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Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy S Giralt, E Estey, M Albitar, K van Besien, G Rondon, P Anderlini, S O'Brien, I Khouri, J Gajewski, R Mehra, D Claxton, B Andersson, M Beran, D Przepiorka, C Koller, S Kornblau, M Korbling, M Keating, H Kantarjian and R Champlin Department of Hematology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA. The immune-mediated graft-versus-leukemia effect is important to prevent relapse after allogeneic progenitor cell transplantation. This process requires engraftment of donor immuno-competent cells. The objective of this study was to assess the feasibility of achieving engraftment of allogeneic peripheral blood or bone marrow progenitor cell after purine analog containing nonmyeloablative chemotherapy. Patients with advanced leukemia or myelodysplastic syndromes (MDS) who were not candidates for a conventional myeloablative therapy because of older age or organ dysfunction were eligible. All patients had an HLA- identical or one-antigen-mismatched related donor. Fifteen patients were treated (13 with acute myeloid leukemia and 2 with MDS). The median age was 59 years (range, 27 to 71 years). Twelve patients were either refractory to therapy or beyond first relapse. Eight patients received fludarabine at 30 mg/m2/d for 4 days with idarubicin at 12 mg/m2/d for 3 days and ara-c at 2 g/m2/d for 4 days (n = 7) or melphalan at 140 mg/m2/d (n = 1). Seven patients received 2-chloro- deoxyadenosine at 12 mg/m2/d for 5 days and ara-C 1 at g/m2/d for 5 days. Thirteen patients received allogeneic peripheral blood stem cells and 1 received bone marrow after chemotherapy. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methyl- prednisolone. Treatment was generally well tolerated, with only 1 death from multiorgan failure before receiving stem cells. Thirteen patients achieved a neutrophil count of greater than 0.5 x 10(9)/L a median of 10 days postinfusion (range, 8 to 17 days). Ten patients achieved platelet counts of 20 x 10(9)/L a median of 13 days after progenitor cell infusion (range, 7 to 78 days). Eight patients achieved complete remissions (bone marrow blasts were < 5% with neutrophil recovery and platelet transfusion independence) that lasted a median of 60 days posttransplantation (range, 34 to 170+ days). Acute GVHD grade > or = 2 occurred in 3 patients. Chimerism analysis of bone marrow cells in 6 of 8 patients achieving remission showed > or = 90% donor cells between 14 and 30 days postinfusion, and 3 of 4 patients remaining in remission between 60 and 90 days continued to have > or = 80% donor cells. We conclude that purine analog-containing nonmyeloablative regimens allow engraftment of HLA-compatible hematopoietic progenitor cells. This approach permits us to explore the graft-versus-leukemia effect without the toxicity of myeloablative therapy and warrants further study in patients with leukemia who are ineligible for conventional transplantation with myeloablative regimens either because of age or concurrent medical conditions. Volume 89, Issue 12, pp. 4531-4536, 06/15/1997 Copyright © 1997 by The American Society of Hematology CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Ishiyama, A. Takami, S. Suzuki, H. Konaka, M. Namiki, A. Ooi, and S. 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Balduini Hematopoietic Stem-Cell Transplantation for the Bernard-Soulier Syndrome Ann Intern Med, January 7, 2003; 138(1): 79 - 79. [Full Text] [PDF] G. Mufti, A. F. List, S. D. Gore, and A. Y.L. Ho Myelodysplastic Syndrome Hematology, January 1, 2003; 2003(1): 176 - 199. [Abstract] [Full Text] [PDF] R. F. Storb, G. Lucarelli, P. A. McSweeney, and R. W. Childs Hematopoietic Cell Transplantation for Benign Hematological Disorders and Solid Tumors Hematology, January 1, 2003; 2003(1): 372 - 397. [Abstract] [Full Text] [PDF] S. P. Robinson, A. H. Goldstone, S. Mackinnon, A. Carella, N. Russell, C. R. de