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Post-Transplant Events

Skin cancer after nonmyeloablative hematopoietic cell transplantation

Bone Marrow Transplantation volume 37, pages 1103–1108 (2006)Cite this article

Abstract

Squamous cell carcinoma (SCC) is the most common skin cancer in patients receiving immunosuppressive therapy, and is well documented to occur in patients that have undergone either solid organ transplantation or conventional myeloablative bone marrow transplantation. Nonmyeloablative hematopoietic cell transplantation (NMAT) provides transient, intensive immunosuppression, permitting allogeneic engraftment without ablating the marrow. The purpose of this report is to describe six patients that developed SCC (n=3), basal cell carcinoma (n=2), or malignant melanoma (n=2) over a period of 2–26 months following NMAT. All patients had myelodysplasia or acute myelogenous leukemia prior to transplantation. The authors demonstrate for the first time that patients who undergo NMAT are at risk for developing skin cancers and emphasize the need for close surveillance in the post transplantation period.

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References

  1. Landis SH, Murray T, Bolden S, Wingo PA . Cancer statistics, 1999. CA Cancer J Clin 1999; 49: 8–31.

    Article  CAS  PubMed  Google Scholar 

  2. Rhodes AR . Public education and cancer of the skin. What do people need to know about melanoma and nonmelanoma skin cancer? Cancer 1995; 75: 613–636.

    Article  CAS  PubMed  Google Scholar 

  3. Marks R . An overview of skin cancers. Incidence and causation. Cancer 1995; 75: 607–612.

    Article  CAS  PubMed  Google Scholar 

  4. 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 

  5. Walder BK, Robertson MR, Jeremy D . Skin cancer and immunosuppression. Lancet 1971; 2: 1282–1283.

    Article  CAS  PubMed  Google Scholar 

  6. Kanitakis J, Alhaj-Ibrahim L, Euvrard S, Claudy A . Basal cell carcinomas developing in solid organ transplant recipients: clinicopathologic study of 176 cases. Arch Dermatol 2003; 139: 1133–1137.

    Article  PubMed  Google Scholar 

  7. Ramsay HM, Fryer AA, Hawley CM, Smith AG, Harden PN . Non-melanoma skin cancer risk in the Queensland renal transplant population. Br J Dermatol 2002; 147: 950–956.

    Article  CAS  PubMed  Google Scholar 

  8. Ramsay HM, Fryer AA, Hawley CM, Smith AG, Nicol DL, Harden PN . Factors associated with nonmelanoma skin cancer following renal transplantation in Queensland, Australia. J Am Acad Dermatol 2003; 49: 397–406.

    Article  PubMed  Google Scholar 

  9. Lindelof B, Sigurgeirsson B, Gabel H, Stern RS . Incidence of skin cancer in 5356 patients following organ transplantation. Br J Dermatol 2000; 143: 513–519.

    CAS  PubMed  Google Scholar 

  10. Hasegawa W, Pond GR, Rifkind JT, Messner HA, Lau A, Daly AS et al. Long-term follow-up of secondary malignancies in adults after allogeneic bone marrow transplantation. Bone Marrow Transplant 2005; 35: 51–55.

    Article  CAS  PubMed  Google Scholar 

  11. Lishner M, Patterson B, Kandel R, Fyles G, Curtis JE, Meharchand J et al. Cutaneous and mucosal neoplasms in bone marrow transplant recipients. Cancer 1990; 65: 473–476.

    Article  CAS  PubMed  Google Scholar 

  12. Gmeinhart B, Hinterberger W, Greinix HT, Rabitsch W, Kirnbauer R, Reiter E et al. Anaplastic squamous cell carcinoma (SCC) in a patient with chronic cutaneous graft-versus-host disease (GVHD). Bone Marrow Transplant 1999; 23: 1197–1199.

    Article  CAS  PubMed  Google Scholar 

  13. 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 

  14. Curtis RE, Metayer C, Rizzo JD, Socie G, Sobocinski KA, Flowers ME et al. Impact of chronic GVHD therapy on the development of squamous cell cancers after hematopoietic stem-cell transplantation: an international case-control study. Blood 2005; 105: 3802–3811.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Bhatia S, Ramsay NK, Steinbuch M, Dusenbery KE, Shapiro RS, Weisdorf DJ et al. Malignant neoplasms following bone marrow transplantation. Blood 1996; 87: 3633–3639.

    CAS  PubMed  Google Scholar 

  16. Giralt S, Estey E, Albitar M, van Besien K, Rondon G, Anderlini P 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 

  17. Khouri IF, Keating M, Korbling M, Przepiorka D, Anderlini P, O’Brien S et al. Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies. J Clin Oncol 1998; 16: 2817–2824.

    Article  CAS  PubMed  Google Scholar 

  18. Slavin S, Nagler A, Naparstek E, Kapelushnik Y, Aker M, Cividalli G 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.

    CAS  PubMed  Google Scholar 

  19. Childs R, Clave E, Contentin N, Jayasekera D, Hensel N, Leitmen S 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 

  20. Storb R, Yu C, Sandmaier BM, McSweeney PA, Georges G, Nash RA et al. Mixed hematopoietic chimerism after marrow allografts. Transplantation in the ambulatory care setting. Ann NY Acad Sci 1999; 872: 372–376.

    Article  CAS  PubMed  Google Scholar 

  21. Grigg A, Seymour JF, Roberts A, Szer J . Mini-allografts’ for haematological malignancies: an alternative to conventional myeloablative marrow transplantation. Aust NZ J Med 1999; 29: 308–314.

    Article  CAS  Google Scholar 

  22. Champlin R, Khouri I, Shimoni A, Gajewski J, Kornblau S, Molldrem J et al. Harnessing graft-versus-malignancy: non-myeloablative preparative regimens for allogeneic haematopoietic transplantation, an evolving strategy for adoptive immunotherapy. Br J Haematol 2000; 111: 18–29.

    Article  CAS  PubMed  Google Scholar 

  23. Sakiyama M, Kami M, Hori A, Imataki O, Hamaki T, Murashige N et al. Regimen-related toxicity following reduced-intensity stem-cell transplantation (RIST): comparison between Seattle criteria and National Cancer Center Common Toxicity Criteria (NCI-CTC) version 2.0. Bone Marrow Transplant 2004; 34: 787–794.

    Article  CAS  PubMed  Google Scholar 

  24. Sullivan KM . Acute and chronic graft-versus-host disease in man. Int J Cell Cloning 1986; 4: 42–93.

    Article  PubMed  Google Scholar 

  25. Socie G . Chronic graft-versus-host disease: clinical features and grading systems. Int J Hematol 2004; 79: 216–220.

    Article  PubMed  Google Scholar 

  26. Hurley CK, Baxter Lowe LA, Logan B, Karanes C, Anasetti C, Weisdorf D et al. National Marrow Donor Program HLA-matching guidelines for unrelated marrow transplants. Biol Blood Marrow Transplant 2003; 9: 610–615.

    Article  PubMed  Google Scholar 

  27. Nelson Jr RP, Robertson MJ, Cripe LD, Hromas R, Schwartz JE, Yu M et al. Outcomes after matched related and unrelated nonmyeloablative allotransplantation for advanced hematological malignancies. Am J Hematol 2006, submitted.

  28. Martinez JC, Otley CC, Stasko T, Euvrard S, Brown C, Schanbacher CF et al. Defining the clinical course of metastatic skin cancer in organ transplant recipients: a multicenter collaborative study. Arch Dermatol 2003; 139: 301–306.

    Article  PubMed  Google Scholar 

  29. Randle HW . The historical link between solid-organ transplantation, immunosuppression, and skin cancer. Dermatol Surg 2004; 30: 595–597.

    PubMed  Google Scholar 

  30. Jensen P, Hansen S, Moller B, Leivestad T, Pfeffer P, Fauchald P et al. Are renal transplant recipients on CsA-based immunosuppressive regimens more likely to develop skin cancer than those on azathioprine and prednisolone? Transplant Proc 1999; 31: 1120.

    Article  CAS  PubMed  Google Scholar 

  31. Jensen P, Hansen S, Moller B, Leivestad T, Pfeffer P, Geiran O et al. Skin cancer in kidney and heart transplant recipients and different long-term immunosuppressive therapy regimens. J Am Acad Dermatol 1999; 40 (2 Part 1): 177–186.

    Article  CAS  PubMed  Google Scholar 

  32. Otley CC, Pittelkow MR . Skin cancer in liver transplant recipients. Liver Transplant 2000; 6: 253–262.

    Article  CAS  Google Scholar 

  33. Lober BA, Lober CW, Accola J . Actinic keratosis is squamous cell carcinoma. J Am Acad Dermatol 2000; 43: 881–882.

    Article  CAS  PubMed  Google Scholar 

  34. Szeto CH, Shek TW, Lie AK, Au WY, Yuen AP, Kwong YL . Squamous cell carcinoma of the tongue complicating chronic oral mucosal graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Am J Hematol 2004; 77: 200–202.

    Article  PubMed  Google Scholar 

  35. Fortina AB, Piaserico S, Zattra E, Alaibac M . Dermoscopic features of eruptive melanocytic naevi in an adult patient receiving immunosuppressive therapy for Crohn’s disease. Melanoma Res 2005; 15: 223–224.

    Article  Google Scholar 

  36. Austin AS, Spiller RC . Inflammatory bowel disease, azathioprine and skin cancer: case report and literature review. Eur J Gastroenterol Hepatol 2001; 13: 193–194.

    Article  CAS  PubMed  Google Scholar 

  37. Chun HG, Leyland-Jones B, Cheson BD . Fludarabine phosphate: a synthetic purine antimetabolite with significant activity against lymphoid malignancies. J Clin Oncol 1991; 9: 175–188.

