Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Allogeneic hematopoietic stem-cell transplantation: the next generation of therapy for metastatic renal cell cancer

Abstract

The management of metastatic renal cell carcinoma (mRCC) remains a therapeutic challenge; less than 10% of patients survive for longer than 5 years. The resistance of renal cancer to chemotherapy may be explained by high levels of the multidrug resistance gene, MDR1. Immune-based treatments for renal cancer have been explored because of their unusual susceptibility to immunological assault. However, response rates to cytokines such as interleukin-2 and interferon-α have ranged from only 10% to 20%, prompting other immunotherapy approaches, such as allogeneic stem-cell transplantation, to be investigated. Several clinical trials have provided evidence of partial or complete disease regression in refractory mRCC following nonmyeloablative stem-cell transplantation. This effect is because of a donor antimalignancy effect mediated by immunocompetent donor T cells, called graft-versus-tumor effect. Unfortunately, less than 30% of patients who could have this procedure will have a human-leukocyte-antigen-compatible sibling, and attention is focusing on alternative donors such as matched unrelated donors and partially mismatched related donors. Despite the improved safety of nonmyeloablative conditioning regimens, transplant-related toxic effects (particularly graft-versus-host disease) remain obstacles to the safe and effective use of this treatment. Regardless of these limitations, innovative approaches have attempted to harness the potential of the graft-versus-tumor effect in mRCC and other solid tumors.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Cancer Research UK (2004) Statistics. [http://www.cruk.co.uk/aboutcancer/statistics/incidence] (accessed 16 September 2004)

  2. Vogelzang NJ and Stadler WM (1998) Kidney cancer. Lancet 352: 1691–1696

    Article  CAS  Google Scholar 

  3. Motzer RJ et al. (1996) Renal cell carcinoma. N Engl J Med 335: 865–875

    Article  CAS  Google Scholar 

  4. Kavolius JP et al. (1998) Resection of metastatic renal cell carcinoma. J Clin Oncol 16: 2261–2266

    Article  CAS  Google Scholar 

  5. Yagoda A et al. (1995) Chemotherapy for advanced renal-cell carcinoma: 1983–1993. Semin Oncol 22: 42–60

    CAS  PubMed  Google Scholar 

  6. Motzer RJ and Russo P (2000) Systemic therapy for renal cell carcinoma. J Urol 163: 408–417

    Article  CAS  Google Scholar 

  7. Hrushesky WJ et al. (1990) Circadian-shaped infusions of floxuridine for progressive metastatic renal cell carcinoma. J Clin Oncol 8: 1504–1513

    Article  CAS  Google Scholar 

  8. Yagoda A et al. (1993) Cytotoxic chemotherapy for advanced renal cell carcinoma. Urol Clin North Am 20: 303–321

    CAS  PubMed  Google Scholar 

  9. Fossa SD et al. (1992) Vinblastine in metastatic renal cell carcinoma: EORTC phase II trial 30882. The EORTC Genitourinary Group. Eur J Cancer 28A: 878–880

    Article  CAS  Google Scholar 

  10. Milowsky MI and Nanus DM (2003) Chemotherapeutic strategies for renal cell carcinoma. Urol Clin North Am 30: 601–609

    Article  Google Scholar 

  11. Amato RJ (2000) Chemotherapy for renal cell carcinoma. Semin Oncol 27: 177–186

    CAS  PubMed  Google Scholar 

  12. Klein EA (1989) The multidrug resistance gene in renal cell carcinoma. Semin Urol 7: 207–214

    CAS  PubMed  Google Scholar 

  13. Fojo AT et al. (1987) Expression of a multidrug-resistance gene in human tumors and tissues. Proc Natl Acad Sci USA 84: 265–269

    Article  CAS  Google Scholar 

  14. Naito S et al. (1993) Expression of P-glycoprotein and multidrug resistance in renal cell carcinoma. Eur Urol 24: 156–160

    Article  CAS  Google Scholar 

  15. Volm M et al. (1992) Expression of several resistance mechanisms in untreated human kidney and lung carcinomas. Anticancer Res 12: 1063–1067