Elvira, G. Taghipour, and N. Schmitz Chemoresistant or aggressive lymphoma predicts for a poor outcome following reduced-intensity allogeneic progenitor cell transplantation: an analysis from the Lymphoma Working Party of the European Group for Blood and Bone Marrow Transplantation Blood, December 15, 2002; 100(13): 4310 - 4316. [Abstract] [Full Text] [PDF] N. Kroger, H. G. Sayer, R. Schwerdtfeger, M. Kiehl, A. Nagler, H. Renges, T. Zabelina, B. Fehse, F. Ayuk, G. Wittkowsky, et al. Unrelated stem cell transplantation in multiple myeloma after a reduced-intensity conditioning with pretransplantation antithymocyte globulin is highly effective with low transplantation-related mortality Blood, December 1, 2002; 100(12): 3919 - 3924. [Abstract] [Full Text] [PDF] J. A. Perez-Simon, P. D. Kottaridis, R. Martino, C. Craddock, D. Caballero, R. Chopra, J. Garcia-Conde, D. W. Milligan, S. Schey, A. Urbano-Ispizua, et al. Nonmyeloablative transplantation with or without alemtuzumab: comparison between 2 prospective studies in patients with lymphoproliferative disorders Blood, October 16, 2002; 100(9): 3121 - 3127. [Abstract] [Full Text] [PDF] R. Martino, M. D. Caballero, J. A. Perez Simon, C. Canals, C. Solano, A. Urbano-Ispizua, J. Bargay, A. Leon, J. Sarra, G. F. Sanz, et al. Evidence for a graft-versus-leukemia effect after allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning in acute myelogenous leukemia and myelodysplastic syndromes Blood, August 28, 2002; 100(6): 2243 - 2245. [Abstract] [Full Text] [PDF] A. D. Billiau, S. Fevery, O. Rutgeerts, W. Landuyt, and M. Waer Crucial role of timing of donor lymphocyte infusion in generating dissociated graft-versus-host and graft-versus-leukemia responses in mice receiving allogeneic bone marrow transplants Blood, August 13, 2002; 100(5): 1894 - 1902. [Abstract] [Full Text] [PDF] N. Kroger, R. Schwerdtfeger, M. Kiehl, H. G. Sayer, H. Renges, T. Zabelina, B. Fehse, F. Togel, G. Wittkowsky, R. Kuse, et al. Autologous stem cell transplantation followed by a dose-reduced allograft induces high complete remission rate in multiple myeloma Blood, July 18, 2002; 100(3): 755 - 760. [Abstract] [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] D. Forman, R. M. Welsh, T. G. Markees, B. A. Woda, J. P. Mordes, A. A. Rossini, and D. L. Greiner Viral Abrogation of Stem Cell Transplantation Tolerance Causes Graft Rejection and Host Death by Different Mechanisms J. Immunol., June 15, 2002; 168(12): 6047 - 6056. [Abstract] [Full Text] [PDF] S. Chakrabarti, S. Mackinnon, R. Chopra, P. D. Kottaridis, K. Peggs, P. O'Gorman, R. Chakraverty, T. Marshall, H. Osman, P. Mahendra, et al. High incidence of cytomegalovirus infection after nonmyeloablative stem cell transplantation: potential role of Campath-1H in delaying immune reconstitution Blood, May 29, 2002; 99(12): 4357 - 4363. [Abstract] [Full Text] [PDF] M. Alizadeh, M. Bernard, B. Danic, C. Dauriac, B. 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Boeckh, R. A. Carter, B. M. Sandmaier, M. B. Maris, D. G. Maloney, T. Chauncey, P. A. McSweeney, M.-T. Little, L. Corey, et al. Incidence and outcome of cytomegalovirus infections following nonmyeloablative compared with myeloablative allogeneic stem cell transplantation, a matched control study Blood, March 15, 2002; 99(6): 1978 - 1985. [Abstract] [Full Text] [PDF] S. M. Devine, R. Hoffman, A. Verma, R. Shah, B. A. Bradlow, W. Stock, V. Maynard, E. Jessop, D. Peace, M. Huml, et al. Allogeneic blood cell transplantation following reduced-intensity conditioning is effective therapy for older patients with myelofibrosis with myeloid metaplasia Blood, March 15, 2002; 99(6): 2255 - 2258. [Abstract] [Full Text] [PDF] M. Korbling, R. L. Katz, A. Khanna, A. C. Ruifrok, G. Rondon, M. Albitar, R. E. Champlin, and Z. Estrov Hepatocytes and Epithelial Cells of Donor Origin in Recipients of Peripheral-Blood Stem Cells N. Engl. J. Med., March 7, 2002; 346(10): 738 - 746. 