Skip to main content

Advertisement

SpringerLink
Log in

Regression of advanced melanoma upon withdrawal of immunosuppression: case series and literature review

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

We report two cases of stage IV malignant melanoma arising in patients treated with azathioprine for myasthenia gravis. In both cases, the melanoma metastases regressed upon withdrawal of immunosuppression. One patient remains melanoma free at 10 years, and the second patient experienced an 18-month disease free period. There is one prior case report in the medical literature to support full immune reconstitution for treatment in advanced immunosuppression-related melanoma, and one case series suggesting that transplant patients developing melanoma may benefit from a switch to sirolimus. Virtually, no data exist for the medical management of early stage melanoma in the immunosuppressed patients. We review the limited preclinical data in support of immune reconstitution and the data on immunosuppression as a risk factor for melanoma. We conclude that reduction or withdrawal of immunosuppression may be beneficial in patients with advanced stage melanoma and warrants further consideration in patients with early stage melanoma.

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.

Similar content being viewed by others

References

  1. Penn I, Hammond W, Brettschneider L, Starzl TE. Malignant lymphomas in transplantation patients. Transpl Proc. 1969;1(1):106–12.

    CAS  Google Scholar 

  2. Le Mire L, Hollowood K, Gray D, Bordea C, Wojnarowska F. Melanomas in renal transplant recipients. Br J Dermatol. 2006;154(3):472–7.

    Article  PubMed  Google Scholar 

  3. Sheil AG. Cancer after transplantation. World J Surg. 1986;10:389–96.

    Article  CAS  PubMed  Google Scholar 

  4. Kasiske BL, Snyder JJ, Gilbertson DT, Wang C. Cancer after kidney transplantation in the United States. Am J Transplant. 2004;4(6):905–13.

    Article  PubMed  Google Scholar 

  5. Arichi N, Kishikawa H, Nishimura K, et al. Malignancy following kidney transplantation. Transplant Proc. 2008;40(7):2400–2.

    Article  CAS  PubMed  Google Scholar 

  6. Randle HW. The historical link between solid-organ transplantation, immunosuppression, and skin cancer. Dermatol Surg. 2004;30:595–7.

    Article  PubMed  Google Scholar 

  7. Berg D, Otley CC. Skin cancer in organ transplant recipients: epidemiology, pathogenesis, and management. J Am Acad Dermatol. 2002;47:1–17.

    Article  PubMed  Google Scholar 

  8. Barker JN, MacDonald DM. Eruptive naevi following renal transplantation. Clin Exp Dermatol. 1988;13:123–5.

    Article  CAS  PubMed  Google Scholar 

  9. Greene MH, Young TI, Clark WH Jr. Malignant melanoma in renal-transplant recipients. Lancet. 1981;1(8231):1196–9.

    Article  CAS  PubMed  Google Scholar 

  10. Sheil AG, Flavel S, Disney AP, et al. Cancer development in patients progressing to dialysis and renal transplantation. Transplant Proc. 1985;17:1685–8.

    CAS  PubMed  Google Scholar 

  11. Dinh Q, Chong A. Melanoma in organ transplant recipients: the old enemy finds a new battleground. Aust J Dermatol. 2007;48:199–207.

    Article  Google Scholar 

  12. Chapman J, Webster AC. Cancer report: ANZDATA Registry 2004 report, 2004:99.

  13. Bouwes Bavinck JN, Hardie DR, Green A, et al. The risk of skin cancer in renal transplant recipients in Queensland, Australia. A follow-up study. Transplantation. 1996;61(5):715–21.

    Article  CAS  PubMed  Google Scholar 

  14. Lindelof B, Sigurgeirsson B, Gabel H, Stern RS. Incidence of skin cancer in 5356 patients following organ transplantation. Br J Dermatol. 2000;143:513–9.

    CAS  PubMed  Google Scholar 

  15. Hasegawa W, Pond GR, Rifkind JT, et al. Long-term follow-up of secondary malignancies in adults after allogeneic bone marrow transplantation. Bone Marrow Transplant. 2005;35:51–5.

    Article  CAS  PubMed  Google Scholar 

  16. Lishner M, et al. Cutaneous and mucosal neoplasms in bone marrow transplant recipients. Cancer. 1990;65(3):473–6.

    Article  CAS  PubMed  Google Scholar 

  17. Curtis RE, Rowlings PA, Deeg HJ, Shriner DA, Socie G, Travis LB, et al. Solid cancers after bone marrow transplantation. N Engl J Med. 1997;336:897–904.

    Article  CAS  PubMed  Google Scholar 

  18. Socie G, et al. New malignant diseases after allogeneic marrow transplantation for childhood acute leukemia. J Clin Oncol. 2000;18:348–57.

    CAS  PubMed  Google Scholar 

  19. Deeg HJ, et al. Malignancies after marrow transplantation for aplastic anemia and fanconi anemia: a joint Seattle and Paris analysis of results in 700 patients. Blood. 1996;87:386–92.

    CAS  PubMed  Google Scholar 

  20. Ferry C, Gemayel G, Rocha V, et al. Long-term outcomes after allogeneic stem cell transplantation for children with hematological malignancies. Bone Marrow Transplant. 2007;40(3):219–24.

    Article  CAS  PubMed  Google Scholar 

  21. Rizzo JD, Curtis RE, Socié G, et al. Solid cancers after allogeneic hematopoietic cell transplantation. Blood. 2009;113(5):1175–83.

    Article  CAS  PubMed  Google Scholar 

  22. Bhatia S, Ramsay NK, Steinbuch M, et al. Malignant neoplasms following bone marrow transplantation. Blood. 1996;87(9):3633–9.

    CAS  PubMed  Google Scholar 

  23. Cibere J, Sibley J, Haga M. Rheumatoid arthritis and the risk of malignancy. Arthritis Rheum. 1997;40:1580–6.

    Article  CAS  PubMed  Google Scholar 

  24. Clair EW, van der Heijde DM, Smolen JS, et al. Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial. Arthritis Rheum. 2004;50(11):3432–43.

    Article  Google Scholar 

  25. Bongartz T, et al. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA. 2006;295(19):2275–85.

    Article  CAS  PubMed  Google Scholar 

  26. Buchbinder R, Barber M, Heuzenroeder L, et al. Incidence of melanoma and other malignancies among rheumatoid arthritis patients treated with methotrexate. Arthritis Rheum. 2008;59(6):794–9.

    Article  CAS  PubMed  Google Scholar 

  27. Van den Borne BE, Landewe RB, Houkes I, et al. No increased risk of malignancies and mortality in cyclosporin A-treated patients with rheumatoid arthritis. Arthritis Rheum. 1998;41(11):1930–7.

    Article  PubMed  Google Scholar 

  28. Isomäki H, Hakulinen T, Joutsenlahti U. Excess risk of lymphomas, leukemia and myeloma in patients with rheumatoid arthritis. J Chronic Dis. 1978;31:691–6.

    Article  PubMed  Google Scholar 

  29. Wolfe F, Michaud K. The association of new cases of cancer with biologic therapy [abstract]. Arthritis Rheum. 2006;Suppl 54:S549.

    Google Scholar 

  30. Kwon JH, Farrell RJ. The risk of lymphoma in the treatment of inflammatory bowel disease with immunosuppressive agents. Crit Rev Oncol Hematol. 2005;56(1):169–78.

    Article  PubMed  Google Scholar 

  31. Stone JH, Holbrook JT, Marriott MA, et al. Solid malignancies among patients in the Wegener’s Granulomatosis Etanercept Trial. Arthritis Rheum. 2006;54(5):1608–18.

    Article  CAS  PubMed  Google Scholar 

  32. Kakrida M, Orengo I, Markus R. Sudden onset of multiple nevi after administration of 6-mercaptopurine in an adult with Crohn’s disease: a case report. Int J Dermatol. 2005;44(4):334–6.

    Article  PubMed  Google Scholar 

  33. Levin N, Abramsky O, Lossos A, et al. Extrathymic malignancies in patients with myasthenia gravis. J Neurol Sci. 2005;237(1–2):39–43.

    Article  PubMed  Google Scholar 

  34. Frisch M, Biggar RJ, Engels EA, Goedert JJ. Association of cancer with AIDS-related immunosuppression in adults. JAMA. 2001;285:1736–45.

    Article  CAS  PubMed  Google Scholar 

  35. Pantanowitz L, Schlecht HP, Dezube BJ. The growing problem of non-AIDS-defining malignancies in HIV. Curr Opin Oncol. 2006;18:469–78.

    Article  PubMed  Google Scholar 

  36. Grulich AE, van Leeuwen MT, Falster MO, Vajdic CM. Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet. 2007;370:59–67.

    Article  PubMed  Google Scholar 

  37. Oble DA, Loewe R, Yu P, Mihm MC. Focus on TILs: prognostic significance of tumor infiltrating lymphocytes in human melanoma. Cancer Immun. 2009;9:3.

    PubMed  Google Scholar 

  38. Hartmann A, Bedenk C, Keikavoussi P, Becker JC, Hamm H, Brocker EB. Vitiligo and melanoma-associated hypopigmentation (MAH): shared and discriminative features. J Dtsch Dermatol Ges. 2008;6(12):1053–9.

    Article  PubMed  Google Scholar 

  39. Kalialis LV, Drzewiecki KT, Mohammadi M, Mehlsen AB, Klyver H. Spontaneous regression of metastases from malignant melanoma: a case report. Melanoma Res. 2008;18(4):279–83.

    Article  PubMed  Google Scholar 

  40. Sumner WC, Foraker AG. Spontaneous regression of human melanoma: clinical and experimental studies. Cancer. 1960;13:79–81.

    Article  CAS  PubMed  Google Scholar 

  41. Stidolph NE. Malignant melanoma: regression of metastases after excision of primary growth. Proc R Soc Med. 1967;60(1):1.

    CAS  PubMed  Google Scholar 

  42. Jensen OA, Andersen SR. Spontaneous regression of a malignant melanoma of the choroid. Acta Ophthalmol. 1974;52(2):173–82.

    CAS  Google Scholar 

  43. Kirkwood JM, Strawderman MH, Ernstoff MS, Smith TJ, Borden EC, Blum RH. Interferon alfa-2b adjuvant therapy of high risk resected cutaneous melanoma: the Eastern Cooperative Oncology Trial EST 1684. J Clin Oncol 1996;14(1):7–17.

    CAS  PubMed  Google Scholar 

  44. Gogas H, Ioannovich IJ, Dafni U, Stavropoulou-Giokas C, Frangia K, Tsoutsos D, Panagiotou P, Polyzos A, Papadopoulos O, Stratigos A, Markopoulos C, Bafaloukos D, Pectasides D, Fountzilas G, Kirkwood JM. Prognostic significance of autoimmunity during treatment of melanoma with interferon. N Engl J Med 2006;354(7):758-60.

    Article  Google Scholar 

  45. Atkins MD, Lotze MT, Dutcher JP, et al. High-dose recombinant interleukin-2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol 1999;17:2105–16.

    CAS  PubMed  Google Scholar 

  46. Dudley ME, Wunderlich JR, Robbins PF, et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science. 2002;298(5594):850–4.

    Article  CAS  PubMed  Google Scholar 

  47. Hunder NN, Wallen H, Cao J, et al. Treatment of metastatic melanoma with autologous CD4+ T cells against NY-ESO-1. N Engl J Med. 2008;358(25):2698–703.

    Article  CAS  PubMed  Google Scholar 

  48. Riley LB, Agarwala SS. Melanoma vaccines. Expert Rev Vaccines. 2008;7(7):937–49.

    Article  CAS  PubMed  Google Scholar 

  49. Yang W, Chen PW, Li H, Alizadeh H, Niederkorn JY. PD-L1: PD-1 interaction contributes to the functional suppression of T-cell responses to human uveal melanoma cells in vitro. Invest Ophthalmol Vis Sci. 2008;49(6):2518–25.

    Article  PubMed  Google Scholar 

  50. Hodi FS, Granter S, Antin J. Withdrawal of immunosuppression contributing to the remission of malignant melanoma: a case report. Cancer Immun. 2005;5:7.

    PubMed  Google Scholar 

  51. Boratynska M, Watorek E, Smolska D, Patrzalek D, Klinger M. Anticancer effect of sirolimus in renal allograft recipients with de novo malignancies. Transpl Proc. 2007;39(9):2736–9.

    Article  CAS  Google Scholar 

  52. Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 2002;3:991–8.

