Skip to main content
SpringerLink
Log in

Update on non-myeloablative stem cell transplantation for hematologic malignancies

  • Non-myeloablative Stem Cell Transplantation
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

Allogeneic stem cell transplantation is an established treatment modality for a variety of hematologic malignancies. Unfortunately it carries a high risk of complications and toxicities related to the intensive preparative regimen which is traditionally used for pre-transplant myeloablation and the graft versus host disease, which may be life threatening. Thus allogeneic stem cell transplantation has been used only for younger patients with a good performance status, excluding many other potential candidates due to advanced age or comorbid conditions. Non ablative or reduced intensity preparative regimens for allogeneic stem cell transplantation (NST) have been proposed as a strategy that would allow exploiting the graft versus tumor effect of allogeneic transplantation without the toxicity of myelo-ablative therapy. After more than five years of cumulative clinical experience, it is now well established that NST is a feasible treatment option for patients with suboptimal performance status and is mostly effective in slow proliferating malignancies, which gives time for a graft versus malignancy effect to take place. Additionally achievement of stable donor cell engraftment with NSTs provides a platform for adoptive immune cell treatments and may allow to extend indications of stem cell transplantation in the future.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Armitage JO. Bone marrow transplantation.N Engl J Med. 1994;330:827–838.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  3. Burchenal JH, Oettgen HF, Holmberg EAD, Hemphil SC, Reppert JA. Effect of total body irradiation on the transplantability of mouse leukemias.Cancer Res. 1960;20:425.

    PubMed  CAS  Google Scholar 

  4. Barnes DWH, Corp MJ, Loutit JF, Neal FE. Treatment of murine leukaemia with x-rays and homolgous bone marrow. Preliminary communication.Br Med J. 1956;2:626.

    Article  PubMed  CAS  Google Scholar 

  5. Mathe G, Amiel JL, Schwarzenberg L, Cattan A, Schneider M. Adoptive immunotherapy of acute leukemia: experimental and clinical results.Cancer Res. 1965;25:1525–1531.

    PubMed  CAS  Google Scholar 

  6. 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.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  8. Antin JH. Graft-versus-leukemia: no longer an epiphenomenon.Blood. 1993;82:2273–7.

    PubMed  CAS  Google Scholar 

  9. 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 

  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. Kolb HJ, Mittermuller J, Clemm C, et al. Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients.Blood. 1990;76:2462–2465.

    PubMed  CAS  Google Scholar 

  12. Slavin S, Naparstek E, Nagler A, Ackerstein A, Kapelushnik J, Or R. Allogeneic cell therapy for relapsed leukemia after bone marrow transplantation with donor peripheral blood lymphocytes.Exp Hematol. 1995;23:1553–1562.

    PubMed  CAS  Google Scholar 

  13. 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.Blood. 1995; 86:4337–4343.

    PubMed  CAS  Google Scholar 

  14. Ringden O, Horowitz MM, Gale RP, et al. Outcome after allogeneic bone marrow transplant for leukemia in older adults.JAMA. 1993;270:57–60.

    Article  PubMed  CAS  Google Scholar 

  15. Hill GR, Crawford JM, Cooke KR, Brinson YS, Pan L, Ferrara JL. 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 

  16. Slavin S, Strober S, Fuks Z, Kaplan HS. Long term survival of skin allografts in mice treated with fractionated total lymphoid irradiation.Science. 1976;193:1252.

    Article  PubMed  CAS  Google Scholar 

  17. Yu C, Storb R, Mathey B, et al. HLA-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 

  18. Georges GE, Storb R, Thompson JD, et al. Adoptive immunotherapy in canine mixed chimeras after nonmyeloablative hematopoietic cell transplantation.Blood. 2000;95:3262–3269.

    PubMed  CAS  Google Scholar 

  19. Childs R, Chernoff A, Contentin N, et al. Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation.N Engl J Med. 2000;343:750–758.

    Article  PubMed  CAS  Google Scholar 

  20. 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 

  21. Exner BG, Domenick MA, Bergheim M, Mueller YM, Ildstad ST. Clinical applications of mixed chimerism.Ann N Y Acad Sci. 1999;872:377–385.

