This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Porter, D. L. Articles by Antin, J. H. Search for Related Content PubMed PubMed Citation Articles by Porter, D. L. Articles by Antin, J. H. Social Bookmarking                            What's this?

Graft-Versus-Tumor Induction With Donor Leukocyte Infusions as Primary Therapy for Patients With Malignancies

From the Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania Medical Center, and Department of Pathology and Laboratory Medicine and Molecular Diagnostic Core Facility, University of Pennsylvania Cancer Center, Philadelphia, PA, and Department of Adult Oncology, Dana-Farber/Partners Cancer Care, and Department of Pathology, Massachusetts General Hospital, Boston, MA.

Address reprint requests to David L. Porter, MD, Division of Hematology-Oncology, 16 Penn Tower, 3400 Spruce St, University of Pennsylvania Medical Center, Philadelphia, PA 19104; email dlporter{at}mail.med.upenn.edu

PURPOSE: Histocompatible allogeneic donor leukocyte infusions (DLIs) were administered as primary cancer therapy in a phase I trial to determine (1) whether mixed chimerism could be detected without a prior allogeneic transplantation, (2) the toxicity of primary DLI, and (3) whether a graft-versus-tumor (GVT) reaction could be observed.

PATIENTS AND METHODS: Eighteen patients were studied. Patients received interferon alfa-2b for a minimum of 4 weeks, followed by DLI (level 1). Patients with no toxicity or engraftment were eligible to receive cytarabine or cyclophosphamide followed by another course of DLI (level 2). Engraftment was determined using polymerase chain reaction amplification of donor and host-specific DNA polymorphisms.

RESULTS: Donor cells were detected in the blood in 14 of 16 assessable patients within 1 hour of DLI. Chimerism detectable 4 weeks after DLI was observed in four patients, and five patients were not assessable. Prior autologous transplantation was associated with late chimerism (P = .0014). Acute graft-versus-host disease (GVHD) occurred in four of 16 assessable patients (grade 1, two patients; grade 2, one patient; grade 4, one patient). One patient with grade 4 acute GVHD developed pancytopenia. Only the four patients treated after prior autologous transplantation developed acute GVHD (P = .0005). Three of four patients with acute GVHD and late chimerism responded to primary DLI, and one patient was not assessable for response.

CONCLUSION: Allogeneic adoptive immunotherapy resulted in sustained chimerism, acute GVHD, and a GVT response in heavily pretreated patients. This indicates that it may be possible to generate a direct GVT response for patients with malignancies without the need for intensive conditioning therapy immediately before DLI. Immunosuppression may be required for sustained donor cell engraftment.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				J. H. Antin Reduced-Intensity Stem Cell Transplantation: "...whereof a little More than a little is by much too much." King Henry IV, part 1, I, 2 Hematology, January 1, 2007; 2007(1): 47 - 54. [Abstract] [Full Text] [PDF]

				S. Kausche, T. Wehler, E. Schnurer, V. Lennerz, W. Brenner, S. Melchior, M. Grone, M. Nonn, S. Strand, R. Meyer, et al. Superior Antitumor In vitro Responses of Allogeneic Matched Sibling Compared with Autologous Patient CD8+ T Cells Cancer Res., December 1, 2006; 66(23): 11447 - 11454. [Abstract] [Full Text] [PDF]

				M. Kami, A. Makimoto, Y. Heike, and Y. Takaue Reduced-intensity Hematopoietic Stem Cell Transplantation (RIST) for Solid Malignancies Jpn. J. Clin. Oncol., December 1, 2004; 34(12): 707 - 716. [Abstract] [Full Text] [PDF]

				P. Bader, H. Kreyenberg, W. Hoelle, G. Dueckers, R. Handgretinger, P. Lang, B. Kremens, D. Dilloo, K.-W. Sykora, M. Schrappe, et al. Increasing Mixed Chimerism Is an Important Prognostic Factor for Unfavorable Outcome in Children With Acute Lymphoblastic Leukemia After Allogeneic Stem-Cell Transplantation: Possible Role For Pre-Emptive Immunotherapy? J. Clin. Oncol., May 1, 2004; 22(9): 1696 - 1705. [Abstract] [Full Text] [PDF]

