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Blood, 15 February 2006, Vol. 107, No. 4, pp. 1325-1331. Prepublished online as a Blood First Edition Paper on November 3, 2005; DOI 10.1182/blood-2005-08-3373. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-08-3373v1 107/4/1325    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 Porter, D. L. Articles by June, C. H. Search for Related Content PubMed PubMed Citation Articles by Porter, D. L. Articles by June, C. H. Related Collections Transplantation Immunotherapy Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS A phase 1 trial of donor lymphocyte infusions expanded and activated ex vivo via CD3/CD28 costimulation David L. Porter, Bruce L. Levine, Nancy Bunin, Edward A. Stadtmauer, Selina M. Luger, Steven Goldstein, Alison Loren, Julie Phillips, Sunita Nasta, Alexander Perl, Steven Schuster, Donald Tsai, Ambika Sohal, Elizabeth Veloso, Stephen Emerson, and Carl H. June From the Stem Cell Transplant Program, the Hematology-Oncology Division, and Abramson Cancer Center, University of Pennsylvania, Philadelphia; and the Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute; and Division of Oncology, Children's Hospital of Philadelphia, PA. Donor lymphocyte infusions (DLIs) induce potent graft versus tumor (GVT) effects for relapsed chronic myelogenous leukemia (CML) after allogeneic stem cell transplantation (SCT) but are disappointing for other diseases. Disease resistance can occur if donor T cells are not appropriately activated in vivo. Ex vivo T-cell activation might overcome disease-induced anergy and augment GVT activity. We performed a phase 1 trial of ex vivo–activated DLI (aDLI) for 18 patients with relapse after SCT. Activated donor T cells are produced through costimulation with anti-CD3– and anti-CD28–coated beads. Patients with aggressive malignancies received induction chemotherapy, and all patients received conventional DLI (median, 1.5 x 108 mononuclear cells/kg) followed 12 days later by aDLI. Activated DLI was dose escalated from 1 x 106 to 1 x 108 CD3+ cells per kilogram in 5 levels. Seven patients developed acute graft versus host disease (GVHD) (5 grade I-II, 2 grade III), and 4 developed chronic GVHD. Eight patients achieved complete remission, including 4 of 7 with acute lymphocytic leukemia (ALL), 2 of 4 with acute myelogenous leukemia (AML), 1 with chronic lymphocytic leukemia (CLL), and 1 of 2 with non-Hodgkin lymphoma (NHL). Four complete responders relapsed while 4 remain alive in remission a median 23 months after aDLI. Overall, 10 of 18 remain alive 11 to 53 months after aDLI. Adoptive transfer of costimulated activated allogeneic T cells is feasible, does not result in excessive GVHD, and may contribute to durable remissions in diseases where conventional DLI has been disappointing. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. Vasir, Z. Wu, K. Crawford, J. Rosenblatt, C. Zarwan, A. Bissonnette, D. Kufe, and D. Avigan Fusions of Dendritic Cells with Breast Carcinoma Stimulate the Expansion of Regulatory T Cells while Concomitant Exposure to IL-12, CpG Oligodeoxynucleotides, and Anti-CD3/CD28 Promotes the Expansion of Activated Tumor Reactive Cells J. Immunol., July 1, 2008; 181(1): 808 - 821. [Abstract] [Full Text] [PDF] C. Schmid, M. Labopin, A. Nagler, M. Bornhauser, J. Finke, A. Fassas, L. Volin, G. Gurman, J. Maertens, P. Bordigoni, et al. Donor Lymphocyte Infusion in the Treatment of First Hematological Relapse After Allogeneic Stem-Cell Transplantation in Adults With Acute Myeloid Leukemia: A Retrospective Risk Factors Analysis and Comparison With Other Strategies by the EBMT Acute Leukemia Working Party J. Clin. Oncol., November 1, 2007; 25(31): 4938 - 4945. [Abstract] [Full Text] [PDF] I. G. Schuster, D. H. Busch, E. Eppinger, E. Kremmer, S. Milosevic, C. Hennard, C. Kuttler, J. W. Ellwart, B. Frankenberger, E. Nossner, et al. Allorestricted T cells with specificity for the FMNL1-derived peptide PP2 have potent antitumor activity against hematologic and other malignancies Blood, October 15, 2007; 110(8): 2931 - 2939. [Abstract] [Full Text] [PDF] M. Introna, G. Borleri, E. Conti, M. Franceschetti, A. M. Barbui, R. Broady, E. Dander, G. Gaipa, G. D'Amico, E. Biagi, et al. Repeated infusions of donor-derived cytokine-induced killer cells in patients relapsing after allogeneic stem cell transplantation: a phase I study Haematologica, July 1, 2007; 92(7): 952 - 959. [Abstract] [Full Text] [PDF] S. P. Hilchey, A. De, L. M. Rimsza, R. B. Bankert, and S. H. Bernstein Follicular Lymphoma Intratumoral CD4+CD25+GITR+ Regulatory T Cells Potently Suppress CD3/CD28-Costimulated Autologous and Allogeneic CD8+CD25- and CD4+CD25- T Cells J. Immunol., April 1, 2007; 178(7): 4051 - 4061. [Abstract] [Full Text] [PDF]

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