Faculty Collaboration Database

Improving the outcome of bone marrow transplantation by using CD52 monoclonal antibodies to prevent graft-versus-host disease and graft rejection. Blood 1998 Dec 15;92(12):4581-90

Date

12/09/1998

Pubmed ID

9845524

DOI

10.1182/blood.v92.12.4581

Scopus ID

2-s2.0-0032535279 (requires institutional sign-in at Scopus site)   173 Citations

Abstract

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.

Author List

Hale G, Zhang MJ, Bunjes D, Prentice HG, Spence D, Horowitz MM, Barrett AJ, Waldmann H

Authors

Mary M. Horowitz MD, MS Professor in the Medicine department at Medical College of Wisconsin
Mei-Jie Zhang PhD Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Alemtuzumab
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Antibodies, Neoplasm
Bone Marrow Transplantation
Cyclosporine
Disease-Free Survival
Graft Rejection
Graft vs Host Disease
Humans
Immunosuppressive Agents
Leukemia, Myeloid, Acute
Lymphocyte Depletion
Methotrexate
Multivariate Analysis
Prognosis
Time Factors
Transplantation Conditioning
Treatment Outcome