    Article  CAS  PubMed  Google Scholar 

  38. Goodman ER, Fiedor PS, Fein S, Athan E, Hardy MA . Fludarabine phosphate: a DNA synthesis inhibitor with potent immunosuppressive activity and minimal clinical toxicity. Am Surg 1996; 62: 435–442.

    CAS  PubMed  Google Scholar 

  39. Boldt DH, Von Hoff DD, Kuhn JG, Hersh M . Effects on human peripheral lymphocytes of in vivo administration of 9-beta-D-arabinofuranosyl-2-fluoroadenine-5′-monophosphate (NSC 312887), a new purine antimetabolite. Cancer Res 1984; 44: 4661–4666.

    CAS  PubMed  Google Scholar 

  40. Keating MJ, O’Brien S, Lerner S, Koller C, Beran M, Robertson LE et al. Long-term follow-up of patients with chronic lymphocytic leukemia (CLL) receiving fludarabine regimens as initial therapy. Blood 1998; 92: 1165–1171.

    CAS  PubMed  Google Scholar 

  41. Larsen CR, Hansen PB, Clausen NT . Aggressive growth of epithelial carcinomas following treatment with nucleoside analogues. Am J Hematol 2002; 70: 48–50.

    Article  PubMed  Google Scholar 

  42. Davidovitz Y, Ballin A, Meytes D . Flare-up of squamous cell carcinoma of the skin following fludarabine therapy for chronic lymphocytic leukemia. Acta Haematol 1997; 98: 44–46.

    Article  CAS  PubMed  Google Scholar 

  43. Rashid K, Ng R, Mastan A, Sager D, Hirschman R . Accelerated growth of skin carcinoma following fludarabine therapy for chronic lymphocytic leukemia. Leuk Lymphoma 2005; 46: 1051–1055.

    Article  CAS  PubMed  Google Scholar 

  44. Gillison ML, Shah KV . Human papillomavirus-associated head and neck squamous cell carcinoma: mounting evidence for an etiologic role for human papillomavirus in a subset of head and neck cancers. Curr Opin Oncol 2001; 13: 183–188.

    Article  CAS  PubMed  Google Scholar 

  45. Scheffner M, Werness BA, Huibregtse JM, Levine AJ, Howley PM . The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 1990; 63: 1129–1136.

    Article  CAS  PubMed  Google Scholar 

  46. Kessis TD, Slebos RJ, Nelson WG, Kastan MB, Plunkett BS, Han SM et al. Human papillomavirus 16 E6 expression disrupts the p53-mediated cellular response to DNA damage. Proc Natl Acad Sci USA 1993; 90: 3988–3992.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Jones DL, Munger K . Analysis of the p53-mediated G1 growth arrest pathway in cells expressing the human papillomavirus type 16 E7 oncoprotein. J Virol 1997; 71: 2905–2912.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Kutler DI, Wreesmann VB, Goberdhan A, Ben-Porat L, Satagopan J, Ngai I et al. Human papillomavirus DNA and p53 polymorphisms in squamous cell carcinomas from Fanconi anemia patients. J Natl Cancer Inst 2003; 95: 1718–1721.

    Article  CAS  PubMed  Google Scholar 

  49. Ziegler A, Jonason AS, Leffell DJ, Simon JA, Sharma HW, Kimmelman J et al. Sunburn and p53 in the onset of skin cancer. Nature 1994; 372: 773–776.

    Article  CAS  PubMed  Google Scholar 

  50. Soehnge H, Ouhtit A, Ananthaswamy ON . Mechanisms of induction of skin cancer by UV radiation. Front Biosci 1997; 2: 538–551.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatric Hematology/Oncology, Indiana University School of Medicine, Indianapolis, IN, USA

    M Cavalier & R P Nelson Jr

  2. Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA

    J A Shmalo

  3. Department of Medicine, Division of Biostatistics, Indiana University School of Medicine and the IU Cancer Center, Indianapolis, IN, USA

    M Yu

  4. Departments of Pathology, Laboratory Medicine and Dermatology, Indiana University School of Medicine, Indianapolis, IN, USA

    S D Billings

  5. Division of Hematology/Oncology, Hematological Malignancy/Immunology and Stem Cell Transplant programs and the Indiana University Cancer Center, Indiana School of Medicine, Indianapolis, IN, USA

    R Abonour & R P Nelson Jr

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  1. M Cavalier
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Correspondence to R P Nelson Jr.

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Cavalier, M., Shmalo, J., Yu, M. et al. Skin cancer after nonmyeloablative hematopoietic cell transplantation. Bone Marrow Transplant 37, 1103–1108 (2006). https://doi.org/10.1038/sj.bmt.1705362

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  • DOI: https://doi.org/10.1038/sj.bmt.1705362

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