    CAS  PubMed  Google Scholar 

  16. Bumpus HC (1928) The apparent disappearance of pulmonary metastasis in a case of hypernephroma following nephrectomy. J Urol 20: 185

    Article  Google Scholar 

  17. Fairlamb DJ (1981) Spontaneous regression of metastases of renal cancer: a report of two cases including the first recorded regression following irradiation of a dominant metastasis and review of the world literature. Cancer 47: 2102–2106

    Article  CAS  Google Scholar 

  18. Albini A et al. (2000) Inhibition of angiogenesis and vascular tumor growth by interferon-producing cells: a gene therapy approach. Am J Pathol 156: 1381–1393

    Article  CAS  Google Scholar 

  19. Wirth MP (1993) Immunotherapy for metastatic renal cell carcinoma. Urol Clin North Am 20: 283–295

    CAS  PubMed  Google Scholar 

  20. Minasian LM et al. (1993) Interferon alfa-2a in advanced renal cell carcinoma: treatment results and survival in 159 patients with long-term follow-up. J Clin Oncol 11: 1368–1375

    Article  CAS  Google Scholar 

  21. Neidhart JA et al. (1991) Vinblastine fails to improve response of renal cancer to interferon alfa-n1: high response rate in patients with pulmonary metastases. J Clin Oncol 9: 832–836

    Article  CAS  Google Scholar 

  22. Rosenberg SA et al. (1994) Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. JAMA 271: 907–913

    Article  CAS  Google Scholar 

  23. Negrier S et al. (1998) Recombinant human interleukin-2, recombinant human interferon alfa-2a, or both in metastatic renal-cell carcinoma. Groupe Francais d'Immunotherapie. N Engl J Med 338: 1272–1278

    Article  CAS  Google Scholar 

  24. Rosenberg SA (2001) Progress in human tumour immunology and immunotherapy. Nature 411: 380–384

    Article  CAS  Google Scholar 

  25. Weiden PL et al. (1981) Antileukemic effect of chronic graft-versus-host disease: contribution to improved survival after allogeneic marrow transplantation. N Engl J Med 304: 1529–1533

    Article  CAS  Google Scholar 

  26. Gale RP and Champlin RE (1984) How does bone marrow transplantation cure leukaemia? Lancet 2: 28–30

    Article  CAS  Google Scholar 

  27. Kolb HJ et al. (1990) Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukaemia in marrow transplant patients. Blood 76: 2462–2465

    CAS  PubMed  Google Scholar 

  28. Kolb HJ et al. (1995) Graft-versus-leukemia effect of donor lymphocyte tranfusions in marrow grafted patients: European Group for Blood and Marrow Transplantation Working Party Chronic Leukemia. Blood 86: 2041–2050

    CAS  PubMed  Google Scholar 

  29. Eibl B et al. (1996) Evidence for a graft-versus-tumor effect in a patient treated with marrow ablative chemotherapy and allogeneic bone marrow transplantation for breast cancer. Blood 88: 1501–1508

    CAS  PubMed  Google Scholar 

  30. Ueno NT et al. (1998) Allogeneic peripheral-blood progenitor-cell transplantation for poor-risk patients with metastatic breast cancer. J Clin Oncol 16: 986–993

    Article  CAS  Google Scholar 

  31. Slavin S et al. (1998) Nonmyeloablative stem cell transplantation and cell therapy as alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and non-malignant hematologic diseases. Blood 91: 756–763

    CAS  PubMed  Google Scholar 

  32. Corradini P et al. (2002) Reduced-intensity conditioning followed by allografting of hematopoietic cells can produce clinical and molecular remissions in patients with poor-risk hematologic malignancies. Blood 99: 75–82

    Article  CAS  Google Scholar 

  33. Caignard A et al. (1996) In situ demonstration of renal cell carcinoma-specific T-cell clones. Int J Cancer 66: 564–570

    Article  CAS  Google Scholar 

  34. Jantzer P and Schendel DJ (1998) Human renal cell carcinoma antigen-specific CTLs: antigen-driven selection and long-term persistence in vivo. Cancer Res 58: 3078–3086

    CAS  PubMed  Google Scholar 

  35. Childs R et al. (2000) Regression of metastatic renal cell carcinoma after non-myeloablative allogeneic peripheral-blood stem cell transplantation. N Engl J Med 343: 750–758

