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Prepublished online as a Blood First Edition Paper on May 22, 2003; DOI 10.1182/blood-2003-01-0095. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-01-0095v1 102/6/2004    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 Laport, G. G. Articles by June, C. H. Search for Related Content PubMed PubMed Citation Articles by Laport, G. G. Articles by June, C. H. Related Collections Immunobiology Neoplasia Transplantation Immunotherapy Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 September 2003, Vol. 102, No. 6, pp. 2004-2013 CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Adoptive transfer of costimulated T cells induces lymphocytosis in patients with relapsed/refractory non-Hodgkin lymphoma following CD34+-selected hematopoietic cell transplantation Ginna G. Laport, Bruce L. Levine, Edward A. Stadtmauer, Stephen J. Schuster, Selina M. Luger, Stephan Grupp, Nancy Bunin, Frank J. Strobl, Julio Cotte, Zhaohui Zheng, Brian Gregson, Patricia Rivers, Robert H. Vonderheide, David N. Liebowitz, David L. Porter, and Carl H. June From the Translational Research Program, Abramson Family Cancer Research Institute at The University of Pennsylvania Cancer Center; and the Bone Marrow and Stem Cell Transplant Program, University of Pennsylvania Medical Center, Philadelphia. We explored the feasibility and toxicity of administering escalating doses of anti-CD3/CD28 ex vivo costimulated T cells as a therapeutic adjunct for patients with relapsed, refractory, or chemotherapy-resistant, aggressive non-Hodgkin lymphoma (NHL) following high-dose chemotherapy and CD34+-selected hematopoietic cell transplantation (HCT). Sixteen patients had infusions on day 14 after HCT of autologous T cells that had been stimulated using beads coated with anti-CD3 and anti-CD28 monoclonal antibodies. At baseline, the subjects had severe quantitative and functional T-cell impairments. The culture procedure partially reversed impaired cytokine responsiveness in T cells in vitro and in vivo. Transient dose-dependent infusion toxicities were observed. There was a rapid reconstitution of lymphocytes; however, there were persistent defects in CD4 T cells. Most interestingly, 5 patients had a delayed lymphocytosis between day 30 and day 120 after HCT. Maximal clinical responses included 5 patients with a complete response (CR), 7 patients with a partial response (PR), and 4 patients with stable disease. At a median follow-up of 33 months (range, 26-60 months), 5 patients are alive with stable or relapsed disease and 3 patients remain in CR. In conclusion, this phase 1 trial demonstrates that adoptive transfer of autologous costimulated T cells (1) is feasible in heavily pretreated patients with advanced NHL, (2) is associated with a rapid recovery of lymphocyte counts, (3) reverses cytokine activation deficits in vitro, and (4) is associated with delayed lymphocytosis in a subset of patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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