Skip to main content
SpringerLink
Log in

Non Myeloablative “Mini Transplants”

  • Chapter
Advances in Allogeneic Hematopoietic Stem Cell Transplantation

Part of the book series: Cancer Treatment and Research ((CTAR,volume 101))

Abstract

High dose chemo-radiotherapy with allogeneic bone marrow transplantation (BMT) is an effective therapy for patients with hematologic malignancies (1,2). The curative potential of this procedure is mediated in part by an immune mediated graft-versus-leukemia effect (3-8). Direct evidence of this effect is the reinduction of remission obtained after infusions of donor lymphocytes in patients who have relapsed after an allogeneic progenitor cell transplant.(9-13) Responses are more frequent in patients with chronic myelogenous leukemia (CML), but have also been observed in patients with acute myelogenous leukemia (AML), chronic lymphocytic leukemia (CLL), myeloma and lymphoma relapsing after allogeneic BMT (14-16).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Gale RP, Champlin RE. How does bone marrow transplantation cure leukemia? Lancet. 1984;2: 28–30.

    Article  PubMed  CAS  Google Scholar 

  2. Bortin M, Horowitz M, Gale R, et al: Changing trends in allogeneic bone marrow transplantation for leukemia in the 1980’s. JAMA, 1992; 268: 607–612.

    Article  PubMed  CAS  Google Scholar 

  3. Weiden PL, Sullivan KM, Flournoy N, Storb R, Thomas ED, The Seattle Marrow Transplant Team. Antileukemic effect of chronic graft-versus-host disease: Contribution to improved survival after allogeneic marrow transplantation. NEJM. 1981;304: 1529–1533.

    Article  PubMed  CAS  Google Scholar 

  4. Horowitz MM, Gale RP, Sondel PM, et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood. 1990;75: 555–562.

    PubMed  CAS  Google Scholar 

  5. Sullivan KM, Storb R, Buckner CD, et al. Graft-versus-host disease as adoptive immunotherapy in patients with advanced hematologic neoplasms. N Engl J Med. 1989;320: 828–834.

    Article  PubMed  CAS  Google Scholar 

  6. Sullivan KM, Weiden PL, Storb R, et al. Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia. Blood. 1989;73: 1720–1728.

    PubMed  CAS  Google Scholar 

  7. Goldman JM, Gale RP, Bortin MM, et al. Bone marrow transplantation for chronic myelogenous leukemia in chronic phase: increased risk of relapse associated with T-cell depletion.. Ann Intern Med. 1988;108: 806–814.

    PubMed  CAS  Google Scholar 

  8. Gale RP, Horowitz MM, Ash RC, et al. Identical-twin bone marrow transplants for leukemia. Ann Intern Med.1994;120: 646–652.

    PubMed  CAS  Google Scholar 

  9. Kolb HJ, Schattenberg A, Goldman JM, et al. Graft-vs-leukemia effect of donor lymphocyte transfusions in marrow grafted patients.. Blood. 1995;86: 2041–2050.

    PubMed  CAS  Google Scholar 

  10. Van Rhee F, Lin F, Cullis JO, et al. Relapse of chronic myeloid leukemia after allogeneic bone marrow transplant: The case for giving donor leukocyte transfusions before the onset of hematologic relapse. Blood. 1994;83: 3377–3383.

    PubMed  Google Scholar 

  11. Mackinnon S, Papadopoulos EB, Carabasi MH, et al. Adoptive immunotherapy evaluating escalating doses of donor leukeocytes for relapse of chronic myeloid leukemia after bone marrow transplantation: separation of graft-versus-leukemia responses from graft-versus-host disease.. Blood. 1995;86: 1261–1268.

    PubMed  CAS  Google Scholar 

  12. Cullis JO, Jiang YZ, Schwarer AP, Hughes TP, Barrett AJ, Goldman JM. Donor leukocyte infusions for chronic myeloid leukemia in relapse after allogeneic bone marrow transplantation. Blood. 1992;79: 1379–1381.

    PubMed  CAS  Google Scholar 

  13. Drobyski WR, Keever CA, Roth MS, et al. Salvage immunotherapy using donor leukocyte infusions as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation: Efficacy and toxicity of a defined T-cell dose. Blood. 1993;82: 2310–2318.

    PubMed  CAS  Google Scholar 

  14. Tricot G, Vesole DH, Jagannath S, Hilton J, Munshi N, Barlogie B. Graft-versus-myeloma effect: Proof of principle. Blood. 1996;87: 1196–1198.

    PubMed  CAS  Google Scholar 

  15. Rondon G, Giralt S, Huh Y, et al. Graft-versus-leukemia effect after allogeneic bone marrow transplantation for chronic lymphocytic leukemia. Bone Marrow Transplantation. 1996;18: 669–672.

    PubMed  CAS  Google Scholar 

  16. Collins R, Shpilberg O, Drobyski W, et al: Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplant. J Clin Oncol, 1997; 15: 433–444.

    PubMed  Google Scholar 

  17. Ferrara JL, Deeg HJ. Mechanisms of disease: Graft-versus-host disease. N Engl J Med. 1991;324: 667–674.

    Article  PubMed  CAS  Google Scholar 

  18. Holler E, Kolb H, Moller A, et al: Increased serum levels of tumor necrosis factor a precede major complications of bone marrow transplantation. Blood, 1990;7: 1011–1016.

    Google Scholar 

  19. Hill G, Crawford J, Cooke K, Brinson Y, Pan L, Ferrrara J: Total body irradiation and acute graft versus host disease: The role of gastrointestinal damage and inflammatory cytokines. Blood, 1997; 90: 3204–3213.

    PubMed  CAS  Google Scholar 

  20. Van Bekkum D: Conditioning regimens for marrow grafting. Semin Hematol, 1984;21: 81–90.

    PubMed  Google Scholar 

  21. Yu C, Storb R, Mathey B, et al: DLA-identical bone marrow grafts after low dose total body irradiation: Effects of high dose corticosteroids and cyclosporine on engraftment. Blood, 1995; 86: 4376–4381.

    PubMed  CAS  Google Scholar 

  22. Storb R, Yu C, Wagner J, et al: Stable mixed hematopoietic chimerism in DLA-identical littermate dogs given sublethal total body irradiation before and pharmacological immunosuppression after marrow transplantation. Blood, 1997; 89: 3048–3054.

    PubMed  CAS  Google Scholar 

  23. Keating MJ, O’Brien S, Robertson LE, et al. The expanding role of fludarabine in hematologic malignancies. Leuk Lymphoma. 1994;14 Suppl. 2: 11–16.

    Article  PubMed  Google Scholar 

  24. Keating M, Kantarjian H, Talpaz M, et al: Fludarabine: A new agent with major activity against chronic lymphocytic leukemia. Blood, 1989; 74: 19–25.

    PubMed  CAS  Google Scholar 

  25. Redman J, Cabanillas F, Velasquez W, et al: Phase II trial of fludarabine phosphate in lymphoma: an effective new agent in low grade lymphoma. J Clin Oncol, 1992; 10: 790–794.

    PubMed  CAS  Google Scholar 

  26. Goodman E, Fiedor P, Fein S, et al: Fludarabine phosphate and 2 chlorodeoxyadenosine:Immuno-suppressive DNA synthesis inhibitors with potential application in islet allo-xenotransplantation. Transplantation Proc, 1995; 27: 3293–3294.

    CAS  Google Scholar 

  27. Plunkett W, Sanders P: Metabolism and action of purine nucleoside analogs. Pharmacol Ther, 1991; 49: 239–245.

    Article  PubMed  CAS  Google Scholar 

  28. Gandhi V, Estey E, Keating MJ, Plunkett W. Fludarabine potentiates metabolism of cytarabine in patients with acute myelogenous leukemia during therapy. J Clin Oncol. 1993;11: 116–124.

    PubMed  CAS  Google Scholar 

  29. Li L, Glassman A, Keating M, Stros M, Plunkett W, Yang L: Fludarabine triphosphate inhibits nucleotide excision repair of cisplatin-induced DNA adducts in vitro. Cancer Res 1997; 57: 1487–1494.

    PubMed  CAS  Google Scholar 

  30. Estey E, Plunkett W, Gandhi V, Rios MB, Kantarjian H, Keating MJ. Fludarabine and arabinosylcytosine therapy of refractory and relapsed acute myelogenous leukemia. Leuk Lymphoma. 1993;9: 343–350.

    Article  PubMed  CAS  Google Scholar 

  31. Giralt S, Estey E, Van Besien K, et al. Engraftment of allogeneic hematopoietic progenitor cells with purine analog containing chemotherapy: harnessing graft-vs-leukemia without myeloablative therapy.. Blood 1997; 89(12): 4531–4536.

