJ
D000328:Adult; D018414:CD8-Positive T-Lymphocytes; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control*; D006402:Hematologic Diseases / Q000628:therapy*; D006801:Humans; D008212:Lymphocyte Depletion / Q000379:methods; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation