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Blood, 1 August 2005, Vol. 106, No. 3, pp. 1123-1129.
Prepublished online as a Blood First Edition Paper on April 7, 2005; DOI 10.1182/blood-2005-01-0393.
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TRANSPLANTATION
Selective depletion of alloreactive donor lymphocytes: a novel method to reduce the severity of graft-versus-host disease in older patients undergoing matched sibling donor stem cell transplantation
Scott R. Solomon,
Stephan Mielke,
Bipin N. Savani,
Aldemar Montero,
Laura Wisch,
Richard Childs,
Nancy Hensel,
John Schindler,
Victor Ghetie,
Susan F. Leitman,
Thao Mai,
Charles S. Carter,
Roger Kurlander,
Elizabeth J. Read,
Ellen S. Vitetta, and
A. John Barrett
From the Stem Cell Allotransplantation Section, Hematology Branch, National Heart, Lung and Blood Institute (NHLBI), the Cell Processing Section, Department of Transfusion Medicine, and the Clinical Center, National Institutes of Health, Bethesda, MD; and the Cancer Immunobiology Center and Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX.
We have selectively depleted host-reactive donor T cells from peripheral blood stem cell (PBSC) transplant allografts ex vivo using an anti-CD25 immunotoxin. We report a clinical trial to decrease graft-versus-host disease (GVHD) in elderly patients receiving selectively depleted PBSC transplants from HLA-identical sibling donors. Sixteen patients (median age, 65 years [range, 51-73 years]), with advanced hematologic malignancies underwent transplantation following reduced-intensity conditioning with fludarabine and either cyclophosphamide (n = 5), melphalan (n = 5), or busulfan (n = 6). Cyclosporine was used as sole GVHD prophylaxis. The allograft contained a median of 4.5 x 106 CD34 cells/kg (range, 3.4-7.3 x 106 CD34 cells/kg) and 1.0 x 108/kg (range, 0.2-1.5 x 108/kg) selectively depleted T cells. Fifteen patients achieved sustained engraftment. The helper T-lymphocyte precursor (HTLp) frequency assay demonstrated successful (mean, 5-fold) depletion of host-reactive donor T cells, with conservation of third-party response in 9 of 11 cases tested. Actuarial rates of acute GVHD were 46% ± 13% for grades II to IV and 12% ± 8% for grades III to IV. These results suggest that allodepletion of donor cells ex vivo is clinically feasible in older patients and may reduce the rate of severe acute GVHD. Further studies with selectively depleted transplants to evaluate graft-versus-leukemia (GVL) and survival are warranted.
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