Advertisement

Immunologic Research

, Volume 28, Issue 1, pp 1–11 | Cite as

Therapeutic applications of non-myeloablative hematopoietic stem cell transplantation in malignant disease

  • William J. Hogan
  • Rainer Storb
Article

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) currently provides the only chance of curative therapy for many patients with hematological malignancies. Owing to the excess morbidity and mortality observed in less robust patients, this approach has traditionally been limited to younger patients without significant medical co-morbidities. Given the age profiles of patients with candidate hematological malignancies, a majority of patients are therefore ineligible for myeloablative therapy. Over the past few years the ability to achieve hematopoietic stem cell engraftment using immunosuppressive but non-myeloablative conditioning regimens has made it possible to consider a much broader group of patients for allogeneic HSCT. The discovery that the hematopoietic graft itself can contribute to the eradication of malignant cells through a graft-versus-malignancy (GVM) effect, independent of the conditioning regimen, has led to investigation of reduced intensity conditioning regimens for a variety of malignant diseases. Over the past few years there has been a dramatic increase in the number of patients undergoing reduced intensity conditioning for both malignant and nonmalignant conditions. This review will focus only on the use of such therapy for malignant disease.

Key Words

Non-myeloablative Hematopoietic Stem cell transplantation 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Thomas ED, Blume KG, Forman SJ: Hematopoietic Cell Transplantation, 2nd edition, Blackwell Science, Inc., 1999; pp. 942.Google Scholar
  2. 2.
    Weiden PL, Flournoy N, Thomas ED: Antileukemic effect of graftversus-host disease in human recipients of allogeneic-marrow grafts. New Engl J Med 1979;300:1068–1073.PubMedCrossRefGoogle Scholar
  3. 3.
    Weiden PL, Sullivan KM, Flournoy N, Storb R, Thomas ED: Antileukemic effect of chronic graft-versus-host disease: contribution to improved survival after allogeneic marrow transplantation. N Engl J Med 1981;304:1529–1533.PubMedCrossRefGoogle Scholar
  4. 4.
    Gale RP, Horowitz MM, Ash RC, et al: Identical-twin bone marrow transplants for leukemia. Ann Inter Med 1994;120:646–652.Google Scholar
  5. 5.
    Kolb HJ, Mittermuller J, Clemm C, et al: Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood 1990;76:2462–245.PubMedGoogle Scholar
  6. 6.
    Kolb HJ, Schattenberg A, Goldman JM, et al: Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. European Group for Blood and Marrow Transplantation Working Party Chronic Leukemia. Blood 1995;86:2041–2050.Google Scholar
  7. 7.
    Ueno NT, Rondon G, Mirza NQ, et al: Allogeneic peripheral-blood progenitor-cell transplantation for poor-risk patients with metastatic breast cancer. J Clin Oncol 1998; 16:986–993.PubMedGoogle Scholar
  8. 8.
    Khouri IF, Keating M, Korbling M, et al: Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies. J Clin Oncol 1998; 16:2817–2824.PubMedGoogle Scholar
  9. 9.
    Childs R, Chernoff A, Contentin N, et al: Regression of metastatic reral-cell carcinoma after nommyeloablative allogeneic peripheral-blood stem-cell transplantation. N Engl J Med 2000;343:750–758.PubMedCrossRefGoogle Scholar
  10. 10.
    Storb RF, Champlin R, Riddell SR, Murata M, Bryant S, Warren EH: Non-myeloablative transplants for malignant disease. Hematology, 2001Google Scholar
  11. 11.
    van Besien KW, de Lima M, Giralt SA, et al: Management of lymphoma recurrence after allogeneic transplantation: the relevance of graft-versus-lymphoma effect. Bone Marrow Transplantation 1997;19:977–982.PubMedCrossRefGoogle Scholar
  12. 12.
    Storb R, Yu C, Deeg HJ, et al: Current and future preparative regimens for bone marrow transplantation in thal assemia. Ann NY Acad Sci 1998;850:276–287.PubMedCrossRefGoogle Scholar
  13. 13.
    Slavin S, Nagler A, Naparstek E, et al: Nomnyeloablative stem cell transplantation and cell therapy as analterrative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood 1998; 91:756–763.PubMedGoogle Scholar
  14. 14.
    Yu C, Storb R, Mathey B, Deeg HJ, 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.PubMedGoogle Scholar
  15. 15.
    Storb R, Yu C, Wagner JL, 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.PubMedGoogle Scholar
  16. 16.
    McSweeney PA, Niederwieser D, Shizuru JA, et al: Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graftversus-tumor effects. Blood 2001; 97:3390–3400.PubMedCrossRefGoogle Scholar
  17. 17.
    Sandmaier B, Maloney D, Gooley T, et al: Nonmyeloablative hematopoietic stem cell transplants (HSCT) from HLA-matched related donors for patients with hematologic malignancies: clinical results of a TBI-based conditioning regimen. Blood 2001;98: Abstract 3093.Google Scholar
  18. 18.
    Khouri IF, Saliba RM, Giralt SA, et al: Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versushost disease, and treatment-related mortality. Blood 2001;98:3595–3599.PubMedCrossRefGoogle Scholar
  19. 19.
