Related and unrelated nonmyeloablative hematopoietic stem cell transplantation for malignant diseases (original) (raw)

Abstract

Patients with advanced hematological malignancies ineligible for conventional myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) due to advanced age or medical contraindications were enrolled in a multi-center study to investigate the safety and efficacy of nonmyeloablative HSCT using a 2 Gy total body irradiation (TBI)-based regimen. A total of 192 patients (median age 55) were treated with HLA-matched sibling peripheral blood stem cell (PBSC) grafts, and 63 patients (median age 53) received a 10 of 10 HLA-antigen matched unrelated donor (URD) HSCT (PBSC graft, n=48; marrow graft, n=15). Diagnoses included multiple myeloma (n=61), myelodysplastic syndrome (n=55), chronic myeloid leukemia (n=31), non-Hodgkin lymphoma (n=31), acute myeloid leukemia (n=28), chronic lymphocytic leukemia (n=24), Hodgkin Disease (n=14). The conditioning regimen was fludarabine 30 mg/m2/d × 3 days and 2 Gy TBI. Ninety-five related HSCT patients received 2 Gy TBI without fludarabine. Postgrafting immunosuppression was combined mycophenolate mofetil and cyclosporine. Transplants were well tolerated with a median of 0 days of hospitalization in the first 60 days for eligible patients. For related HSCT recipients, median follow-up was 289 (100–1188) days. Nonfatal graft rejection occurred in 6.8%. Of those with sustained engraftment, graft-versus-host disease (GVHD) occurred in 49% (33% grade II, 11% grade III, 5% grade IV). Day-100 non-relapse mortality was 6%. Overall, 59% (114/192) of patients were alive. The relapse/disease progression mortality was 18%, and non-relapse mortality was 22%. The projected 2-year survival and progression-free survival were 50% and 40%. For the URD HSCT recipients, median follow-up was 190 (100–468) days. Graft rejection occurred in 27% (17/63) of patients, mostly in recipients of marrow grafts (9/15). Acute GVHD occurred in 63% (50% grade II, 13% grade III) of 46 engrafted patients. Chronic GVHD requiring therapy occurred in 50% of patients. Of the 63 URD HSCT patients, 54% were alive, 37% in CR, 3% PR, and 14% with disease progression or relapse. Related and unrelated nonmyeloablative HSCT is feasible and potentially curative in patients with advanced hematological malignancies who have no other treatment options.

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Authors and Affiliations

  1. Clinical Research Division, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, USA
    George E. Georges, Michael Maris, Brenda M. Sandmaier, David G. Maloney, LyleFeinstein, Thomas R. Chauncey, Marie-Trse Little, Ann E. Woolfrey, Jerald P. Radich & Rainer Storb
  2. Department of Medicine, University of Washington, Seattle, WA, USA
    George E. Georges, Michael Maris, Brenda M. Sandmaier, David G. Maloney, LyleFeinstein, Ann E. Woolfrey, Jerald P. Radich & Rainer Storb
  3. Stanford University, Stanford, CA
    Judith A. Shizuru & Karl G. Blume
  4. University of Leipzig, Leipzig, Germany
    Dietger Niederweiser & Ute Hegenbart
  5. City of Hope National Medical Center, Duarte, CA
    Firoozeh Sahebi & Stephen Forman
  6. Veterans Administration Medical Center, Seattle, WA
    Thomas R. Chauncey
  7. University of Utah, Salt Lake City, UT
    Michael A. Pulsipher
  8. University of Torino, Italy
    Benedetto Bruno
  9. University of Colorado, Denver, CO
    Peter A. McSweeney
  10. Baylor University Medical Center, Dallas, TX, USA
    Edward Agura

Authors

  1. George E. Georges
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  2. Michael Maris
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  3. Brenda M. Sandmaier
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  4. David G. Maloney
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  5. LyleFeinstein
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  6. Dietger Niederweiser
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  7. Judith A. Shizuru
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  8. Peter A. McSweeney
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  9. Thomas R. Chauncey
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  10. Edward Agura
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  11. Marie-Trse Little
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  12. Firoozeh Sahebi
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  13. Ute Hegenbart
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  14. Michael A. Pulsipher
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  15. Benedetto Bruno
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  16. Stephen Forman
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  17. Ann E. Woolfrey
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  18. Jerald P. Radich
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  19. Karl G. Blume
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  20. Rainer Storb
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Georges, G.E., Maris, M., Sandmaier, B.M. et al. Related and unrelated nonmyeloablative hematopoietic stem cell transplantation for malignant diseases.Int J Hematol 76 (Suppl 1), 184–189 (2002). https://doi.org/10.1007/BF03165242

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