Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects

DOI PDF 被引用文献50件
  • Peter A. McSweeney
    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.
  • Dietger Niederwieser
    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.
  • Judith A. Shizuru
    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.
  • Brenda M. Sandmaier
    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.
  • Arthur J. Molina
    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.
  • David G. Maloney
    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.
  • Thomas R. Chauncey
    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.
  • Theodore A. Gooley
    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.
  • Ute Hegenbart
    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.
  • Richard A. Nash
    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.
  • Jerald Radich
    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.
  • John L. Wagner
    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.
  • Steven Minor
    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.
  • Frederick R. Appelbaum
    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.
  • William I. Bensinger
    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.
  • Eileen Bryant
    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.
  • Mary E. D. Flowers
    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.
  • George E. Georges
    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.
  • F. Carl Grumet
    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.
  • Hans-Peter Kiem
    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.
  • Beverly Torok-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.
  • Cong Yu
    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.
  • Karl G. Blume
    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.
  • 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.

書誌事項

公開日
2001-06-01
DOI
  • 10.1182/blood.v97.11.3390
公開者
American Society of Hematology

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説明

<jats:p>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.</jats:p>

収録刊行物

  • Blood

    Blood 97 (11), 3390-3400, 2001-06-01

    American Society of Hematology

被引用文献 (50)*注記

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