    Article  PubMed  CAS  Google Scholar 

  22. McSweeney PA, Storb R. Mixed chimerism: preclinical studies and clinical applications.Biol Blood Marrow Transplant. 1999; 5:192–203.

    Article  PubMed  CAS  Google Scholar 

  23. Giralt S, Khouri I, Champlin R. Nonmyeloablative “mini transplants”.Cancer Treat Res. 1999;101:97–108.

    PubMed  CAS  Google Scholar 

  24. Keating MJ, 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. 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 

  26. 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 

  27. Giralt S, Estey E, Albitar M, et al. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy.Blood. 1997;89:4531–4536.

    PubMed  CAS  Google Scholar 

  28. Plunkett W, Saunders PP. Metabolism and action of purine nucleoside analogs.Pharmacol Ther. 1991;49:239–268.

    Article  PubMed  CAS  Google Scholar 

  29. 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.

    PubMed  CAS  Google Scholar 

  30. Maris MB, Sandmeier BM, Niederwieser D, et al. Comparisons of donor chimerism, graft rejection, and GVHD after hematopoietic stem cell transplants (HSCT) from HLA matched siblings and unrelated donors using conditioning with 2 GY TBI with and without Fludarabine [abstract].Blood. 2000;96(Suppl 1):520a.

    Google Scholar 

  31. Sykes M, Saidman SL, Preffer F, et al. Mixed lymphohematopoietic chimerism in adult recipients following non-myeloablative therapy and HLA-matched or mismatched donor bone marrow transplantation, and the effect of donor leukocyte infusions [abstract].Blood. 1998;92(Suppl 1):520a.

    Google Scholar 

  32. Kottaridis PD, Milligan DW, Chopra R, et al. In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation.Blood. 2000;96: 2419–2425.

    PubMed  CAS  Google Scholar 

  33. Roberts TF, Foss F, Schenkein DA, et al. Novel preparative regimen associated with reduced morbidity and mortality following allogeneic bone marrow transplant.Blood. 2000;96: 781a.

    Google Scholar 

  34. Storb R, Yu C, Sandmaier BM, et al. Mixed hematopoietic chimerism after marrow allografts. Transplantation in the ambulatory care setting.Ann N Y Acad. 1999;Sci 872:372–375.

    Article  CAS  Google Scholar 

  35. Giralt S. Non-myeloablative stem cell transplantation in myeloid leukemias-The MD Anderson Cancer Center experience. In: Giralt S, Slavin S, eds. Non-myeloablative transplantation. UK DSP. 2000;59–72.

  36. Giralt S, Thall PF, Khouri I, et al. Melphalan and purine analog-containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation.Blood. 2001; 97:631–637.

    Article  PubMed  CAS  Google Scholar 

  37. Rezvani K, Lalancette M, Szydlo R, et al. Non-myeloablative stem cell transplant (NMSCT) in AML, ALL and MDS: dis-appointing outcome for patients with advanced phase disease [abstract].Blood. 2000(Suppl 1);96:479a.

    Google Scholar 

  38. Parker JE, Shafi T, Mijovic A, et al. Allogeneic stem cell transplantation (SCT) in MDS: interim results of outcome following non-myeloablative conditioning compared to standard preparative regimens [abstract].Blood. 2000(Suppl 1);96:554a.

    Google Scholar 

  39. Champlin RE, Shimoni A, Cohen A, Arlinghaus R, Siciliano M, Giralt S. FLAG-IDA, a nonablative preparative regimen, with allogeneic PBSC transplantation for CML [abstract].Blood. 2000(Suppl 1);96:410a

    Google Scholar 

  40. Slavin S, Nagler A, Shapira M, Aker M, Or R. Non-myeloablative allogeneic stem cell transplantation for the treatment of patients with chronic myeloid leukemia [abstract].Blood. 2000(Suppl 1):96:203a.

    Google Scholar 

  41. Nagler A, Slavin S. Fludarabine and busulfan as non-myeloablative conditioning in high-risk second transplants and using matched unrelated donors. In: Giralt S, Slavin S, eds. Non-myeloablative transplantation. UK DSP, 2000;93–100.

  42. Sandmaier BM, Niederwieser D, McSweeney PA, et al. Induction of molecular remissions in CML with nonmyeloablative HLA-identical sibling allografts [abstract].Blood. 2000(Suppl 1);96:201a.

