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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. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-01-0393v1 106/3/1123    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Solomon, S. R. Articles by Barrett, A. J. Search for Related Content PubMed PubMed Citation Articles by Solomon, S. R. Articles by Barrett, A. J. Related Collections Immunobiology Transplantation Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Mielke, R. Nunes, K. Rezvani, V. S. Fellowes, A. Venne, S. R. Solomon, Y. Fan, E. Gostick, D. A. Price, C. Scotto, et al. A clinical-scale selective allodepletion approach for the treatment of HLA-mismatched and matched donor-recipient pairs using expanded T lymphocytes as antigen-presenting cells and a TH9402-based photodepletion technique Blood, April 15, 2008; 111(8): 4392 - 4402. [Abstract] [Full Text] [PDF] S. Mielke, K. Rezvani, B. N. Savani, R. Nunes, A. S. M. Yong, J. Schindler, R. Kurlander, V. Ghetie, E. J. Read, S. R. Solomon, et al. Reconstitution of FOXP3+ regulatory T cells (Tregs) after CD25-depleted allotransplantion in elderly patients and association with acute graft-versus-host disease Blood, September 1, 2007; 110(5): 1689 - 1697. [Abstract] [Full Text] [PDF] D. Blaise, N. Vey, C. Faucher, and M. Mohty Current status of reduced intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia Haematologica, April 1, 2007; 92(4): 533 - 541. [Abstract] [Full Text] [PDF] T. C. Wehler, M. Nonn, B. Brandt, C. M. Britten, M. Grone, M. Todorova, I. Link, S. A. Khan, R. G. Meyer, C. Huber, et al. Targeting the activation-induced antigen CD137 can selectively deplete alloreactive T cells from antileukemic and antitumor donor T-cell lines Blood, January 1, 2007; 109(1): 365 - 373. [Abstract] [Full Text] [PDF] S. Mielke, K. Rezvani, S. R. Solomon, B. N. Savani, R. Nunes, A. Yong, J. Schindler, E. J. Read, E. S. Vitetta, and A. J. Barrett Selective Depletion of CD25+ Host-Reactive Donor Lymphocytes from Allografts Preserves a CD25- CD4+foxp3+ Fraction of T Cells and Thereby Provides a Source for Efficient Reconstitution of Regulatory T Cells and Additional GVHD Control. Blood (ASH Annual Meeting Abstracts), November 16, 2006; 108(11): 308 - 308. [Abstract] [Full Text] [PDF] J. Barrett Weeding out dangerous alloresponses by graft engineering Blood, September 15, 2006; 108(6): 1786 - 1787. [Full Text] [PDF] P. J. Amrolia, G. Muccioli-Casadei, H. Huls, S. Adams, A. Durett, A. Gee, E. Yvon, H. Weiss, M. Cobbold, H. B. Gaspar, et al. Adoptive immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical stem cell transplantation Blood, September 15, 2006; 108(6): 1797 - 1808. [Abstract] [Full Text] [PDF]

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