				M. Y. Mapara and M. Sykes Tolerance and Cancer: Mechanisms of Tumor Evasion and Strategies for Breaking Tolerance J. Clin. Oncol., March 15, 2004; 22(6): 1136 - 1151. [Abstract] [Full Text] [PDF]

				K. S. Peggs, K. Thomson, D. P. Hart, J. Geary, E. C. Morris, K. Yong, A. H. Goldstone, D. C. Linch, and S. Mackinnon Dose-escalated donor lymphocyte infusions following reduced intensity transplantation: toxicity, chimerism, and disease responses Blood, February 15, 2004; 103(4): 1548 - 1556. [Abstract] [Full Text] [PDF]

				N. T. Ueno, Y. C. Cheng, G. Rondon, N. M. Tannir, J. L. Gajewski, D. R. Couriel, C. Hosing, M. J. de Lima, P. Anderlini, I. F. Khouri, et al. Rapid induction of complete donor chimerism by the use of a reduced-intensity conditioning regimen composed of fludarabine and melphalan in allogeneic stem cell transplantation for metastatic solid tumors Blood, November 15, 2003; 102(10): 3829 - 3836. [Abstract] [Full Text] [PDF]

				R. K. Strair, D. Schaar, D. Medina, M. B. Todd, J. Aisner, R. S. DiPaola, J. Manago, B. Knox, A. Jenkinson, R. Senzon, et al. Antineoplastic Effects of Partially HLA-Matched Irradiated Blood Mononuclear Cells in Patients With Renal Cell Carcinoma J. Clin. Oncol., October 15, 2003; 21(20): 3785 - 3791. [Abstract] [Full Text] [PDF]

				V. Montefusco, K. Ballen, and P. Quesenberry Donor lymphocyte infusions as primary therapy for neoplasms Blood, January 1, 2003; 101(1): 373 - 373. [Full Text] [PDF]

				K. K. Ballen, P. S. Becker, R. V. B. Emmons, T. J. Fitzgerald, C. C. Hsieh, Q. Liu, C. Heyes, Y. Clark, W. Levy, J. F. Lambert, et al. Low-dose total body irradiation followed by allogeneic lymphocyte infusion may induce remission in patients with refractory hematologic malignancy Blood, June 28, 2002; 100(2): 442 - 450. [Abstract] [Full Text] [PDF]

				B. I. Rini, T. Zimmerman, W. M. Stadler, T. F. Gajewski, and N. J. Vogelzang Allogeneic Stem-Cell Transplantation of Renal Cell Cancer After Nonmyeloablative Chemotherapy: Feasibility, Engraftment, and Clinical Results J. Clin. Oncol., April 15, 2002; 20(8): 2017 - 2024. [Abstract] [Full Text] [PDF]

				M. Michallet, K. Bilger, F. Garban, M. Attal, A. Huyn, D. Blaise, N. Milpied, P. Moreau, P. Bordigoni, M. Kuentz, et al. Allogeneic Hematopoietic Stem-Cell Transplantation After Nonmyeloablative Preparative Regimens: Impact of Pretransplantation and Posttransplantation Factors on Outcome J. Clin. Oncol., July 15, 2001; 19(14): 3340 - 3349. [Abstract] [Full Text] [PDF]

				N. J. McCarthy and M. R. Bishop Nonmyeloablative Allogeneic Stem Cell Transplantation: Early Promise and Limitations Oncologist, December 1, 2000; 5(6): 487 - 496. [Abstract] [Full Text]

				S. Visonneau, A. Cesano, D. L. Porter, S. L. Luger, L. Schuchter, M. Kamoun, M. H. Torosian, K. Duffy, C. Sickles, E. A. Stadtmauer, et al. Phase I Trial of TALL-104 Cells in Patients with Refractory Metastatic Breast Cancer Clin. Cancer Res., May 1, 2000; 6(5): 1744 - 1754. [Abstract] [Full Text] [PDF]