Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
5-Year IF – 2.0, IF – 1.9, JCI (2024) – 0.43
Scopus CiteScore – 4.3
Q1 in SJR 2024, SJR score – 0.598, H-index: 49 (SJR)
ICV – 161.00; MNiSW – 70 pts
Initial editorial assessment and first decision within 24 h

ISSN 1899–5276 (print), ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2020, vol. 29, nr 10, October, p. 1221–1230

doi: 10.17219/acem/126739

Publication type: review

Language: English

License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

Secondary skin neoplasms in patients after autologous and allogeneic hematopoietic stem cell transplantation procedures

Anastazja Szlauer-Stefańska1,A,B,C,D,E,F, Grażyna Kamińska-Winciorek1,A,B,D,E,F, Sebastian Giebel1,D,E,F, Maciej Bagłaj2,D,E,F

1 Department of Bone Marrow Transplantation and Oncohematology, Maria Sklodowska-Curie Institute – Oncology Center Gliwice Branch, Poland

2 Department of Pediatric Surgery and Urology, Wroclaw Medical University, Poland

Abstract

The increasing number of hematopoietic stem cell transplantation (HSCT) procedures and lower transplant-related mortality has led to a growing population of survivors facing long-term increased risk of secondary malignancy, including cutaneous neoplasms. In this review, we aim to discuss the incidence, risk factors and preventive strategies for secondary skin neoplasms after autologous and allogeneic HSCT. Cutaneous neoplasms, such as basal cell carcinoma, squamous cell carcinoma and melanoma, are among the most common solid cancers arising in patients after HSCT. Besides risk factors established in the general population, primary disease, chronic graft-versus-host disease (CGvHD), prolonged immunosuppression, especially with the use of cyclosporine and azathioprine, radiation exposure, light skin color, male sex, and young age at transplantation play a role in the development of cutaneous neoplasms in HSCT recipients. Skin cancer development after HSCT may be explained by cumulative effects of chemotherapy and radiotherapy-induced DNA damage, prolonged immunosuppressive conditions and chronic mucosal inflammation, particularly after allogeneic HSCT. Delayed immune recovery and persistent immunodeficiency in patients with graft-versus-host disease (GvHD) may also contribute to carcinogenesis. Regular dermatological surveillance and prompt recognition of precancerous and cancerous lesions is crucial for patient’s prognosis and management.

Key words

hematopoietic stem cell transplantation, skin neoplasms, graft-versus-host disease, basal cell carcinoma, squamous cell carcinoma

References (58)

