CD52 antibodies for prevention of graft-versus-host disease and graft rejection following transplantation of allogeneic peripheral blood stem cells.
Graft-versus-host disease (GVHD) is a major cause of mortality and morbidity after allogeneic bone marrow transplantation, but can be avoided by removing T lymphocytes from the donor bone marrow. However, T cell depletion increases the risk of graft rejection. In this study, two strategies are used to overcome rejection: (1) use of high doses of stem cells obtained from peripheral blood (PBSC), (2) admixture with a CD52 monoclonal antibody in order to deplete both donor and residual recipient lymphocytes. Two antibodies are compared: CAMPATH-1G (rat IgG2b) and its humanized equivalent CAMPATH-1H (human IgG1). A total of 187 consecutive patients at six centers received PBSC transplants from HLA-matched siblings between 1997 and 1999. A wide spectrum of diseases, both malignant and non-malignant, was included. The recovery of CD34+ cells after antibody treatment was close to 100%. The risk of acute GVHD (grade 2 to 4) was 11% in the CAMPATH-1G group and 4% in the CAMPATH-1H group (P = NS). The risk of chronic GVHD (any grade) was 11% in the CAMPATH-1G group and 24% in the CAMPATH-1H group (P = 0.03) but the risk of extensive chronic GVHD was only 2%. The overall risk of graft failure/rejection was 2%, not significantly different between the two antibodies. Antibody treatment was equally effective at concentrations between 10 microg/ml and 120 microg/ml and it made no significant difference to the outcome whether the patients received post-transplant immunosuppression or not (87% did not). Transplant-related mortality in this heterogenous group of patients (including high-risk and advanced disease) was 22% at 12 months. It is proposed that treatment of peripheral blood stem cells with CAMPATH-1H is a simple and effective method for depleting T cells which may be applicable to both autologous and allogeneic transplants from related or unrelated donors. Special advantages of this approach are the simultaneous depletion of donor B cells (which reduces the risk of EBV-associated lymphoproliferative disease) and the concomitant infusion of CAMPATH-1H to deplete residual recipient T cells and thus prevent graft rejection.
Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
G
G
Hale
P
P
Jacobs
L
L
Wood
W E
WE
Fibbe
R
R
Barge
N
N
Novitzky
C
C
Toit
L
L
Abrahams
V
V
Thomas
D
D
Bunjes
C
C
Duncker
M
M
Wiesneth
D
D
Selleslag
M
M
Hidajat
M
M
Starobinski
P
P
Bird
H
H
Waldmann
D000074323:Alemtuzumab; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006086:Graft vs Host Disease / Q000517:prevention & control*; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006402:Hematologic Diseases / Q000628:therapy*; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D012189:Retrospective Studies; D015996:Survival Rate; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000276:immunology* / Q000401:mortality
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D016179:Granulocyte Colony-Stimulating Factor; D000074323:Alemtuzumab