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Renal Cell Carcinoma

Nonmyeloablative stem cell transplantation in metastatic renal cell carcinoma: delayed graft-versus-tumor effect is associated with chimerism conversion but transplantation has high toxicity

Bone Marrow Transplantation volume 34, pages 309–316 (2004)Cite this article

Summary:

Seven out of 29 patients with metastatic renal cell carcinoma (RCC) considered eligible for allogeneic stem cell transplantation underwent nonmyeloablative stem cell transplantation (NST) from HLA-identical donors. Conditioning comprised cyclophosphamide, fludarabine and antithymocyte globulin. Prolonged mixed chimerism (MC) after engraftment converted to complete donor chimerism (CC) after infusion of donor lymphocytes and/or graft-versus-host disease (GvHD) in six patients. Five patients developed severe GvHD. Two of seven patients had a delayed tumor response after conversion to CC. After a median follow-up of 10 months (4–24 months), 5/7 patients are alive, one in very good partial remission (PR), one with stable and three with progressive disease. One of the seven patients died from sepsis in PR and 1/7 died from rapid tumor progression after sustained MC. None of the 22 nontransplanted patients responded to further therapies. Survival after 1 year was 59% in transplanted and 66% in nontransplanted patients (n.s.). A pooled data analysis from the literature suggests a graft-versus-tumor effect after transplant in patients with metastatic RCC, which becomes effective after chimerism conversion. Available data demonstrate high nonrelapse mortality in these patients. NST in RCC still has to be regarded as an investigational approach requiring careful patients' selection and longer follow-up within clinical studies.

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References

  1. Amato RJ . Chemotherapy for renal cell carcinoma. Semin Oncol 2000; 27: 177–186.

    CAS  PubMed  Google Scholar 

  2. Fairlamb DJ . 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 1981; 47: 2102–2106.

    Article  CAS  PubMed  Google Scholar 

  3. Figlin RA, Thompson JA, Bukowski RM et al. Multicenter, randomized, phase III trial of CD8(+) tumor-infiltrating lymphocytes in combination with recombinant interleukin-2 in metastatic renal cell carcinoma. J Clin Oncol 1999; 17: 2521–2529.

    Article  CAS  PubMed  Google Scholar 

  4. Chang AE, Li Q, Jiang G et al. Phase II trial of autologous tumor vaccination, anti-CD3-activated vaccine-primed lymphocytes, and interleukin-2 in stage IV renal cell cancer. J Clin Oncol 2003; 21: 884–890.

    Article  CAS  PubMed  Google Scholar 

  5. Atzpodien J, Kirchner H, Illiger HJ et al. IL-2 in combination with IFN-alpha and 5-FU versus tamoxifen in metastatic renal cell carcinoma: long-term results of a controlled randomized clinical trial. Br J Cancer 2001; 85: 1130–1136.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. 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 

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

    CAS  PubMed  Google Scholar 

  8. 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 

  9. 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.

    CAS  PubMed  Google Scholar 

  10. Slavin S, Nagler A, Naparstek E et al. Non-myeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and non malignant hematological diseases. Blood 1998; 91: 756–763.

    CAS  PubMed  Google Scholar 

  11. McSweeney PA, Niederwieser D, Shizuru JA et al. Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood 2001; 97: 3390–3400.

    Article  CAS  PubMed  Google Scholar 

  12. Massenkeil G, Nagy M, Lawang M et al. Reduced intensity conditioning and prophylactic DLI can cure patients with high-risk acute leukemias if complete donor chimerism can be achieved. Bone Marrow Transplant 2003; 31: 339–345.

    Article  CAS  PubMed  Google Scholar 

  13. 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 

  14. 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 

  15. 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 

  16. 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 

  17. Glucksberg H, Storb R, Fefer A et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HLA-matched sibling donors. Transplantation 1974; 18: 295–304.

    Article  CAS  PubMed  Google Scholar 

  18. Shulman HM, Sullivan KM, Weiden PL et al. Chronic graft-versus-host syndrome in man: a clinicopathological study of 20 long-term Seattle patients. Am J Med 1980; 69: 204–217.

    Article  CAS  PubMed  Google Scholar 

  19. Nagy M, Massenkeil G, Anders P et al. Short tandem repeat analysis to monitor chimerism after allogeneic stem cell transplantation. In: Sensabaugh GF, Lincoln PJ, Olaisen B (eds). Progress in Forensic Genetics, 8: Proceedings of the 18th International ISFH Congress. San Francisco, CA, 2000; pp 561–563.

    Google Scholar 

  20. Blin N, Stafford DW . A general method for isolation of high molecular weight DNA from eukaryotes. Nucleic Acids Res 1976; 3: 2303–2308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kaplan EL, Meier P . Nonparametric estimation for incomplete observations. J Am Stat Assoc 1958; 53: 457–481.

    Article  Google Scholar 

  22. Hinchey J, Chaves C, Appignani B et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996; 334: 494–500.

    Article  CAS  PubMed  Google Scholar 

  23. 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 

  24. 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 

  25. 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 

  26. Shlomchik WD, Couzens MS, Tang CB et al. Prevention of graft versus host disease by inactivation of host antigen-presenting cells. Science 1999; 285: 412–415.

    Article  CAS  PubMed  Google Scholar 

  27. Mapara MY, Kim YM, Wang SP et al. Donor lymphocyte infusions mediate superior graft-versus-leukemia effects in mixed compared to fully allogeneic chimeras: a critical role for host antigen-presenting cells. Blood 2002; 100: 1903–1909.

    Article  CAS  PubMed  Google Scholar 

  28. Orsini E, Alyea EP, Chillemi A et al. Conversion to full donor chimerism following donor lymphocyte infusion is associated with disease response in patients with multiple myeloma. Biol Blood Marrow Transplant 2000; 6: 375–386.

    Article  CAS  PubMed  Google Scholar 

  29. Mickisch GHJ, Garin A, van Pappel H et al. Radical nephrectomy plus interferon-alpha-based immunotherapy compared with interferon-alpha alone in metastatic renal-cell-carcinoma: a randomised trial. Lancet 2001; 358: 966–970.

    Article  CAS  PubMed  Google Scholar 

  30. Storb RF, Lucarelli G, McSweeney PA, Childs RW . Hematopoietic cell transplantation for benign hematological disorders and solid tumors. Hematology (Am Soc Hematol Educ Program) 2003, 372–397.

    Article  Google Scholar 

  31. Gijtenbeek JMM, van den Bent MJ, Vecht CH J . Cyclosporine neurotoxicity: a review. J Neurol 1999; 246: 339–346.

    Article  CAS  PubMed  Google Scholar 

  32. Sullivan KM, Agura E, Anasetti C et al. Chronic graft-versus-host disease and other late complications of bone marrow transplantation. Semin Hematol 1991; 28: 250–259.

    CAS  PubMed  Google Scholar 

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Author notes

  1. G Massenkeil and J Roigas: Contributed equally to this work

Authors and Affiliations

  1. Department of Hematology and Oncology, Campus Virchow-Klinikum, University Hospital Charité, Berlin, Germany

    G Massenkeil, M Y Mapara, B Dörken & R Arnold

  2. Clinic of Urology, Campus Virchow-Klinikum, University Hospital Charité, Berlin, Germany

    J Roigas, A Wille & S Loening

  3. Institute of Legal Medicine, Campus Virchow-Klinikum, University Hospital Charité, Berlin, Germany

    M Nagy

  4. Department of Radiology, Campus Virchow-Klinikum, University Hospital Charité, Berlin, Germany

    C Stroszczynski

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Correspondence to G Massenkeil.

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Massenkeil, G., Roigas, J., Nagy, M. et al. Nonmyeloablative stem cell transplantation in metastatic renal cell carcinoma: delayed graft-versus-tumor effect is associated with chimerism conversion but transplantation has high toxicity. Bone Marrow Transplant 34, 309–316 (2004). https://doi.org/10.1038/sj.bmt.1704587

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