  1. Gooley TA, Chien JW, Pergam SA, et al. Reduced mortality after allogeneic hematopoietic cell transplantation. N Engl J Med. 2010;363(22):2091–2101. doi:10.1056/NEJMoa1004383
  2. Mohty B, Mohty M. Long-term complications and side effects after allogeneic hematopoietic stem cell transplantation: An update. Blood Cancer J. 2011;1(4):e16–e25. doi:10.1038/bcj.2011.14
  3. Morton LM, Saber W, Baker KS, et al. National Institutes of Health Hematopoietic Cell Transplantation Late Effects Initiative: The Subsequent Neoplasms Working Group report. Biol Blood Marrow Transplant. 2017;23(3):367–378. doi:10.1016/j.bbmt.2016.09.005
  4. Baker KS, DeFor TE, Burns LJ, Ramsay NKC, Neglia JP, Robison LL. New malignancies after blood or marrow stem cell transplantation in children and adults: Incidence and risk factors. J Clin Oncol. 2003;21(7):1352–1358. doi:10.1200/JCO.2003.05.108
  5. Curtis RE, Rowlings PA, Deeg HJ, et al. Solid cancers after bone marrow transplantation. N Engl J Med. 1997;336(13):897–904. doi:10.1056/NEJM199703273361301
  6. Socié G, Baker KS, Bhatia S. Subsequent malignant neoplasms after hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2012;18(1 Suppl):S139–S150. doi:10.1016/j.bbmt.2011.10.005
  7. Bhatia S, Ramsay NK, Steinbuch M, et al. Malignant neoplasms following bone marrow transplantation. Blood. 1996;87(9):3633–3639. doi:10.1146/annurev.ecolsys.37.091305.110136
  8. Kolb HJ, Socié G, Duell T, et al. Malignant neoplasms in long-term survivors of bone marrow transplantation. Ann Intern Med. 1999;131(10):738–744. doi:10.7326/0003-4819-131-10-199911160-00004
  9. Kulkarni S, Powles R, Treleaven J, et al. Melphalan/TBI is not more carcinogenic than cyclophosphamide/TBI for transplant conditioning: Follow-up of 725 patients from a single centre over a period of 26 years. Bone Marrow Transplant. 2000;25(4):365–370. doi:10.1038/sj.bmt.1702148
  10. Bhatia S, Louie AD, Bhatia R, et al. Solid cancers after bone marrow transplantation. J Clin Oncol. 2001;19(2):464–471. doi:10.1200/JCO.2001.19.2.464
  11. Curtis RE, Metayer C, Rizzo JD, 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(10):3802–3811. doi:10.1182/blood-2004-09-3411
  12. Shimada K, Yokozawa T, Atsuta Y, et al. Solid tumors after hematopoietic stem cell transplantation in Japan: Incidence, risk factors and prognosis. Bone Marrow Transplant. 2005;36(2):115–121. doi:10.1038/sj.bmt.1705020
  13. 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(1):51–55. doi:10.1038/sj.bmt.1704706
  14. Brown JR, Yeckes H, Friedberg JW, et al. Increasing incidence of late second malignancies after conditioning with cyclophosphamide and total-body irradiation and autologous bone marrow transplantation for non-Hodgkin’s lymphoma. J Clin Oncol. 2005;23(10):2208–2214. doi:10.1200/JCO.2005.05.158
  15. Leisenring W, Friedman DL, Flowers MED, Schwartz JL, Deeg HJ. Nonmelanoma skin and mucosal cancers after hematopoietic cell transplantation. J Clin Oncol. 2006;24(7):1119–1126. doi:10.1200/JCO.2005.02.7052
  16. Cavalier M, Shmalo JA, Yu M, Billings SD, Abonour R, Nelson RP. Skin cancer after nonmyeloablative hematopoietic cell transplantation. Bone Marrow Transplant. 2006;37(12):1103–1108. doi:10.1038/sj.bmt.1705362
  17. Gallagher G, Forrest DL. Second solid cancers after allogeneic hematopoietic stem cell transplantation. Cancer. 2007;109(1):84–92. doi:10.1002/cncr.22375
  18. Schwartz JL, Kopecky KJ, Mathes RW, Leisenring WM, Friedman DL, Deeg HJ. Basal cell skin cancer after total-body irradiation and hematopoietic cell transplantation. Radiat Res. 2009;171(2):155–163. doi:10.1667/RR1469.1
  19. Rizzo JD, Curtis RE, Sobocinski KA, et al. Solid cancers after allogeneic hematopoietic cell transplantation. Blood. 2009;113(5):1175–1183. doi:10.1182/blood-2008-05-158782
  20. Abou-Mourad YR, Lau BC, Barnett MJ, et al. Long-term outcome after allo-SCT: Close follow-up on a large cohort treated with myeloablative regimens. Bone Marrow Transplant. 2010;45(2):295–302. doi:10.1038/bmt.2009.128
  21. Chen MH, Chang PM, Li WY, et al. High incidence of oral squamous cell carcinoma independent of HPV infection after allogeneic hematopoietic SCT in Taiwan. Bone Marrow Transplant. 2011;46(4):567–572. doi:10.1038/bmt.2010.163
  22. Majhail NS, Brazauskas R, Rizzo JD, et al. Secondary solid cancers after allogeneic hematopoietic cell transplantation using busulfan-cyclophosphamide conditioning. Blood. 2011;117(1):316–322. doi:10.1182/blood-2010-07-294629
  23. Yokota A, Ozawa S, Masanori T, et al; Kanto Study Group for Cell Therapy (KSGCT). Secondary solid tumors after allogeneic hematopoietic SCT in Japan. Bone Marrow Transplant. 2012;47(1):95–100. doi:10.1038/bmt.2011.23
  24. Shimoni A, Shem-Tov N, Chetrit A, et al. Secondary malignancies after allogeneic stem-cell transplantation in the era of reduced-intensity conditioning: The incidence is not reduced. Leukemia. 2013;27(4):829–835. doi:10.1038/leu.2012.299
  25. Krishnan AY, Mei M, Sun CL, et al. Second primary malignancies after autologous hematopoietic cell transplantation for multiple myeloma. Biol Blood Marrow Transplant. 2013;19(2):260–265. doi:10.1016/j.bbmt.2012.09.023
  26. Bilmon IA, Ashton LJ, Le Marsney RE, et al; CAST Study Group. Second cancer risk in adults receiving autologous haematopoietic SCT for cancer: A population-based cohort study. Bone Marrow Transplant. 2014;49(5):691–698. doi:10.1038/bmt.2014.13
  27. Atsuta Y, Suzuki R, Yamashita T, et al; Japan Society for Hematopoietic Cell Transplantation. Continuing increased risk of oral/esophageal cancer after allogeneic hematopoietic stem cell transplantation in adults in association with chronic graft-versus-host disease. Ann Oncol. 2014;25(2):435–441. doi:10.1093/annonc/mdt558
  28. Omland SH, Gniadecki R, Hædersdal M, Helweg-Larsen J, Omland LH. Skin cancer risk in hematopoietic stem cell transplant recipients compared with background population and renal transplant recipients. JAMA Dermatol. 2016;152(2):177–183. doi:10.1001/jamadermatol.2015.3902
  29. Michelis FV, Kotchetkov R, Grunwald RM, et al. Long-term incidence of secondary malignancies after allogeneic hematopoietic cell transplantation: A single-center experience. Biol Blood Marrow Transplant. 2017;23(6):945–951. doi:10.1016/j.bbmt.2017.02.015
  30. Song JS, London WB, Hawryluk EB, et al. Risk of melanocytic nevi and nonmelanoma skin cancer in children after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2017;52(7):989–997. doi:10.1038/bmt.2017.57
  31. Inamoto Y, Matsuda T, Tabuchi K, et al; Japan Society for ­Hematopoietic Cell Transplantation Late Effects and Quality of Life Working Group. Outcomes of patients who developed subsequent solid cancer after hematopoietic cell transplantation. Blood Adv. 2018;2(15):1901–1913. doi:10.1182/bloodadvances.2018020966
  32. DePry JL, Vyas R, Lazarus HM, Caimi PF, Gerstenblith MR, Bordeaux JS. Cutaneous malignant neoplasms in hematopoietic cell transplant recipients. JAMA Dermatol. 2015;151(7):775–782. doi:10.1001/jamadermatol.2015.121
  33. Majhail NS. Secondary cancers following allogeneic haematopoietic cell transplantation in adults. Br J Haematol. 2011;154(3):301–310. doi:10.1111/j.1365-2141.2011.08756.x
  34. Deeg HJ, Socié G, Schoch G, 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(1):386–392.
  35. Rangwala S, Tsai KY. Roles of the immune system in skin cancer. Br J Dermatol. 2011;165(5):953–965. doi:10.1111/j.1365-2133.2011.10507.x
  36. Sloand EM, Pfannes L, Ling C, et al. Graft-versus-host disease: Role of inflammation in the development of chromosomal abnormalities of keratinocytes. Biol Blood Marrow Transplant. 2010;16(12):1665–1673. doi:10.1016/j.bbmt.2010.07.014
  37. Vassallo C, Brazzelli V, Alessandrino PE, et al. Normal-looking skin in oncohaematological patients after allogenic bone marrow transplantation is not normal. Br J Dermatol. 2004;151(3):579–586. doi:10.1111/j.1365-2133.2004.06072.x
  38. Rambhia PH, Conic RZ, Atanaskova-Mesinkovska N, Piliang M, Bergfeld WF. Role of graft-versus-host disease in the development of secondary skin cancers in hematopoietic stem cell transplant recipients: A meta-analysis. J Am Acad Dermatol. 2018;79(2):378–380.e3. doi:10.1016/j.jaad.2018.01.012
  39. O’Donovan P. Azathioprine and UVA light generate mutagenic oxidative DNA damage. Science. 2005;309(5742):1871–1874. doi:10.1126/science.1114233
  40. Hojo M, Morimoto T, Maluccio M, et al. Cyclosporine induces cancer progression by a cell-autonomous mechanism. Nature. 1999;397(6719):530–534. doi:10.1038/17401
  41. Wojenski DJ, Bartoo GT, Merten JA, et al. Voriconazole exposure and the risk of cutaneous squamous cell carcinoma in allogeneic hematopoietic stem cell transplant patients. Transpl Infect Dis. 2015;17(2):250–258. doi:10.1111/tid.12367
  42. Epaulard O, Villier C, Ravaud P, et al. A multistep voriconazole-related phototoxic pathway may lead to skin carcinoma: Results from a French nationwide study. Clin Infect Dis. 2013;57(12):182–188. doi:10.1093/cid/cit600
  43. Meyer T, Arndt R, Nindl I, Ulrich C, Christophers E, Stockfleth E. Association of human papillomavirus infections with cutaneous tumors in immunosuppressed patients. Transpl Int. 2003;16(3):146–153. doi:10.1111/j.1432-2277.2003.tb00278.x
  44. Andreani V, Richard MA, Blaise D, Gouvernet J, Grob JJ. Naevi in allogeneic bone marrow transplantation recipients: The effect of graft-versus-host disease on naevi. Br J Dermatol. 2002;147(3):433–441. doi:10.1046/j.1365-2133.2002.04748.x
  45. Feily A, Namazi MR. Why is graft-versus-host disease sometimes associated with leukoderma and fewer melanocytic naevi? J Cosmet Dermatol. 2010;9(1):64–65. doi:10.1111/j.1473-2165.2010.00482.x
  46. Socié G, Henry-Amar M, Devergie A, et al. Poor clinical outcome of patients developing malignant solid tumors after bone marrow transplantation for severe aplastic anemia. Leuk Lymphoma. 1992;7(5–6):419–423. doi:10.3109/10428199209049797
  47. Brown SJ, Jackson GH, Reynolds NJ, Lawrence CM. Chronic cutaneous graft-versus-host disease associated with multiple cutaneous squamous cell carcinomas. Clin Exp Dermatol. 2006;31(3):472–473. doi:10.1111/j.1365-2230.2006.02109.x
  48. Altman JS, Adler SS. Development of multiple cutaneous squamous cell carcinomas during PUVA treatment for chronic graft-versus-host disease. J Am Acad Dermatol. 1994;31(3 Pt 1):505–507. doi:10.1016/S0190-9622(09)80014-5
  49. Perez HC, Benavides X, Perez JS, et al. Basic aspects of the pathogenesis and prevention of non-melanoma skin cancer in solid organ transplant recipients: A review. Int J Dermatol. 2017;56(4):370–378. doi:10.1111/ijd.13409
  50. Howard MD, Su JC, Chong AH. Skin cancer following solid organ transplantation: A review of risk factors and models of care. Am J Clin Dermatol. 2018;19(4):585–597. doi:10.1007/s40257-018-0355-8
  51. de Fijter JW. Cancer and mTOR Inhibitors in transplant recipients. Transplantation. 2018;101(1):45–55. doi:10.1097/TP.0000000000001447
  52. D’Souza A, Lee S, Zhu X, Pasquini M. Current use and trends in hematopoietic cell transplantation in the United States. Biol Blood Marrow Transplant. 2017;23(9):1417–1421. doi:10.1016/j.bbmt.2017.05.035
  53. Majhail NS, Rizzo JD, Lee SJ, et al. Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation. Bone Marrow Transplant. 2012;47(3):337–341. doi:10.1038/bmt.2012.5
  54. Inamoto Y, Shah NN, Savani BN, et al. Secondary solid cancer screening following hematopoietic cell transplantation. Bone Marrow Transplant. 2015;50(8):1013–1023. doi:10.1038/bmt.2015.63
  55. Marks C, Stadler M, Häusermann P, et al. German-Austrian-Swiss Consensus Conference on clinical practice in chronic graft-versus-host disease (GVHD): Guidance for supportive therapy of chronic cutaneous and musculoskeletal GVHD. Br J Dermatol. 2011;165(1):18–29. doi:10.1111/j.1365-2133.2011.10360.x
  56. Matin RN, Danby R, Gibbons E, et al. Developing a dedicated dermatology service for allogeneic bone marrow transplant recipients. Br J Dermatol. 2017;177(6):1758–1759. doi:10.1111/bjd.15343
  57. Savani BN, Griffith ML, Jagasia S, Lee SJ. How I treat late effects in adults after allogeneic stem cell transplantation. Blood. 2011;117(11):3002–3009. doi:10.1182/blood-2010-10-263095
  58. Bishop MM, Lee SJ, Beaumont JL, et al. The preventive health behaviors of long-term survivors of cancer and hematopoietic stem cell transplantation compared with matched controls. Biol Blood Marrow Transplant. 2010;16(2):207–214. doi:10.1016/j.bbmt.2009.09.015
© Wroclaw Medical University