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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: J. T. Schiffer, K. Kirby, B. Sandmaier, R. Storb, L. Corey, and M. Boeckh Timing and severity of community acquired respiratory virus infections after myeloablative versus non-myeloablative hematopoietic stem cell transplantation Haematologica, August 1, 2009; 94(8): 1101 - 1108. [Abstract] [Full Text] [PDF] H. E. Kohrt, B. B. Turnbull, K. Heydari, J. A. Shizuru, G. G. Laport, D. B. Miklos, L. J. Johnston, S. Arai, W.-K. Weng, R. T. Hoppe, et al. 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Risks and outcomes of idiopathic pneumonia syndrome after nonmyeloablative and conventional conditioning regimens for allogeneic hematopoietic stem cell transplantation Blood, October 15, 2003; 102(8): 2777 - 2785. [Abstract] [Full Text] [PDF] R. Wong, S. A. Giralt, T. Martin, D. R. Couriel, A. Anagnostopoulos, C. Hosing, B. S. Andersson, P. Cano, M. Shahjahan, C. Ippoliti, et al. Reduced-intensity conditioning for unrelated donor hematopoietic stem cell transplantation as treatment for myeloid malignancies in patients older than 55 years Blood, October 15, 2003; 102(8): 3052 - 3059. [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. 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