    PubMed  CAS  Google Scholar 

  32. Giralt S, Gajewski J, Khouri I, et al: Induction of graft-vs-leukemia as primary treatment of chronic myelogenous leukemia: Blood 1997; 90: 418a.

    Google Scholar 

  33. Khouri I, Keating MJ, Przepiorka D, et al. Engraftment and induction of GVL with fludarabine-based non-ablative preparative regimen in patients with chronic lymphocytic leukemia.. Blood. 1996;88 (suppl l): 301a.

    Google Scholar 

  34. Bensinger W, Buckner C, Clift R, et al: A phase I study of busulfan and cyclophosphamide in preparation for allogeneic marrow transplant for patients with multiple myeloma. J Clin Oncol 1992; 10: 1492–1497.

    PubMed  CAS  Google Scholar 

  35. Bjorkstrand B, Ljungman P, Svensson H, et al: Allogeneic bone marrow transplantation versus autologous stem cell transplantation in multiple myeloma: A retrospective case-matched study from the European Group for Blood and Marrow Transplantation. Blood 1996; 88: 4711–4718.

    PubMed  CAS  Google Scholar 

  36. Lokhorst H, Schattenberg A, Cornelissen J, Thomas L, Verdonck L: Donor leukocyte infusions are effective in relapsed multiple myeloma after allogeneic bone marrow transplantation. Blood 1997; 90: 4206–4211.

    PubMed  CAS  Google Scholar 

  37. Lokhurst K, Meuwissen O, Verdonck L, Dekker A, High risk multiple myeloma treated with high dose melphalan. J Clin Oncol 1992; 10: 47–51.

    Google Scholar 

  38. Slavin S, Nagler A, Naparstek E, et al: Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood 1998; 91: 756–763.

    PubMed  CAS  Google Scholar 

  39. Giralt S, Cohen A, Mehra R, et al: Preliminary results of fludarabine/melphalan or 2CDA/melphalan as preparative regimens for allogeneic progenitor cell transplantation in poor candidates for conventional myeloablative conditioning. Blood 1997; 90: 417a.

    Google Scholar 

  40. Champlin R, Ho W, Gajewski J, et al. Selective depletion of CD8+ T lymphocytes for prevention of graft-versus-host disease after allogeneic bone marrow transplantation. Blood. 1990;76: 418–423.

    PubMed  CAS  Google Scholar 

  41. Nimer SD, Giorgi J, Gajewski JL, et al. Selective depletion of CD8+ cells for prevention of graft-versus-host disease after bone marrow transplantation: A randomized controlled trial. Transplantation. 1994;57: 82–87.

    Article  PubMed  CAS  Google Scholar 

  42. Giralt S, Hester J, Huh Y, et al. CD8+ depleted donor lymphocyte infusion as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation: graft vs leukemia without graft vs. host disease.. Blood. 1995;86: 4337–4343.

    PubMed  CAS  Google Scholar 

  43. Alyea E, Soiffer R, Canning C, et al: Toxicity and efficacy of defined doses of CD4+ donor lymphocytes for treatment of relapse after allogeneic bone marrow transplant. Blood 1998; 91: 3671–3680.

    PubMed  CAS  Google Scholar 

  44. Bordignon C, Bonini C, Verzeletti S, et al. Transfer of the HSV-tk gene into donor peripheral blood lymphocytes for in vivo modulation of donor antitumor immunity after allogeneic bone marrow transplantation. Hum Gene Ther. 1995;6: 813–819.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Sergio Giralt M.D., Issa Khouri M.D. & Richard Champlin M.D.

Authors
  1. Sergio Giralt M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Issa Khouri M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Richard Champlin M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Northwestern University Medical Center, Chicago, USA

    Richard K. Burt  & Mary M. Brush  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Springer Science+Business Media New York

About this chapter

Cite this chapter

Giralt, S., Khouri, I., Champlin, R. (1999). Non Myeloablative “Mini Transplants”. In: Burt, R.K., Brush, M.M. (eds) Advances in Allogeneic Hematopoietic Stem Cell Transplantation. Cancer Treatment and Research, vol 101. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4987-1_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-4987-1_5

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7264-6

  • Online ISBN: 978-1-4615-4987-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation