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Blood, Vol. 92 No. 12 (December 15), 1998:
pp. 4581-4590
Improving the Outcome of Bone Marrow Transplantation by Using CD52
Monoclonal Antibodies to Prevent Graft-Versus-Host Disease and Graft
Rejection
Geoff Hale,
Mei-Jie Zhang,
Donald Bunjes,
H. Grant Prentice,
David Spence,
Mary M. Horowitz,
A. John Barrett, and
Herman Waldmann
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. This study
examined the use of CD52 monoclonal antibodies to eliminate T cells
from both donor marrow and recipient to prevent both GVHD and
rejection. Seventy patients receiving HLA-identical sibling transplants
for acute myelogenous leukemia (AML) in first remission were studied.
An IgM (CAMPATH-1M) was used for in vitro depletion of the graft and an
IgG (CAMPATH-1G) for in vivo depletion of the recipient before graft
infusion. No posttransplant immunosuppression was given. Results were
compared with two control groups: (1) 50 patients who received bone
marrow depleted with CAMPATH-1M, but no CAMPATH-1G in vivo; and (2) 459 patients reported to the International Bone Marrow Transplant Registry
(IBMTR) who received nondepleted grafts and conventional GVHD
prophylaxis with cyclosporin A (CyA) and methotrexate (MTX). The
incidence of acute GVHD was 4% in the treatment group compared with
35% in the CyA/MTX group (P < .001). Chronic GVHD was also
exceptionally low in the treatment group (3% v 36%; P < .001). The problem of graft rejection, which had been frequent in
the historic CAMPATH-1M group (31%), was largely overcome in the
treatment group (6%). Thus, transplant-related mortality of the
treatment group (15% at 5 years) was lower than for the CyA/MTX group
(26%; P = .04). There was little difference in the risk of
leukemia relapse between the treatment group (30% at 5 years) and the
CyA/MTX group (29%). Survival of the treatment group at 6 months was
better than the CyA/MTX group (92% v 78%), although at 5 years the difference was not significant (62% v 58%) and
neither was the difference in leukemia-free survival (60% v
52%). We conclude that T-cell depletion is a useful strategy to
prevent GVHD, provided that measures are taken to ensure engraftment. Using CAMPATH-1G to deplete residual host lymphocytes is a simple and
practical method to do this. At least in AML, the beneficial reduction
in GVHD can be achieved without an increased risk of relapse.
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