    Article  CAS  PubMed  Google Scholar 

  53. Zattra E, Fortina AB, Bordignon M, Piaserico S, Alaibac M. Immunosuppression and melanocyte proliferation. Melanoma Res. 2009;19(2):63–8.

    Article  PubMed  Google Scholar 

  54. Boivin JF, O’Brien K. Solid cancer risk after treatment of Hodgkin’s disease. Cancer. 1988;61(12):2541–6.

    Article  CAS  PubMed  Google Scholar 

  55. Swerdlow AJ, Barber JA, Horwich A, Cunningham D, Milan S, Omar RZ. Second malignancy in patients with Hodgkin’s disease treated at the Royal Marsden Hospital. Br J Cancer. 1997;75(1):116–23.

    CAS  PubMed  Google Scholar 

  56. Radis CD, Kahl LE, Baker GL, et al. Effects of cyclophosphamide on the development of malignancy and on long-term survival of patients with rheumatoid arthritis. A 20-year followup study. Arthritis Rheum. 1995;38(8):1120–7.

    Article  CAS  PubMed  Google Scholar 

  57. Frezza EE, Fung JJ, van Thiel DH. Non-lymphoid cancer after liver transplantation. Hepatogastroenterology. 1997;44(16):1172–81.

    CAS  PubMed  Google Scholar 

  58. Guenova E, Lichte V, Hoetzenecker W, et al. Nodular malignant melanoma and multiple cutaneous neoplasms under immunosuppression with azathioprine. Melanoma Res. 2009;19(4):271–3.

    Article  PubMed  Google Scholar 

  59. Reutter JC, Long EM, Morrell DS, Thomas NE, Groben PA. Eruptive post-chemotherapy in situ melanomas and dysplastic nevi. Pediatr Dermatol. 2007;24(2):135–7.

    Article  PubMed  Google Scholar 

  60. Potter T, Hardwick N, Mulherin D. Multiple malignant melanomas in a patient with RA treated with methotrexate. J Rheumatol. 1998;25(11):2282–3.

    CAS  PubMed  Google Scholar 

  61. Jeannou J, Goupille P, Valat JP. Association of methotrexate, rheumatoid arthritis, and melanoma in 2 patients. J Rheumatol. 1997;24(7):1444–5.

    CAS  PubMed  Google Scholar 

  62. Barnhill RL, Wiles JC. Malignant melanoma associated with multiple therapies for psoriasis. J Am Acad Dermatol. 1989;21(1):148–50.

    Article  CAS  PubMed  Google Scholar 

  63. Webster AC, Playford EG, Higgins G, Chapman JR, Craig JC. Interleukin 2 receptor antagonists for renal transplant recipients: a meta-analysis of randomized trials. Transplantation. 2004;77(2):166–76.

    Article  CAS  PubMed  Google Scholar 

  64. Dreyer L, Mellemkjaer L, Hetland ML. Cancer in arthritis patients after anti-tumour necrosis factor therapy. Ugeskr Laeger. 2009;171(7):506–11.

    PubMed  Google Scholar 

  65. Khan I, Rahman L, McKenna DB. Primary cutaneous melanoma: a complication of infliximab treatment? Clin Exp Dermatol. 2009;34(4):524–6.

    Article  CAS  PubMed  Google Scholar 

  66. Fulchiero GJ Jr, Salvaggio H, Drabick JJ, et al. Eruptive latent metastatic melanomas after initiation of antitumor necrosis factor therapies. J Am Acad Dermatol. 2007;56(5 Suppl):S65–7.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 130 Manning Dr, CB 7305, Chapel Hill, NC, 27516, USA

    P. Dillon, N. Sharpless & F. Collichio

  2. Department of Dermatology, The University of North Carolina at Chapel Hill, 130 Manning Dr, CB 7305, Chapel Hill, NC, 27516, USA

    N. Thomas

Authors
  1. P. Dillon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N. Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N. Sharpless
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. F. Collichio
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P. Dillon.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dillon, P., Thomas, N., Sharpless, N. et al. Regression of advanced melanoma upon withdrawal of immunosuppression: case series and literature review. Med Oncol 27, 1127–1132 (2010). https://doi.org/10.1007/s12032-009-9348-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12032-009-9348-z

Keywords

Search

Navigation