CAMPATH-1 antibodies in stem-cell transplantation.
BACKGROUND
CAMPATH-1 (CD52) Abs have been used in stem-cell transplants for the prevention of GvHD and graft rejection. These complications can effectively be prevented by depletion of T lymphocytes from both donor and recipient. However, donor lymphocytes might contribute an anti-leukemia effect and lymphocyte depletion may exacerbate problems with immune reconstitution. There is a fine balance between the risks of GvHD and host-versus-graft reactions, relapse and infection.


METHODS
Clinical outcomes for 4264 patients were reported to a central registry and analyzed by univariate and multivariate methods to determine the superior protocols. Various protocols of lymphocyte depletion were tested, using either CAMPATH-1M (IgM) plus complement or CAMPATH-1G (IgG2b) to treat the donor BM ex vivo and CAMPATH-1G in vivo to treat the recipient. The humanized antibody CAMPATH-1H has recently replaced CAMPATH-1G. A meeting of the clinical collaborators was convened to discuss the results and to review the experiences of individual centers.


RESULTS
Interest focused on the use of mobilized PBSC for transplantation and on the use of reduced-intensity conditioning regimens ('mini' or 'non-Correspondence myeloablative' transplants). These approaches are likely to become increasingly important in the future and will allow transplant procedures to be used for relatively older patients. The use of CAMPATH-1G or CAMPATH-1H was associated with a low incidence of GvHD or rejection, though there were some differences that might be related to the longer half-life of the humanized antibody. An unexpected and apparently paradoxical effect of post-transplant CYA was observed - it appeared to reduce the risk of dying from infection after 6 months. Although part of the benefit could be explained by a reduction in GvHD, the effect was still evident when patients with GvHD or graft rejection were excluded from analysis.


CONCLUSIONS
CAMPATH-1H appears to have a useful role in the prevention of graft rejection and GvHD, particularly in patients who are at high risk of these complications. It can equally well be used by admixture with the infused stem cells, or by administration to the patient prior to the transplant. Future studies will seek to understand the mechanism of the CYA effect and to improve the quality of immune reconstitution.
Hale
G
G
Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Cobbold
S
S
Novitzky
N
N
Bunjes
D
D
Willemze
R
R
Prentice
H G
HG
Milligan
D
D
MacKinnon
S
S
Waldmann
H
H
D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use*; D002985:Clinical Protocols; D002986:Clinical Trials as Topic; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects* / Q000379:methods*; D015337:Multicenter Studies as Topic; D015999:Multivariate Analysis; D018579:Patient Selection; D033581:Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000074323:Alemtuzumab