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Related Collections Neoplasia Transplantation Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 June 2001, Vol. 97, No. 11, pp. 3390-3400 CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects Peter A. McSweeney, Dietger Niederwieser, Judith A. Shizuru, Brenda M. Sandmaier, Arthur J. Molina, David G. Maloney, Thomas R. Chauncey, Theodore A. Gooley, Ute Hegenbart, Richard A. Nash, Jerald Radich, John L. Wagner, Steven Minor, Frederick R. Appelbaum, William I. Bensinger, Eileen Bryant, Mary E. D. Flowers, George E. Georges, F. Carl Grumet, Hans-Peter Kiem, Beverly Torok-Storb, Cong Yu, Karl G. Blume, and Rainer F. Storb From the Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, and Veterans Affairs Medical Center, Seattle, WA; Stanford University, Stanford, CA; and University of Leipzig, Germany. Toxicities have limited the use of allogeneic hematopoietic cell transplantation (HCT) to younger, medically fit patients. In a canine HCT model, a combination of postgrafting mycophenolate mofetil (MMF) and cyclosporine (CSP) allowed stable allogeneic engraftment after minimally toxic conditioning with low-dose (200 cGy) total-body irradiation (TBI). These findings, together with the known antitumor effects of donor leukocyte infusions (DLIs), led to the design of this trial. Forty-five patients (median age 56 years) with hematologic malignancies, HLA-identical sibling donors, and relative contraindications to conventional HCT were treated. Immunosuppression involved TBI of 200 cGy before and CSP/MMF after HCT. DLIs were given after HCT for persistent malignancy, mixed chimerism, or both. Regimen toxicities and myelosuppression were mild, allowing 53% of eligible patients to have entirely outpatient transplantations. Nonfatal graft rejection occurred in 20% of patients. Grades II to III acute graft-versus-host disease (GVHD) occurred in 47% of patients with sustained engraftment. With median follow-up of 417 days, survival was 66.7%, nonrelapse mortality 6.7%, and relapse mortality 26.7%. Fifty-three percent of patients with sustained engraftment were in complete remission, including 8 with molecular remissions. This novel allografting approach, based on the use of postgrafting immunosuppression to control graft rejection and GVHD, has dramatically reduced the acute toxicities of allografting. HCT with the induction of potent graft-versus-tumor effects can be performed in previously ineligible patients, largely in an outpatient setting. Future protocol modifications should reduce rejection and GVHD, thereby facilitating studies of allogeneic immunotherapy for a variety of malignancies. © 2001 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: M. Mielcarek, B. E. Storer, M. Boeckh, P. A. Carpenter, G. B. McDonald, H. J. Deeg, R. A. Nash, M. E. D. Flowers, K. Doney, S. Lee, et al. Initial therapy of acute graft-versus-host disease with low-dose prednisone does not compromise patient outcomes Blood, March 26, 2009; 113(13): 2888 - 2894. [Abstract] [Full Text] [PDF] K. J. Thomson, E. C. Morris, A. Bloor, G. Cook, D. Milligan, A. Parker, F. Clark, L. Yung, D. C. Linch, R. Chakraverty, et al. Favorable Long-Term Survival After Reduced-Intensity Allogeneic Transplantation for Multiple-Relapse Aggressive Non-Hodgkin's Lymphoma J. Clin. Oncol., January 20, 2009; 27(3): 426 - 432. 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Urbano-Ispizua Hematopoetic stem cell transplantation for solid tumors in Europe Ann. Onc., April 1, 2004; 15(4): 653 - 660. [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] T. D. Shanafelt and T. G. Call Current Approach to Diagnosis and Management of Chronic Lymphocytic Leukemia Mayo Clin. Proc., March 1, 2004; 79(3): 388 - 398. [Abstract] [PDF] C. Carvallo, N. Geller, R. Kurlander, R. Srinivasan, O. Mena, T. Igarashi, L. M. Griffith, W. M. Linehan, and R. W. Childs Prior chemotherapy and allograft CD34+ dose impact donor engraftment following nonmyeloablative allogeneic stem cell transplantation in patients with solid tumors Blood, February 15, 2004; 103(4): 1560 - 1563. [Abstract] [Full Text] [PDF] H.-J. Kolb, C. Schmid, A. J. Barrett, and D. J. Schendel Graft-versus-leukemia reactions in allogeneic chimeras Blood, February 1, 2004; 103(3): 767 - 776. [Abstract] [Full Text] [PDF] W. A. Bethge, U. Hegenbart, M. J. Stuart, B. E. Storer, M. B. Maris, M. E. D. Flowers, D. G. Maloney, T. Chauncey, B. Bruno, E. Agura, et al. Adoptive immunotherapy with donor lymphocyte infusions after allogeneic hematopoietic cell transplantation following nonmyeloablative conditioning Blood, February 1, 2004; 103(3): 790 - 795. [Abstract] [Full Text] [PDF] P. Guardiola, G. Socie, X. Li, P. Ribaud, A. Devergie, H. Esperou, P. Richard, R. Traineau, A. Janin, and E. Gluckman Acute graft-versus-host disease in patients with Fanconi anemia or acquired aplastic anemia undergoing bone marrow transplantation from HLA-identical sibling donors: risk factors and