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Reduced-intensity conditioning followed by allografting of hematopoietic cells can produce clinical and molecular remissions in patients with poor-risk hematologic malignancies Blood, January 1, 2002; 99(1): 75 - 82. [Abstract] [Full Text] [PDF] F. Weissinger, B. M. Sandmaier, D. G. Maloney, W. I. Bensinger, T. Gooley, and R. Storb Decreased transfusion requirements for patients receiving nonmyeloablative compared with conventional peripheral blood stem cell transplants from HLA-identical siblings Blood, December 15, 2001; 98(13): 3584 - 3588. [Abstract] [Full Text] [PDF] L. Luznik, S. Jalla, L. W. Engstrom, R. Iannone, and E. J. Fuchs Durable engraftment of major histocompatibility complex-incompatible cells after nonmyeloablative conditioning with fludarabine, low-dose total body irradiation, and posttransplantation cyclophosphamide Blood, December 1, 2001; 98(12): 3456 - 3464. [Abstract] [Full Text] [PDF] F. Lan, D. Zeng, M. Higuchi, P. Huie, J. P. Higgins, and S. Strober Predominance of NK1.1+TCR{alpha}{beta}+ or DX5+TCR{alpha}{beta}+ T Cells in Mice Conditioned with Fractionated Lymphoid Irradiation Protects Against Graft-Versus-Host Disease: "Natural Suppressor" Cells J. Immunol., August 15, 2001; 167(4): 2087 - 2096. [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] X.-F. Yang, C. J. Wu, S. McLaughlin, A. Chillemi, K. S. Wang, C. Canning, E. P. Alyea, P. Kantoff, R. J. Soiffer, G. Dranoff, et al. CML66, a broadly immunogenic tumor antigen, elicits a humoral immune response associated with remission of chronic myelogenous leukemia PNAS, June 19, 2001; 98(13): 7492 - 7497. [Abstract] [Full Text] [PDF] K Khawaja, A R Gennery, T J Flood, M Abinun, and A J Cant Bone marrow transplantation for CD40 ligand deficiency: a single centre experience Arch. Dis. Child., June 1, 2001; 84(6): 508 - 511. [Abstract] [Full Text] P. A. McSweeney, D. Niederwieser, J. A. Shizuru, B. M. Sandmaier, A. J. Molina, D. G. Maloney, T. R. Chauncey, T. A. Gooley, U. Hegenbart, R. A. Nash, et al. Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects Blood, June 1, 2001; 97(11): 3390 - 3400. [Abstract] [Full Text] [PDF] F. Lan, D. Zeng, P. Huie, J. P. Higgins, and S. Strober Allogeneic bone marrow cells that facilitate complete chimerism and eliminate tumor cells express both CD8 and T-cell antigen receptor-{alpha}{beta} Blood, June 1, 2001; 97(11): 3458 - 3465. [Abstract] [Full Text] [PDF] A. Badros, B. Barlogie, C. Morris, R. Desikan, S. R. Martin, N. Munshi, M. Zangari, J. Mehta, A. Toor, M. Cottler-Fox, et al. High response rate in refractory and poor-risk multiple myeloma after allotransplantation using a nonmyeloablative conditioning regimen and donor lymphocyte infusions Blood, May 1, 2001; 97(9): 2574 - 2579. [Abstract] [Full Text] [PDF] R. P. Witherspoon, H. J. Deeg, B. Storer, C. Anasetti, R. Storb, and F. R. Appelbaum Hematopoietic Stem-Cell Transplantation for Treatment-Related Leukemia or Myelodysplasia J. Clin. Oncol., April 15, 2001; 19(8): 2134 - 2141. [Abstract] [Full Text] [PDF] W. R. Drobyski, H. C. Morse III, W. H. Burns, J. T. Casper, and G. Sandford Protection from lethal murine graft-versus-host disease without compromise of alloengraftment using transgenic donor T cells expressing a thymidine kinase suicide gene Blood, April 15, 2001; 97(8): 2506 - 2513. [Abstract] [Full Text] [PDF] S. Giralt, P. F. Thall, I. Khouri, X. Wang, I. Braunschweig, C. Ippolitti, D. Claxton, M. Donato, J. Bruton, A. Cohen, et al. Melphalan and purine analog-containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation Blood, February 1, 2001; 97(3): 631 - 637. [Abstract] [Full Text] [PDF] F. R. Appelbaum, J. M. Rowe, J. Radich, and J. E. Dick Acute Myeloid Leukemia Hematology, January 1, 2001; 2001(1): 62 - 86. [Abstract] [Full Text] [PDF]

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