Infusion of donor leukocytes to induce tolerance in organ allograft recipients.
To further enhance chimerism, 229 primary allograft recipients have received perioperative intravenous infusion of a single dose of 3 to 6 X 10(8) unmodified donor bone marrow (BM) cells/kg body weight. In addition, 42 patients have been accrued in a concurrent protocol involving multiple (up to three) sequential perioperative infusions of 2 x 10(8) BM cells/kg/day from day 0-2 posttransplantation (PTx). Organ recipients (n = 133) for whom BM was not available were monitored as controls. The infusion of BM was safe and except for 50 (18%), all study patients have optimal graft function. Of the control patients, allografts in 30 (23%) have been lost during the course of follow-up. The cumulative risk of acute cellular rejection (ACR) was statistically lower in the study patients compared with that of controls. It is interesting that, 62% of BM-augmented heart recipients were free of ACR (Grade > or = 3A) in the first 6 months PTx compared to controls. The incidence of obliterative bronchiolitis was also statistically lower in study lung recipients (3.8%) compared with the contemporaneously acquired controls (31%). The levels of donor cell chimerism were at least a log higher in the peripheral blood of majority of the study patients compared with that of controls. The incidence of donor-specific hyporeactivity, as determined by one-way mixed leukocyte reaction, was also higher in those BM-augmented liver, kidney, and lung recipients that could be evaluated compared to controls.
Salgar
S K
SK
Thomas E. Starzl Transplantation Institute and the Department of Surgery, University of Pittsburgh Medical Center, Pennsylvania 15213, USA.
Shapiro
R
R
Dodson
F
F
Corry
R
R
McCurry
K
K
Zeevi
A
A
Pham
S
S
Abu-Elmagd
K
K
Reyes
J
J
Jordan
M
M
Keenan
R
R
Griffith
B
B
Sesky
T
T
Ostrowski
L
L
Starzl
T E
TE
Fung
J J
JJ
Rao
A S
AS
D001854:Bone Marrow Cells / Q000276:immunology*; D016026:Bone Marrow Transplantation / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D015994:Incidence; D016030:Kidney Transplantation / Q000276:immunology; D017708:Leukocyte Transfusion; D007962:Leukocytes / Q000276:immunology*; D016031:Liver Transplantation / Q000276:immunology; D016040:Lung Transplantation / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000453:epidemiology / Q000276:immunology; D016377:Organ Transplantation; D018183:Transplantation Chimera / Q000276:immunology; D014184:Transplantation, Homologous / Q000276:immunology