influence on outcome Blood, January 1, 2004; 103(1): 73 - 77. [Abstract] [Full Text] [PDF] W. J. Hogan, M. Maris, B. Storer, B. M. Sandmaier, D. G. Maloney, H. G. Schoch, A. E. Woolfrey, H. M. Shulman, R. Storb, and G. B. McDonald Hepatic injury after nonmyeloablative conditioning followed by allogeneic hematopoietic cell transplantation: a study of 193 patients Blood, January 1, 2004; 103(1): 78 - 84. [Abstract] [Full Text] [PDF] S. S. B. Randolph, T. A. Gooley, E. H. Warren, F. R. Appelbaum, and S. R. Riddell Female donors contribute to a selective graft-versus-leukemia effect in male recipients of HLA-matched, related hematopoietic stem cell transplants Blood, January 1, 2004; 103(1): 347 - 352. [Abstract] [Full Text] [PDF] K. van Besien, F. R. Loberiza Jr, R. Bajorunaite, J. O. Armitage, A. Bashey, L. J. Burns, C. O. Freytes, J. Gibson, M. M. Horowitz, D. J. Inwards, et al. Comparison of autologous and allogeneic hematopoietic stem cell transplantation for follicular lymphoma Blood, November 15, 2003; 102(10): 3521 - 3529. [Abstract] [Full Text] [PDF] D. G. Maloney, A. J. Molina, F. Sahebi, K. E. Stockerl-Goldstein, B. M. Sandmaier, W. Bensinger, B. Storer, U. 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[Abstract] [Full Text] [PDF] E. Bachar-Lustig, S. Reich-Zeliger, and Y. Reisner Anti-third-party veto CTLs overcome rejection of hematopoietic allografts: synergism with rapamycin and BM cell dose Blood, September 15, 2003; 102(6): 1943 - 1950. [Abstract] [Full Text] [PDF] M. B. Maris, D. Niederwieser, B. M. Sandmaier, B. Storer, M. Stuart, D. Maloney, E. Petersdorf, P. McSweeney, M. Pulsipher, A. Woolfrey, et al. HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with hematologic malignancies Blood, September 15, 2003; 102(6): 2021 - 2030. [Abstract] [Full Text] [PDF] M. W. N. Deininger and B. J. Druker Specific Targeted Therapy of Chronic Myelogenous Leukemia with Imatinib Pharmacol. Rev., September 1, 2003; 55(3): 401 - 423. [Abstract] [Full Text] [PDF] J. N. Barker, D. J. Weisdorf, T. E. DeFor, B. R. Blazar, J. S. Miller, and J. E. Wagner Rapid and complete donor chimerism in adult recipients of unrelated donor umbilical cord blood transplantation after reduced-intensity conditioning Blood, September 1, 2003; 102(5): 1915 - 1919. [Abstract] [Full Text] [PDF] P. Corradini, M. Cavo, H. Lokhorst, G. Martinelli, C. Terragna, I. Majolino, P. Valagussa, M. Boccadoro, D. Samson, A. Bacigalupo, et al. Molecular remission after myeloablative allogeneic stem cell transplantation predicts a better relapse-free survival in patients with multiple myeloma Blood, September 1, 2003; 102(5): 1927 - 1929. [Abstract] [Full Text] [PDF] D.C. Taussig, A.J. Davies, J.D. Cavenagh, H. Oakervee, D. Syndercombe-Court, S. Kelsey, J.A.L. Amess, A.Z.S. Rohatiner, T.A. Lister, and M.J. Barnett Durable Remissions of Myelodysplastic Syndrome and Acute Myeloid Leukemia After Reduced-Intensity Allografting J. Clin. Oncol., August 15, 2003; 21(16): 3060 - 3065. [Abstract] [Full Text] [PDF] M. Renga, P. Pedrazzoli, and S. Siena Present results and perspectives of allogeneic non-myeloablative hematopoietic stem cell transplantation for treatment of human solid tumors Ann. Onc., August 1, 2003; 14(8): 1177 - 1184. [Abstract] [Full Text] [PDF] M. Bornhauser, B. Storer, J. T. Slattery, F. R. Appelbaum, H. J. Deeg, J. Hansen, P. J. Martin, G. B. McDonald, W. G. Nichols, J. Radich, et al. Conditioning with fludarabine and targeted busulfan for transplantation of allogeneic hematopoietic stem cells Blood, August 1, 2003; 102(3): 820 - 826. [Abstract] [Full Text] [PDF] T. Fukuda, M. Boeckh, R. A. Carter, B. M. Sandmaier, M. B. Maris, D. G. Maloney, P. J. Martin, R. F. Storb, and K. A. Marr Risks and outcomes of invasive fungal infections in recipients of allogeneic hematopoietic stem cell transplants after nonmyeloablative conditioning Blood, August 1, 2003; 102(3): 827 - 833. [Abstract] [Full Text] [PDF] J. A. Perez-Simon, M. Diez-Campelo, R. Martino, A. Sureda, D. Caballero, C. Canizo, S. Brunet, A. Altes, L. Vazquez, J. Sierra, et al. Impact of CD34+ cell dose on the outcome of patients undergoing reduced-intensity-conditioning allogeneic peripheral blood stem cell transplantation Blood, August 1, 2003; 102(3): 1108 - 1113. [Abstract] [Full Text] [PDF] M. Mohty, J.-O. Bay, C. Faucher, B. Choufi, K. Bilger, O. Tournilhac, N. Vey, A.-M. Stoppa, D. Coso, C. Chabannon, et al. Graft-versus-host disease following allogeneic transplantation from HLA-identical sibling with antithymocyte globulin-based reduced-intensity preparative regimen Blood, July 15, 2003; 102(2): 470 - 476. [Abstract] [Full Text] [PDF] M. Mielcarek, P. J. Martin, W. Leisenring, M. E. D. Flowers, D. G. Maloney, B. M. Sandmaier, M. B. Maris, and R. Storb Graft-versus-host disease after nonmyeloablative versus conventional hematopoietic stem cell transplantation Blood, July 15, 2003; 102(2): 756 - 762. [Abstract] [Full Text] [PDF]

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