    van Besien K, Sobocinski KA, Rowlings PA, et al: Allogeneic bone marrow transplantation for low-grade lymphoma. Blood 1998;92:1832–1836.PubMedGoogle Scholar
  20. 20.
    Berdeja JG, Flinn IW: New approaches to blood and marrow transplantation for patients with low-grade lymphomas. Curr Opinion Oncol 2001;13:335–341.CrossRefGoogle Scholar
  21. 21.
    Flowers CR, Maloney DG, Sandmaier BM, et al: Allogeneic hematopoietic stem cell transplantation with nonmyeloablative conditioning for patients with chronic lymphocytic leukemia. Blood 2001;98:Abstract 1755.Google Scholar
  22. 22.
    Martinez C, Carreras E, Rovira M, et al: Patients with mantle-cell lymphoma relapsing after autologous stem cell transplantation may be rescued by allogeneic transplantation. Bone Marrow Transplantation 2000;26:677–679.PubMedCrossRefGoogle Scholar
  23. 23.
    Khouri IF, Lee MS, Romaguera J, et al: Allogeneic hematopoietic transplantation for mantle-cell lymphoma: molecular remissions and evidence of graft-versus-malignancy. Ann Oncol 1999;10:1293–1299.PubMedCrossRefGoogle Scholar
  24. 24.
    Khouri I, Saliba R, Younes A, et al: Allogeneic transplantation for poor risk mantle cell lymphoma (MCL): chemosensitivity predicts superior outcome. Blood 2001;98:Abstract 1745.Google Scholar
  25. 25.
    Giralt S, Estey E, Albitar M, et al: Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versusleukemia without myeloablative therapy. Blood 1997;89:4531–4536.PubMedGoogle Scholar
  26. 26.
    Hegenbart JJ, Sandmaier B, Lange T, et al: Graft versus leukemia effect after related and unrelated allogeneic hematopoietic stem cell transplants (HSCT) in patients with acute myeloid leukemia (AML) following minimal conditioning. Blood 2001;98:Abstract 2814.Google Scholar
  27. 27.
    Radich JP, Gooley T, Clift R, Bryant E, Flowers ME, Appelbaum FR: Allogeneic-related transplantation for chronic phase chronic myeloid leukemia (CML) using a targeted busulfan and cytoxan preparative regimen. Blood 2001; 98:Abstract 3239.Google Scholar
  28. 28.
    Hansen JA, Gooley TA, Martin PJ, et al: Bone marrow transplants from unrelated donors for patients with chronic myeloid leukemia. N Engl J Med 1998;338:962–968.PubMedCrossRefGoogle Scholar
  29. 29.
    Goldman JM, Druker BJ: Chronic myeloid leukemia: current treatment options. Blood 2001;98:2039–2042.PubMedCrossRefGoogle Scholar
  30. 30.
    Bacigalupo A: Hematopoieticstem cell transplants after reduced intensity conditioning regimen (RI-HSCT): report of a workshop of the European group for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplantation 2000;25:803–805.PubMedCrossRefGoogle Scholar
  31. 31.
    Sandmaier BM, Hegenbart U, Shizuru J, et al: Nonmyeloablative hematopoietic stem cell transplantation (HSCT) from HLA-identical siblings for treatment of chronic myelogenous leukemia (CML): induction of molecular remissions. Blood 2001;98: Abstract 5259.Google Scholar
  32. 32.
    Elmaagacli AH, Rumkel K, Steckel N, et al: A comparison of chimerism and minimal residual disease between four different allogeneic transplantation methods in patients with chronic myelogenous leukemia in first chronic phase. Bone Marrow Transplantation 2001;27:809–815.PubMedCrossRefGoogle Scholar
  33. 33.
    Badros A, Barlogie B, Morris C, et al: High response rate in refractory and poor-risk multiple myeloma after allotransplantation using a nonmyeloablative conditioning regimen and donor lymphocyte infusions. Blood 2001;97:2574–2579.PubMedCrossRefGoogle Scholar
  34. 34.
    Maloney DG, Sahebi F, Stockerl-Goldstein KE, et al: Combining an allogeneic graft-vs-myeloma effect with high-dose autologous stem cell rescue in the treatment of multiple myeloma. Blood 2001;98: Abstract 1822.Google Scholar
  35. 35.
    Maris M, Niederwieser D, Sandmaier B, et al: Nonmyeloablative hematopoeitic stem cell transplants (HSCT) using 10/10 HLA antigen matched unrelated donors (URDs) for patients with advanced hematologic malignancies ineligible for conventional HSCT. Blood 2001; 98:Abstract 3563.Google Scholar
  36. 36.
    Junghanss C, Marr KA, Carter RA, et al: Incidence of Bacterial and Fungal Infections after Nonmyeloablative Compared to Myeloablative Allogenic Hematopoietic Stem Cell Transplantation (HSCT). Blood 2001;98: Abstract 2000.Google Scholar
  37. 37.
    Costa S, Anaissie E, Badros A, et al: High rate of CMV activation without disease following mini-allograft peripheral stem cell transplantation (Miniallo Tx). Blood 2000;96:337b, Abstract 5206.Google Scholar
  38. 38.
    Junghanss C, Boeckh M, Carter RA, et al: Incidence and Outcome of cytomegalovirus infections following non-myeloablative compared to myeloablative allogeneic stem cell transplantation, a matched control study. Blood 2002;99(b):1978–1985.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2003

Authors and Affiliations

  • William J. Hogan
    • 1
    • 2
  • Rainer Storb
    • 1
    • 2
  1. 1.Program in Transplantation Biology, Clinical Research Division, Fred Hutchinson Cancer Research CenterUniversity of Washington, School of MedicineSeattle
  2. 2.Department of Medicine, Division of OncologyUniversity of Washington, School of MedicineSeattle

Personalised recommendations