    Article  CAS  Google Scholar 

  36. Rini BI et al. (2002) Allogeneic stem-cell transplantation of renal cell cancer after nonmyeloablative chemotherapy: feasibility, engraftment, and clinical results. J Clin Oncol 20: 2017–2024

    Article  Google Scholar 

  37. Pedrazzoli P et al. (2002) Allogeneic blood stem cell transplantation after a reduced-intensity, preparative regimen: a pilot study in patients with refractory malignancies. Cancer 94: 2409–2415

    Article  Google Scholar 

  38. Bregni M et al. (2002) Nonmyeloablative conditioning followed by hematopoietic cell allografting and donor lymphocyte infusions for patients with metastatic renal and breast cancer. Blood 99: 4234–4236

    Article  CAS  Google Scholar 

  39. Bregni M et al. (2003) Graft versus tumor effect following reduced intensity allogeneic stem cell transplantation in renal cell cancer: on behalf of the EBMT Solid Tumor Working Party [abstract]. Blood 102: 198

    Google Scholar 

  40. Blaise D et al. (2004) Reduced-intensity preparative regimen and allogeneic stem cell transplantation for advanced solid tumors. Blood 103: 435–441

    Article  CAS  Google Scholar 

  41. Drachenberg D and Childs RW (2003) Allogeneic stem cell transplantation as immunotherapy for renal cell carcinoma: from immune enhancement to immune replacement. Urol Clin North Am 30: 611–622

    Article  Google Scholar 

  42. Maloney DG et al. (2002) Non-myeloablative transplantation. Hematology (Am Soc Hematol Educ Program) 392–421

  43. Nimer SD et al. (1994) Selective depletion of CD8+ cells for prevention of graft-versus-host disease after bone marrow transplantation: a randomized controlled trial. Transplantation 57: 82–87

    Article  CAS  Google Scholar 

  44. Giralt S et al. (2001) Melphalan and purine analog-containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation. Blood 97: 631–637

    Article  CAS  Google Scholar 

  45. Chakraverty R et al. (2002) Limiting transplantation-related mortality following unrelated donor stem cell transplantation by using a nonmyeloablative conditioning regimen. Blood 99: 1071–1078

    Article  CAS  Google Scholar 

  46. Nagler A et al. (2001) Low-intensity conditioning is sufficient to ensure engraftment in matched unrelated bone marrow transplantation. Exp Hematol 29 362–370

    Article  CAS  Google Scholar 

  47. Bornhauser M et al. (2001) Dose-reduced conditioning and allogeneic hematopoietic stem cell transplantation from unrelated donors in 42 patients. Clin Cancer Res 7: 2254–2262

    CAS  PubMed  Google Scholar 

  48. Hentschke P et al. (2003) Low-intensity conditioning and hematopoietic stem cell transplantation in patients with renal and colon carcinoma. Bone Marrow Transplant 31: 253–261

    Article  CAS  Google Scholar 

  49. Sykes M et al. (1999) Mixed lymphohaemopoietic chimerism and graft-versus-lymphoma effects after non-myeloablative therapy and HLA-mismatched bone-marrow transplantation. Lancet 353: 1755–1759

    Article  CAS  Google Scholar 

  50. Koh LP et al. (2002) Campath-1H, T cell depleted nonmyeloablative peripheral blood stem cell transplantation from 3-6/6 HLA matched family members [abstract]. Blood 100: 2512

    Google Scholar 

  51. Satoh M et al. (2004) Haploidentical, non-myeloablative stem cell transplantation for advanced renal cell cancer. Lancet Oncol 5: 125–126

    Article  Google Scholar 

  52. Miyakoshi S et al. (2004) Successful engraftment after reduced-intensity umbilical cord blood transplantation for adult patients with advanced hematological diseases. Clin Cancer Res 10: 3586–3592

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Manit Arya.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Arya, M., Chao, D. & Patel, H. Allogeneic hematopoietic stem-cell transplantation: the next generation of therapy for metastatic renal cell cancer. Nat Rev Clin Oncol 1, 32–38 (2004). https://doi.org/10.1038/ncponc0019

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncponc0019

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing