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.

  • Original Article
  • Published:

Allografting

Long-term follow-up of nonmyeloablative allogeneic stem cell transplantation for renal cell carcinoma: The University of Chicago Experience

Bone Marrow Transplantation volume 35, pages 253–260 (2005)Cite this article

Summary:

Nonmyeloablative allogeneic stem cell transplantation (NST) has considerable activity in patients with metastatic renal cell carcinoma (RCC), although there are limited long-term follow-up data. Between February 1999 and May 2003, 18 patients with metastatic RCC underwent 19 matched-sibling NSTs after conditioning with fludarabine and cyclophosphamide with tacrolimus and mycophenolate mofetil as post-transplant immunosuppression. Among the four objective responses, all were partial and have relapsed with a median response duration of 609 days (range, 107–926). All responders are alive at a median of 41 months. Median overall survival for the entire cohort was 14 months. There were four early treatment-related deaths and one late treatment-related death. Eight patients died from progressive disease and five (28%) from treatment-related mortality. Stratifying transplant outcome as early death, intermediate (no response, no early death), or response, the combination of pre-treatment anemia and decreased performance status, was associated with adverse outcome (P=0.015) and reduced survival (HR 5.4, 95% confidence interval of 1.4 to 21, P=0.007). Responders demonstrated prolonged survival compared to nonresponders (P=0.002). NST leads to durable responses in a minority of metastatic RCC patients. Appropriate patient selection is paramount. Anemia and decreased performance status may enable risk stratification.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1

Similar content being viewed by others

References

  1. Fyfe G, Fisher RI, Rosenberg SA et al. Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol 1995; 13: 688–696.

    Article  CAS  PubMed  Google Scholar 

  2. Motzer RJ, Bacik J, Murphy BA et al. Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol 2002; 20: 289–296.

    Article  CAS  PubMed  Google Scholar 

  3. Motzer RJ, Russo P . Systemic therapy for renal cell carcinoma. J Urol 2000; 163: 408–417.

    Article  CAS  PubMed  Google Scholar 

  4. Caignard A, Guillard M, Gaudin C et al. In situ demonstration of renal-cell-carcinoma-specific T-cell clones. Int J Cancer 1996; 66: 564–570.

    Article  CAS  PubMed  Google Scholar 

  5. Weiden PL, Sullivan KM, Flournoy N et al. Antileukemic effect of chronic graft-versus-host disease: contribution to improved survival after allogeneic marrow transplantation. N Engl J Med 1981; 304: 1529–1533.

    Article  CAS  PubMed  Google Scholar 

  6. Weiden PL, Storb R, Deeg HJ et al. Prolonged disease-free survival in dogs with lymphoma after total-body irradiation and autologous marrow transplantation consolidation of combination-chemotherapy-induced remissions. Blood 1979; 54: 1039–1049.

    CAS  PubMed  Google Scholar 

  7. 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.

    CAS  PubMed  Google Scholar 

  8. 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  CAS  PubMed  Google Scholar 

  9. Ueno NT, Cheng YC, Rondon G et al. Rapid induction of complete donor chimerism by the use of a reduced-intensity conditioning regimen composed of fludarabine and melphalan in allogeneic stem-cell transplantation for metastatic solid tumors. Blood 2003; 102: 3829–3836.

    Article  CAS  PubMed  Google Scholar 

  10. Rini BI, Zimmerman T, Stadler WM et al. Allogeneic stem-cell transplantation of renal cell cancer after nonmyeloablative chemotherapy: feasibility, engraftment, and clinical results. J Clin Oncol 2002; 20: 2017–2024.

    Article  PubMed  Google Scholar 

  11. Pedrazzoli P, Da Prada GA, Giorgiani G et al. Allogeneic blood stem cell transplantation after a reduced-intensity, preparative regimen: a pilot study in patients with refractory malignancies. Cancer 2002; 94: 2409–2415.

    Article  PubMed  Google Scholar 

  12. Hentschke P, Barkholt L, Uzunel M et al. Low-intensity conditioning and hematopoietic stem cell transplantation in patients with renal and colon carcinoma. Bone Marrow Transplant 2003; 31: 253–261.

    Article  CAS  PubMed  Google Scholar 

  13. Baron F, Frere P, Baudoux E et al. Non-myeloablative stem cell transplantation with low-dose total body irradiation and fludarabine for metastatic renal cell carcinoma. Haematologica 2003; 88: 479–480.

    Google Scholar 

  14. Blaise D, Bay JO, Faucher C et al. Reduced-intensity preparative regimen and allogeneic stem cell transplantation for advanced solid tumors. Blood 2004; 103: 435–441.

    Article  CAS  PubMed  Google Scholar 

  15. Motzer RJ, Mazumdar M, Bacik J et al. Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol 1999; 17: 2530–2540.

    Article  CAS  PubMed  Google Scholar 

  16. Motzer RJ, Bacik J, Schwartz LH et al. Prognostic factors for survival in previously treated patients with metastatic renal cell carcinoma. J Clin Oncol 2004; 22: 454–463.

    Article  PubMed  Google Scholar 

  17. Citterio G, Bertuzzi A, Tresoldi M et al. Prognostic factors for survival in metastatic renal cell carcinoma: retrospective analysis from 109 consecutive patients. Eur Urol 1997; 31: 286–291.

    Article  CAS  PubMed  Google Scholar 

  18. Mejean A, Hopirtean V, Bazin JP et al. Prognostic factors for the survival of patients with papillary renal cell carcinoma: meaning of histological typing and multifocality. J Urol 2003; 170: 764–767.

    Article  PubMed  Google Scholar 

  19. Naito S, Kimiya K, Sakamoto N et al. Prognostic factors and value of adjunctive nephrectomy in patients with stage IV renal cell carcinoma. Urology 1991; 37: 95–99.

    Article  CAS  PubMed  Google Scholar 

  20. Ljungberg B, Landberg G, Alamdari FI . Factors of importance for prediction of survival in patients with metastatic renal cell carcinoma, treated with or without nephrectomy. Scand J Urol Nephrol 2000; 34: 246–251.

    Article  CAS  PubMed  Google Scholar 

  21. Van Besien K, Devine S, Wickrema A et al. Regimen-related toxicity after fludarabine–melphalan conditioning: a prospective study of 31 patients with hematologic malignancies. Bone Marrow Transplant 2003; 32: 471–476.

    Article  CAS  PubMed  Google Scholar 

  22. Stata Statistical Software [computer program]. Version 8.0. Stata Corporation: College Station, TX, 2003.

  23. Stevens MF, Hickman JA, Stone R et al. Antitumor imidazotetrazines. 1. Synthesis and chemistry of 8-carbamoyl-3-(2-chloroethyl)imidazo[5,1-d]-1,2,3,5-tetrazin-4(3 H)-one, a novel broad-spectrum antitumor agent. J Med Chem 1984; 27: 196–201.

    Article  CAS  PubMed  Google Scholar 

  24. Lee DS, White DE, Hurst R et al. Patterns of relapse and response to retreatment in patients with metastatic melanoma or renal cell carcinoma who responded to interleukin-2-based immunotherapy. Cancer J Sci Am 1998; 4: 86–93.

    CAS  PubMed  Google Scholar 

  25. Escudier B, Chevreau C, Lasset C et al. Cytokines in metastatic renal cell carcinoma: is it useful to switch to interleukin-2 or interferon after failure of a first treatment? Groupe Francais d’Immunotherape. J Clin Oncol 1999; 17: 2039–2043.

    Article  CAS  PubMed  Google Scholar 

  26. Childs R, Clave E, Contentin N et al. Engraftment kinetics after nonmyeloablative allogeneic peripheral blood stem cell transplantation: full donor T-cell chimerism precedes alloimmune responses. Blood 1999; 94: 3234–3241.

    CAS  PubMed  Google Scholar 

  27. Gratwohl A, Brand R, Apperley J et al. Graft-versus-host disease and outcome in HLA-identical sibling transplantations for chronic myeloid leukemia. Blood 2002; 100: 3877–3886.

    Article  CAS  PubMed  Google Scholar 

  28. Appelbaum FR, Sandmaier B . Sensitivity of renal cell cancer to nonmyeloablative allogeneic hematopoietic cell transplantations: unusual or unusually important? J Clin Oncol 2002; 20: 1965–1967.

    Article  PubMed  Google Scholar 

  29. Frost P, Caliliw R, Belldegrun A, Bonavida B . Immunosensitization of resistant human tumor cells to cytotoxicity by tumor infiltrating lymphocytes. Int J Oncol 2003; 22: 431–437.

    PubMed  Google Scholar 

  30. Bregni M, Dodero A, Peccatori J et al. Nonmyeloablative conditioning followed by hematopoietic cell allografting and donor lymphocyte infusions for patients with metastatic renal and breast cancer. Blood 2002; 99: 4234–4236.

    Article  CAS  PubMed  Google Scholar 

  31. Childs R, Srinivasan R . Advances in allogeneic stem cell transplantation: directing graft-versus-leukemia at solid tumors. Cancer J 2002; 8: 2–11.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Chicago Hospitals, Chicago, IL, USA

    A S Artz, K Van Besien, T Zimmerman, T F Gajewski, W M Stadler & N J Vogelzang

  2. The University of California San Francisco, San Francisco, CA, USA

    B I Rini

  3. St John Mercy Medical Center, St Louis, IL, USA

    H S Hu

Authors
  1. A S Artz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K Van Besien
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T Zimmerman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T F Gajewski
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. B I Rini
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. H S Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. W M Stadler
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. N J Vogelzang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A S Artz.

Additional information

Prior Presentation or Publication

1. Proceedings of the American Society of Clinical Oncology, 2001.

2. Proceedings of the American Society of Clinical Oncology, 2002.

3. Tandem Bone Marrow Transplant Meeting, 2004.

4. The initial report was in J Clin Oncol 2002; 20: 2017–2024.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Artz, A., Van Besien, K., Zimmerman, T. et al. Long-term follow-up of nonmyeloablative allogeneic stem cell transplantation for renal cell carcinoma: The University of Chicago Experience. Bone Marrow Transplant 35, 253–260 (2005). https://doi.org/10.1038/sj.bmt.1704760

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1704760

Keywords

This article is cited by

Search

Advanced search

Quick links