    Google Scholar 

  43. Sloand EM, Childs RW, Greene A, Phang S, Young NS, Barrett J. Non-myeloablative peripheral blood stem cell transplantation for chronic myelogenous leukemia [abstract].Blood. 2000(Suppl 1);96:783a.

    Google Scholar 

  44. Ehninger G, Kiehl M, Siegert W, et al. Dose reduced conditioning for allografting in 45 patients with CML: a retrospective analysis [abstract].Blood. 2000(Suppl 1);96:783a.

    Google Scholar 

  45. Lalancette M, Rezvani K, Szydlo R, et al. Favorable outcome of non-myeloablative stem cell transplant for CML in first chronic phase; a retrospective study of the European group for blood and marrow transplantation (EBMT) [abstract].Blood. 2000(Suppl 1);96:2340.

    Google Scholar 

  46. van Besien KW, Mehra RC, Giralt SA, et al. Allogeneic bone marrow transplantation for poor-prognosis lymphoma: response, toxicity and survival depend on disease histology.Am J Med 1996;100:299–307.

    Article  PubMed  Google Scholar 

  47. Khouri I, Lee MS, Palmer L, et al. Transplant-lite using fludarabine cyclophosphamide and allogeneic stem cell transplant for low grade lymphoma [abstract].Blood 1999(Suppl 1);94:348a.

    Google Scholar 

  48. Khouri I, Giralt S, Saliba R, et al. ‘Mini’-allogeneic srem cell transplantation for relapsed/refractory lymphomas with aggressive histologies.Proc Am Soc Clin Oncol. 2000;19:47a.

    Google Scholar 

  49. Robinson SP, Mackinnon S, Goldstone AH, et al. Higher than expected transplant-related mortality and relapse following non-myeloablative stem cell transplantation for lymphoma adversely effects progression free survival [abstract].Blood. 2000 (Suppl 1);96:554a.

    Google Scholar 

  50. Schetelig J, Held TK, Bornhuser M, et al. Nonmyeloablative stem cell transplants in chronic lymphocytic leukemia from related and unrelated donors [abstract].Blood. 2000(Suppl 1); 96:200a.

    Google Scholar 

  51. 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 

  52. Lokhorst HM, Schattenberg A, Cornelissen JJ, Thomas LL, Verdonck LF. Donor leukocyte infusions are effective in relapsed multiple myeloma after allogeneic bone marrow transplantation.Blood. 1997;90:4206–4211.

    PubMed  CAS  Google Scholar 

  53. Molina A, Sahebi F, Maloney DG, et al. Non-myeloablative peripheral blood stem cell allografts following cytoreductive autotransplants for the treatment of multiple myeloma [abstract].Blood. 2000(Suppl 1);96:480a.

    Google Scholar 

  54. Lalancette M, Rezvani K, Szydlo R, et al. Excellent outcome of non-myeloablative stem cell transplant for good risk myeloma: the EBMT experience [abstract].Blood. 2000(Suppl 1);96: 204a.

    Google Scholar 

  55. Peggs KS, Williams CD, Chopra R, et al. Non-myeloablative allogeneic transplantation with adjuvant dose-escalated donor lymphocyte infusions for multiple myeloma [abstract].Blood. 2000(Suppl 1);96:781a.

    Google Scholar 

  56. Schaefer H, Bader P, Hebart H, Bamberg M, Kanz L, Einsele H. Mini-allografts as salvage therapy in patients with heavily pretreated multiple myeloma [abstract].Blood. 2000(Suppl 1); 96:306b.

    Google Scholar 

  57. Badros A, Tricot G, Morris C, et al. Significant graft-vs-myeloma effect after non-myeloablative allogeneic transplantation in multiple myeloma [abstract].Blood. 2000(Suppl 1);96: 352b.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Blood and Marrow Transplantation of the University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    S. Giralt

Authors
  1. S. Giralt
    View author publications

    You can also search for this author in PubMed Google Scholar

About this article

Cite this article

Giralt, S. Update on non-myeloablative stem cell transplantation for hematologic malignancies. Int J Hematol 76 (Suppl 1), 176–183 (2002). https://doi.org/10.1007/BF03165241

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03165241

Key words

Search

Navigation