Cutaneous T-Cell Lymphoma

  • Sasha Stephen
  • Ellen J. Kim
  • Camille E. Introcaso
  • Stephen K. Richardson
  • Alain H. Rook


Cutaneous T-cell lymphomas (CTCLs) are a group of extranodal non-Hodgkin’s lymphomas (NHLs) that present primarily in the skin. The most common type of CTCLs, mycosis fungoides (MF) and Sézary Syndrome (SS), were first described over two centuries ago, and since that time, the clinical characteristics, pathophysiology, and immunobiology have been characterized in detail. Derived from skin-homing, mature, effector T-cells that usually express CLA/CD4/CCR4/CCR10 and lack T-cell markers CD7 and/or CD26, the malignant MF/SS cells typically have a Th2 phenotype. With more advanced disease, Th2 cytokines predominate and result in decreased host cell-mediated immunity that likely contributes to increased susceptibility to infection and disease progression. Early aggressive systemic chemotherapy has not been shown to improve overall survival in MF/SS and over the past 40 years [1] the therapeutic approach has undergone a paradigm shift, such that skin-directed therapies (SDTs) and systemic immune-modifying biologics play a central role in initial MF/SS management. This chapter will review MF/SS clinical presentation, staging work-up, pathophysiology, immunobiology, and how these have shaped current treatment strategies. In particular, MF/SS chemokine biology, immune defects, and immune modifying therapies, including the new frontier of hematopoietic stem cell transplantation will be specifically highlighted.


Cutaneous T-Cell Lymphoma CTCL Non-Hodgkin’s lymphomas NHLs Mycosis fungoides MF Sézary Syndrome SS Dermatitis Psoriasis Parapsoriasis Skin condition Skin disease Tumor-node-metastasis-blood TNMB 


  1. 1.
    Kaye FJ, et al. A randomized trial comparing combination electron-beam radiation and chemotherapy with topical therapy in the initial treatment of mycosis fungoides. N Engl J Med. 1989;321(26):1784–90.PubMedCrossRefGoogle Scholar
  2. 2.
    Willemze R, et al. WHO-EORTC classification for cutaneous lymphomas. Blood. 2005;105(10):3768–85.PubMedCrossRefGoogle Scholar
  3. 3.
    Bradford PT, Devesa SS, Anderson WF, Toro JR. Cutaneous lymphoma incidence patterns in the United States: a population-based study of 3884 cases. Blood. 2009 May 21;113(21):5064–73. PubMed PMID: 19279331. Pubmed Central PMCID: 2686177. Epub 2009/03/13. eng.Google Scholar
  4. 4.
    Criscione VD, Weinstock MA. Incidence of cutaneous T-cell lymphoma in the United States, 1973–2002. Arch Dermatol. 2007 Jul;143(7):854–9. PubMed PMID: 17638728.Google Scholar
  5. 5.
    Girardi M, Heald PW, Wilson LD. The pathogenesis of mycosis fungoides. N Engl J Med. 2004;350(19):1978–88.PubMedCrossRefGoogle Scholar
  6. 6.
    Kim EJ, et al. Immunopathogenesis and therapy of cutaneous T cell lymphoma. J Clin Invest. 2005;115(4):798–812.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Kazakov DV, Burg G, Kempf W. Clinicopathological spectrum of mycosis fungoides. J Eur Acad Dermatol Venereol. 2004;18(4):397–415.PubMedCrossRefGoogle Scholar
  8. 8.
    Axelrod PI, Lorber B, Vonderheid EC. Infections complicating mycosis fungoides and Sezary syndrome. JAMA. 1992;267(10):1354–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Liu HL, et al. CD30+ cutaneous lymphoproliferative disorders: the Stanford experience in lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma. J Am Acad Dermatol. 2003;49(6):1049–58.PubMedCrossRefGoogle Scholar
  10. 10.
    Huang KP, et al. Second lymphomas and other malignant neoplasms in patients with mycosis fungoides and Sezary syndrome: evidence from population-based and clinical cohorts. Arch Dermatol. 2007;143(1):45–50.PubMedCrossRefGoogle Scholar
  11. 11.
    Ai WZ, Keegan TH, Press DJ, Yang J, Pincus LB, Kim YH, et al. Outcomes after diagnosis of mycosis fungoides and Sezary syndrome before 30 years of age: a population-based study. JAMA Dermatol. 2014 Jul;150(7):709–15. PubMed PMID: 24718769. Epub 2014/04/11. eng.Google Scholar
  12. 12.
    Wood GS, et al. Detection of clonal T-cell receptor gamma gene rearrangements in early mycosis fungoides/Sezary syndrome by polymerase chain reaction and denaturing gradient gel electrophoresis (PCR/DGGE). J Invest Dermatol. 1994;103(1):34–41.PubMedCrossRefGoogle Scholar
  13. 13.
    Pimpinelli N, et al. Defining early mycosis fungoides. J Am Acad Dermatol. 2005;53(6):1053–63.PubMedCrossRefGoogle Scholar
  14. 14.
    Ponti R, et al. T-cell receptor gamma gene rearrangement by multiplex polymerase chain reaction/heteroduplex analysis in patients with cutaneous T-cell lymphoma (mycosis fungoides/Sezary syndrome) and benign inflammatory disease: correlation with clinical, histological and immunophenotypical findings. Br J Dermatol. 2005;153(3):565–73.PubMedCrossRefGoogle Scholar
  15. 15.
    Alessi E, et al. The usefulness of clonality for the detection of cases clinically and/or histopathologically not recognized as cutaneous T-cell lymphoma. Br J Dermatol. 2005;153(2):368–71.PubMedCrossRefGoogle Scholar
  16. 16.
    Bernengo MG, et al. The relevance of the CD4+ CD26- subset in the identification of circulating Sezary cells. Br J Dermatol. 2001;144(1):125–35.PubMedCrossRefGoogle Scholar
  17. 17.
    Wysocka M, et al. CD164 and FCRL3 are highly expressed on CD4 + CD26- T cells in Sezary syndrome patients. J Invest Dermatol. 2014;134(1):229–36.PubMedCrossRefGoogle Scholar
  18. 18.
    Bagot M, et al. CD4(+) cutaneous T-cell lymphoma cells express the p140-killer cell immunoglobulin-like receptor. Blood. 2001;97(5):1388–91.PubMedCrossRefGoogle Scholar
  19. 19.
    Begue E, et al. Inducible expression and pathophysiologic functions of T-plastin in cutaneous T-cell lymphoma. Blood. 2012;120(1):143–54.PubMedCrossRefGoogle Scholar
  20. 20.
    van Doorn R, et al. Aberrant expression of the tyrosine kinase receptor EphA4 and the transcription factor twist in Sezary syndrome identified by gene expression analysis. Cancer Res. 2004;64(16):5578–86.PubMedCrossRefGoogle Scholar
  21. 21.
    Bensussan A, et al. Expression and function of the natural cytotoxicity receptor NKp46 on circulating malignant CD4+ T lymphocytes of Sezary syndrome patients. J Invest Dermatol. 2011;131(4):969–76.PubMedCrossRefGoogle Scholar
  22. 22.
    Michel L, et al. Use of PLS3, Twist, CD158k/KIR3DL2, and NKp46 gene expression combination for reliable Sezary syndrome diagnosis. Blood. 2013;121(8):1477–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Guitart J. Beyond clonal detection: defining the T-cell clone. Arch Dermatol. 2005;141(9):1159–60.PubMedCrossRefGoogle Scholar
  24. 24.
    Lamberg SI, Bunn Jr PA. Cutaneous T-cell lymphomas. Summary of the mycosis fungoides cooperative Group-National Cancer Institute Workshop. Arch Dermatol. 1979;115(9):1103–5.PubMedCrossRefGoogle Scholar
  25. 25.
    Vonderheid EC, Bernengo MG. The Sezary syndrome: hematologic criteria. Hematol Oncol Clin North Am. 2003;17(6):1367–89, viii.PubMedCrossRefGoogle Scholar
  26. 26.
    Vonderheid EC, Pena J, Nowell P. Sezary cell counts in erythrodermic cutaneous T-cell lymphoma: implications for prognosis and staging. Leuk Lymphoma. 2006;47(9):1841–56.PubMedCrossRefGoogle Scholar
  27. 27.
    Agar NS, et al. Survival outcomes and prognostic factors in mycosis fungoides/Sezary syndrome: validation of the revised International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer staging proposal. (1527–7755 (Electronic)).Google Scholar
  28. 28.
    Talpur R, Singh L, Daulat S, Liu P, Seyfer S, Trynosky T, et al. Long-term outcomes of 1,263 patients with mycosis fungoides and Sezary syndrome from 1982 to 2009. Clin Cancer Res. 2012 Sep 15;18(18):5051–60. PubMed PMID: 22850569. Pubmed Central PMCID: 3857608. Epub 2012/08/02. eng.Google Scholar
  29. 29.
    Kubica AW, Davis MD, Weaver AL, Killian JM, Pittelkow MR. Sezary syndrome: A study of 176 patients at Mayo Clinic. J Am Acad Dermatol. 2012 Dec;67(6):1189–99. PubMed PMID: 22640839. Epub 2012/05/30. eng.Google Scholar
  30. 30.
    National Comprehensive Cancer Network. Mycosis Fungoides/Sezary Syndrome Section in Non-Hodgkin’s Lymphoma (Version 3..2016). Accessed August 23, 2016.Google Scholar
  31. 31.
    Beylot-Barry M, et al. Is bone marrow biopsy necessary in patients with mycosis fungoides and Sezary syndrome? A histological and molecular study at diagnosis and during follow-up. Br J Dermatol. 2005;152(6):1378–9.PubMedCrossRefGoogle Scholar
  32. 32.
    Kim YH, et al. Long-term outcome of 525 patients with mycosis fungoides and Sezary syndrome: clinical prognostic factors and risk for disease progression. Arch Dermatol. 2003;139(7):857–66.PubMedCrossRefGoogle Scholar
  33. 33.
    Kim YH, et al. Clinical stage IA (limited patch and plaque) mycosis fungoides. A long-term outcome analysis. Arch Dermatol. 1996;132(11):1309–13.PubMedCrossRefGoogle Scholar
  34. 34.
    Kim YH, et al. Clinical characteristics and long-term outcome of patients with generalized patch and/or plaque (T2) mycosis fungoides. Arch Dermatol. 1999;135(1):26–32.PubMedCrossRefGoogle Scholar
  35. 35.
    Talpur R, Bassett R, Duvic M. Prevalence and treatment of Staphylococcus aureus colonization in patients with mycosis fungoides and Sezary syndrome. Br J Dermatol. 2008 Jul;159(1):105–12. PubMed PMID: 18489588.Google Scholar
  36. 36.
    Benner MF, Jansen PM, Vermeer MH, Willemze R. Prognostic factors in transformed mycosis fungoides: a retrospective analysis of 100 cases. Blood. 2012 Feb 16;119(7):1643–9. PubMed PMID: 22160616. Epub 2011/12/14. eng.Google Scholar
  37. 37.
    Benton EC, Crichton S, Talpur R, Agar NS, Fields PA, Wedgeworth E, et al. A cutaneous lymphoma international prognostic index (CLIPi) for mycosis fungoides and Sezary syndrome. Eur J Cancer. 2013 Sep;49(13):2859–68. PubMed PMID: 23735705. Epub 2013/06/06. eng.Google Scholar
  38. 38.
    Kari L, et al. Classification and prediction of survival in patients with the leukemic phase of cutaneous T cell lymphoma. J Exp Med. 2003;197(11):1477–88.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Nebozhyn M, Loboda A, Kari L, Rook AH, Vonderheid EC, Lessin S, et al. Quantitative PCR on 5 genes reliably identifies CTCL patients with 5% to 99% circulating tumor cells with 90% accuracy. Blood. 2006 Apr 15;107(8):3189–96. PubMed PMID: 16403914. Pubmed Central PMCID: 1464056. Epub 2006/01/13. eng.Google Scholar
  40. 40.
    Wong HK. Novel biomarkers, dysregulated epigenetics, and therapy in cutaneous T-cell lymphoma. Discovery medicine. 2013 Sep;16(87):71–8. PubMed PMID: 23998443.Google Scholar
  41. 41.
    Murdoch C, Finn A. Chemokine receptors and their role in inflammation and infectious diseases. Blood. 2000;95(10):3032–43.PubMedGoogle Scholar
  42. 42.
    Robert C, Kupper TS. Inflammatory skin diseases, T cells, and immune surveillance. N Engl J Med. 1999;341(24):1817–28.PubMedCrossRefGoogle Scholar
  43. 43.
    Ferenczi K, et al. Increased CCR4 expression in cutaneous T cell lymphoma. J Invest Dermatol. 2002;119(6):1405–10.PubMedCrossRefGoogle Scholar
  44. 44.
    Poznansky MC, et al. Active movement of T cells away from a chemokine. Nat Med. 2000;6(5):543–8.PubMedCrossRefGoogle Scholar
  45. 45.
    Kallinich T, et al. Chemokine receptor expression on neoplastic and reactive T cells in the skin at different stages of mycosis fungoides. J Invest Dermatol. 2003;121(5):1045–52.PubMedCrossRefGoogle Scholar
  46. 46.
    Morales J, et al. CTACK, a skin-associated chemokine that preferentially attracts skin-homing memory T cells. Proc Natl Acad Sci U S A. 1999;96(25):14470–5.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Sokolowska-Wojdylo M, et al. Circulating clonal CLA(+) and CD4(+) T cells in Sezary syndrome express the skin-homing chemokine receptors CCR4 and CCR10 as well as the lymph node-homing chemokine receptor CCR7. Br J Dermatol. 2005;152(2):258–64.PubMedCrossRefGoogle Scholar
  48. 48.
    Duvic M, Tetzlaff MT, Gangar P, Clos AL, Sui D, Talpur R. Results of a Phase II Trial of Brentuximab Vedotin for CD30+ Cutaneous T-Cell Lymphoma and Lymphomatoid Papulosis. J Clin Oncol. 2015 Nov 10;33(32):3759–65. PubMed PMID: 26261247. Pubmed Central PMCID: 4737859.Google Scholar
  49. 49.
    Richardson SK, Newton SB, Bach TL, Budgin JB, Benoit BM, Lin JH, et al. Bexarotene blunts malignant T-cell chemotaxis in Sezary syndrome: reduction of chemokine receptor 4-positive lymphocytes and decreased chemotaxis to thymus and activation-regulated chemokine. Am J Hematol. 2007 Sep;82(9):792–7. PubMed PMID: 17546636. Epub 2007/06/05. eng.Google Scholar
  50. 50.
    Campbell JJ, Clark RA, Watanabe R, Kupper TS. Sezary syndrome and mycosis fungoides arise from distinct T-cell subsets: a biologic rationale for their distinct clinical behaviors. Blood. 2010 Aug 5;116(5):767–71. PubMed PMID: 20484084. Pubmed Central PMCID: 2918332. Epub 2010/05/21. eng.Google Scholar
  51. 51.
    van Doorn R, van Kester MS, Dijkman R, Vermeer MH, Mulder AA, Szuhai K, et al. Oncogenomic analysis of mycosis fungoides reveals major differences with Sezary syndrome. Blood. 2009 Jan 1;113(1):127–36. PubMed PMID: 18832135.Google Scholar
  52. 52.
    Vermeer MH, van Doorn R, Dijkman R, Mao X, Whittaker S, van Voorst Vader PC, et al. Novel and highly recurrent chromosomal alterations in Sezary syndrome. Cancer Res. 2008 Apr 15;68(8):2689–98. PubMed PMID: 18413736. Epub 2008/04/17. eng.Google Scholar
  53. 53.
    Introcaso CE, et al. Association of change in clinical status and change in the percentage of the CD4 + CD26- lymphocyte population in patients with Sezary syndrome. J Am Acad Dermatol. 2005;53(3):428–34.PubMedCrossRefGoogle Scholar
  54. 54.
    Kagami S, Sugaya M, Minatani Y, Ohmatsu H, Kakinuma T, Fujita H, et al. Elevated serum CTACK/CCL27 levels in CTCL. J Invest Dermatol. 2006 May;126(5):1189–91. PubMed PMID: 16528355.Google Scholar
  55. 55.
    Homey B, et al. CCL27-CCR10 interactions regulate T cell-mediated skin inflammation. Nat Med. 2002;8(2):157–65.PubMedCrossRefGoogle Scholar
  56. 56.
    Notohamiprodjo M, et al. CCR10 is expressed in cutaneous T-cell lymphoma. Int J Cancer. 2005;115(4):641–7.PubMedCrossRefGoogle Scholar
  57. 57.
    Kakinuma T, et al. Thymus and activation-regulated chemokine (TARC/CCL17) in mycosis fungoides: serum TARC levels reflect the disease activity of mycosis fungoides. J Am Acad Dermatol. 2003;48(1):23–30.PubMedCrossRefGoogle Scholar
  58. 58.
    Tensen CP, et al. Epidermal interferon-gamma inducible protein-10 (IP-10) and monokine induced by gamma-interferon (Mig) but not IL-8 mRNA expression is associated with epidermotropism in cutaneous T cell lymphomas. J Invest Dermatol. 1998;111(2):222–6.PubMedCrossRefGoogle Scholar
  59. 59.
    Yamanaka K, et al. Skin-derived interleukin-7 contributes to the proliferation of lymphocytes in cutaneous T-cell lymphoma. Blood. 2006;107(6):2440–5.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Smoller BR, et al. Histopathology and genetics of cutaneous T-cell lymphoma. Hematol Oncol Clin North Am. 2003;17(6):1277–311.PubMedCrossRefGoogle Scholar
  61. 61.
    Sommer VH, et al. In vivo activation of STAT3 in cutaneous T-cell lymphoma. Evidence for an antiapoptotic function of STAT3. Leukemia. 2004;18(7):1288–95.PubMedCrossRefGoogle Scholar
  62. 62.
    Dereure O, et al. Infrequent Fas mutations but no Bax or p53 mutations in early mycosis fungoides: a possible mechanism for the accumulation of malignant T lymphocytes in the skin. J Invest Dermatol. 2002;118(6):949–56.PubMedCrossRefGoogle Scholar
  63. 63.
    Ni X, et al. Resistance to activation-induced cell death and bystander cytotoxicity via the Fas/Fas ligand pathway are implicated in the pathogenesis of cutaneous T cell lymphomas. J Invest Dermatol. 2005;124(4):741–50.PubMedCrossRefGoogle Scholar
  64. 64.
    van Doorn R, et al. Epigenetic profiling of cutaneous T-cell lymphoma: promoter hypermethylation of multiple tumor suppressor genes including BCL7a, PTPRG, and p73. J Clin Oncol. 2005;23(17):3886–96.PubMedCrossRefGoogle Scholar
  65. 65.
    Nagasawa T, et al. Multi-gene epigenetic silencing of tumor suppressor genes in T-cell lymphoma cells; delayed expression of the p16 protein upon reversal of the silencing. Leuk Res. 2006;30(3):303–12.PubMedCrossRefGoogle Scholar
  66. 66.
    Sors A, et al. Down-regulating constitutive activation of the NF-kappaB canonical pathway overcomes the resistance of cutaneous T-cell lymphoma to apoptosis. Blood. 2006;107(6):2354–63.PubMedCrossRefGoogle Scholar
  67. 67.
    Rosato RR, Grant S. Histone deacetylase inhibitors: insights into mechanisms of lethality. Expert Opin Ther Targets. 2005;9(4):809–24.PubMedCrossRefGoogle Scholar
  68. 68.
    Talpur R, et al. CD25 expression is correlated with histological grade and response to denileukin diftitox in cutaneous T-cell lymphoma. J Invest Dermatol. 2006;126(3):575–83.PubMedCrossRefGoogle Scholar
  69. 69.
    Wasik MA, et al. Increased serum concentration of the soluble interleukin-2 receptor in cutaneous T-cell lymphoma. Clinical and prognostic implications. Arch Dermatol. 1996;132(1):42–7.PubMedCrossRefGoogle Scholar
  70. 70.
    Vowels BR, et al. Aberrant cytokine production by Sezary syndrome patients: cytokine secretion pattern resembles murine Th2 cells. J Invest Dermatol. 1992;99(1):90–4.PubMedCrossRefGoogle Scholar
  71. 71.
    Vowels BR, et al. Th2 cytokine mRNA expression in skin in cutaneous T-cell lymphoma. J Invest Dermatol. 1994;103(5):669–73.PubMedCrossRefGoogle Scholar
  72. 72.
    Asadullah K, et al. Progression of mycosis fungoides is associated with increasing cutaneous expression of interleukin-10 mRNA. J Invest Dermatol. 1996;107(6):833–7.PubMedCrossRefGoogle Scholar
  73. 73.
    Hoppe RT, et al. CD8-positive tumor-infiltrating lymphocytes influence the long-term survival of patients with mycosis fungoides. J Am Acad Dermatol. 1995;32(3):448–53.PubMedCrossRefGoogle Scholar
  74. 74.
    Zackheim HS, et al. Psoriasiform mycosis fungoides with fatal outcome after treatment with cyclosporine. J Am Acad Dermatol. 2002;47(1):155–7.PubMedCrossRefGoogle Scholar
  75. 75.
    Wysocka M, et al. Sezary syndrome patients demonstrate a defect in dendritic cell populations: effects of CD40 ligand and treatment with GM-CSF on dendritic cell numbers and the production of cytokines. Blood. 2002;100(9):3287–94.PubMedCrossRefGoogle Scholar
  76. 76.
    Yamanaka K, et al. Expression of interleukin-18 and caspase-1 in cutaneous T-cell lymphoma. Clin Cancer Res. 2006;12(2):376–82.PubMedCrossRefGoogle Scholar
  77. 77.
    Berger CL, Tigelaar R, Cohen J, Mariwalla K, Trinh J, Wang N, et al. Cutaneous T-cell lymphoma: malignant proliferation of T-regulatory cells. Blood. 2005 Feb 15;105(4):1640–7. PubMed PMID: 15514008.Google Scholar
  78. 78.
    Walsh PT, et al. A role for regulatory T cells in cutaneous T-Cell lymphoma; induction of a CD4 + CD25 + Foxp3+ T-cell phenotype associated with HTLV-1 infection. J Invest Dermatol. 2006;126(3):690–2.PubMedCrossRefGoogle Scholar
  79. 79.
    Wong HK, et al. Increased expression of CTLA-4 in malignant T-cells from patients with mycosis fungoides – cutaneous T cell lymphoma. J Invest Dermatol. 2006;126(1):212–9.PubMedCrossRefGoogle Scholar
  80. 80.
    Tiemessen MM, et al. Lack of suppressive CD4 + CD25 + FOXP3+ T cells in advanced stages of primary cutaneous T-cell lymphoma. J Invest Dermatol. 2006;126(10):2217–23.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Yamano Y, et al. Virus-induced dysfunction of CD4 + CD25+ T cells in patients with HTLV-I-associated neuroimmunological disease. J Clin Invest. 2005;115(5):1361–8.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    French LE, et al. Impaired CD40L signaling is a cause of defective IL-12 and TNF-{alpha} production in Sezary syndrome: circumvention by hexameric soluble CD40L. Blood. 2005;105(1):219–25.PubMedCrossRefGoogle Scholar
  83. 83.
    Yawalkar N, et al. Profound loss of T-cell receptor repertoire complexity in cutaneous T-cell lymphoma. Blood. 2003;102(12):4059–66.PubMedCrossRefGoogle Scholar
  84. 84.
    Yamanaka K, et al. Decreased T-cell receptor excision circles in cutaneous T-cell lymphoma. Clin Cancer Res. 2005;11(16):5748–55.PubMedCrossRefGoogle Scholar
  85. 85.
    Yoo EK, et al. Complete molecular remission during biologic response modifier therapy for Sezary syndrome is associated with enhanced helper T type 1 cytokine production and natural killer cell activity. J Am Acad Dermatol. 2001;45(2):208–16.PubMedCrossRefGoogle Scholar
  86. 86.
    Wysocka M, et al. Enhancement of the host immune responses in cutaneous T-cell lymphoma by CpG oligodeoxynucleotides and IL-15. Blood. 2004;104(13):4142–9.PubMedCrossRefGoogle Scholar
  87. 87.
    Goldgeier MH, et al. An unusual and fatal case of disseminated cutaneous herpes simplex. Infection in a patient with cutaneous T cell lymphoma (mycosis fungoides). J Am Acad Dermatol. 1981;4(2):176–80.PubMedCrossRefGoogle Scholar
  88. 88.
    Lee J, et al. Progressive multifocal leukoencephalopathy (JC virus) in a patient with advanced mycosis fungoides. J Am Acad Dermatol (submitted). 2007.Google Scholar
  89. 89.
    Evans AV, et al. Cutaneous malignant melanoma in association with mycosis fungoides. J Am Acad Dermatol. 2004;50(5):701–5.PubMedCrossRefGoogle Scholar
  90. 90.
    Pielop JA, Brownell I, Duvic M. Mycosis fungoides associated with malignant melanoma and dysplastic nevus syndrome. Int J Dermatol. 2003;42(2):116–22.PubMedCrossRefGoogle Scholar
  91. 91.
    Molin L, Thomsen K, Volden G. Serum IgE in mycosis fungoides. Br Med J. 1978;1(6117):920–1.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Tancrede-Bohin E, et al. Prognostic value of blood eosinophilia in primary cutaneous T-cell lymphomas. Arch Dermatol. 2004;140(9):1057–61.PubMedCrossRefGoogle Scholar
  93. 93.
    Suchin KR, et al. Increased interleukin 5 production in eosinophilic Sezary syndrome: regulation by interferon alfa and interleukin 12. J Am Acad Dermatol. 2001;44(1):28–32.PubMedCrossRefGoogle Scholar
  94. 94.
    Kim YH, et al. Topical nitrogen mustard in the management of mycosis fungoides: update of the Stanford experience. Arch Dermatol. 2003;139(2):165–73.PubMedGoogle Scholar
  95. 95.
    Zackheim HS. Topical carmustine (BCNU) for patch/plaque mycosis fungoides. Semin Dermatol. 1994;13(3):202–6.PubMedGoogle Scholar
  96. 96.
    Zhang C, Duvic M. Retinoids: therapeutic applications and mechanisms of action in cutaneous T-cell lymphoma. Dermatol Ther. 2003;16(4):322–30.PubMedCrossRefGoogle Scholar
  97. 97.
    Herrmann JJ, et al. Treatment of mycosis fungoides with photochemotherapy (PUVA): long-term follow-up. J Am Acad Dermatol. 1995;33(2 Pt 1):234–42.PubMedCrossRefGoogle Scholar
  98. 98.
    Querfeld C, et al. Long-term follow-up of patients with early-stage cutaneous T-cell lymphoma who achieved complete remission with psoralen plus UV-A monotherapy. Arch Dermatol. 2005;141(3):305–11.PubMedCrossRefGoogle Scholar
  99. 99.
    Jones G, Wilson LD, Fox-Goguen L. Total skin electron beam radiotherapy for patients who have mycosis fungoides. Hematol Oncol Clin North Am. 2003;17(6):1421–34.PubMedCrossRefGoogle Scholar
  100. 100.
    McGinnis KS, et al. Psoralen plus long-wave UV-A (PUVA) and bexarotene therapy: an effective and synergistic combined adjunct to therapy for patients with advanced cutaneous T-cell lymphoma. Arch Dermatol. 2003;139(6):771–5.PubMedCrossRefGoogle Scholar
  101. 101.
    McGinnis KS, et al. Low-dose oral bexarotene in combination with low-dose interferon alfa in the treatment of cutaneous T-cell lymphoma: clinical synergism and possible immunologic mechanisms. J Am Acad Dermatol. 2004;50(3):375–9.PubMedCrossRefGoogle Scholar
  102. 102.
    Singh F, Lebwohl MG. Cutaneous T-cell lymphoma treatment using bexarotene and PUVA: a case series. J Am Acad Dermatol. 2004;51(4):570–3.PubMedCrossRefGoogle Scholar
  103. 103.
    Rupoli S, et al. Long-term experience with low-dose interferon-alpha and PUVA in the management of early mycosis fungoides. Eur J Haematol. 2005;75(2):136–45.PubMedCrossRefGoogle Scholar
  104. 104.
    Rook AH, Kuzel TM, Olsen EA. Cytokine therapy of cutaneous T-cell lymphoma: interferons, interleukin-12, and interleukin-2. Hematol Oncol Clin North Am. 2003;17(6):1435–48, ix.PubMedCrossRefGoogle Scholar
  105. 105.
    Kuzel TM, et al. Effectiveness of interferon alfa-2a combined with phototherapy for mycosis fungoides and the Sezary syndrome. J Clin Oncol. 1995;13(1):257–63.PubMedCrossRefGoogle Scholar
  106. 106.
    Chiarion-Sileni V, et al. Phase II trial of interferon-alpha-2a plus psolaren with ultraviolet light A in patients with cutaneous T-cell lymphoma. Cancer. 2002;95(3):569–75.PubMedCrossRefGoogle Scholar
  107. 107.
    Knobler RM, et al. Treatment of cutaneous T cell lymphoma with a combination of low-dose interferon alfa-2b and retinoids. J Am Acad Dermatol. 1991;24(2 Pt 1):247–52.PubMedCrossRefGoogle Scholar
  108. 108.
    Wu J, Wood GS. Reduction of Fas/CD95 promoter methylation, upregulation of Fas protein, and enhancement of sensitivity to apoptosis in cutaneous T-cell lymphoma. Arch Dermatol. 2011 Apr;147(4):443–9. PubMed PMID: 21173302. Epub 2010/12/22. eng.Google Scholar
  109. 109.
    Aviles A, Nambo MJ, Neri N, Castaneda C, Cleto S, Gonzalez M, et al. Interferon and low dose methotrexate improve outcome in refractory mycosis fungoides/Sezary syndrome. Cancer Biother Radiopharm. 2007 Dec;22(6):836–40. PubMed PMID: 18158775. Epub 2007/12/27. eng.Google Scholar
  110. 110.
    Zhang C, et al. Induction of apoptosis by bexarotene in cutaneous T-cell lymphoma cells: relevance to mechanism of therapeutic action. Clin Cancer Res. 2002;8(5):1234–40.PubMedGoogle Scholar
  111. 111.
    Budgin JB, et al. Biological effects of bexarotene in cutaneous T-cell lymphoma. Arch Dermatol. 2005;141(3):315–21.PubMedCrossRefGoogle Scholar
  112. 112.
    Duvic M, et al. Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: multinational phase II-III trial results. J Clin Oncol. 2001;19(9):2456–71.PubMedCrossRefGoogle Scholar
  113. 113.
    Lin JH, Kim EJ, Bansal A, Seykora J, Richardson SK, Cha XY, et al. Clinical and in vitro resistance to bexarotene in adult T-cell leukemia: loss of RXR-alpha receptor. Blood. 2008 Sep 15;112(6):2484–8. PubMed PMID: 18559673. Pubmed Central PMCID: 2532815. Epub 2008/06/19. eng.Google Scholar
  114. 114.
    Fox FE, et al. Retinoids synergize with interleukin-2 to augment IFN-gamma and interleukin-12 production by human peripheral blood mononuclear cells. J Interferon Cytokine Res. 1999;19(4):407–15.PubMedCrossRefGoogle Scholar
  115. 115.
    Krieg AM. Development of TLR9 agonists for cancer therapy. J Clin Invest. 2007;117(5):1184–94.PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Wysocka M, et al. Synthetic imidazoquinolines enhance the cell-mediated immune responses of cutaneous T-cell lymphoma patients via Toll-like receptors: synergy with IFN-gamma enhances production of IL-12. J Invest Dermatol (submitted). 2007.Google Scholar
  117. 117.
    Suchin KR, Junkins-Hopkins JM, Rook AH. Treatment of stage IA cutaneous T-Cell lymphoma with topical application of the immune response modifier imiquimod. Arch Dermatol. 2002;138(9):1137–9.PubMedCrossRefGoogle Scholar
  118. 118.
    Dummer R, et al. Imiquimod induces complete clearance of a PUVA-resistant plaque in mycosis fungoides. Dermatology. 2003;207(1):116–8.PubMedCrossRefGoogle Scholar
  119. 119.
    Hurwitz DJ, Pincus L, Kupper TS. Imiquimod: a topically applied link between innate and acquired immunity. Arch Dermatol. 2003;139(10):1347–50.PubMedCrossRefGoogle Scholar
  120. 120.
    Kawai T, et al. Interferon-alpha induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6. Nat Immunol. 2004;5(10):1061–8.PubMedCrossRefGoogle Scholar
  121. 121.
    Schon MP, Schon M. Immune modulation and apoptosis induction: two sides of the antitumoral activity of imiquimod. Apoptosis. 2004;9(3):291–8.PubMedCrossRefGoogle Scholar
  122. 122.
    Rook AH. The beauty of TLR agonists for CTCL. Blood. 2012;119(2):321–2.PubMedCrossRefGoogle Scholar
  123. 123.
    Richardson SK, et al. High clinical response rate with multimodality immunomodulatory therapy for Sezary syndrome. Clin Lymphoma Myeloma. 2006;7(3):226–32.PubMedCrossRefGoogle Scholar
  124. 124.
    Suchin KR, et al. Treatment of cutaneous T-cell lymphoma with combined immunomodulatory therapy: a 14-year experience at a single institution. Arch Dermatol. 2002;138(8):1054–60.PubMedCrossRefGoogle Scholar
  125. 125.
    Yoo EK, et al. Apoptosis induction of ultraviolet light A and photochemotherapy in cutaneous T-cell lymphoma: relevance to mechanism of therapeutic action. J Invest Dermatol. 1996;107(2):235–42.PubMedCrossRefGoogle Scholar
  126. 126.
    Heald PW, Edelson RL. Photopheresis for T cell mediated diseases. Adv Dermatol. 1988;3:25–40.PubMedGoogle Scholar
  127. 127.
    Girardi M, et al. Transimmunization for cutaneous T cell lymphoma: a Phase I study. Leuk Lymphoma. 2006;47(8):1495–503.PubMedCrossRefGoogle Scholar
  128. 128.
    Kim S, Elkon KB, Ma X. Transcriptional suppression of interleukin-12 gene expression following phagocytosis of apoptotic cells. Immunity. 2004;21(5):643–53.PubMedCrossRefGoogle Scholar
  129. 129.
    Raphael BA, Shin DB, Suchin KR, Morrissey KA, Vittorio CC, Kim EJ, et al. High clinical response rate of Sezary syndrome to immunomodulatory therapies: prognostic markers of response. Arch Dermatol. 2011 Dec;147(12):1410–5. PubMed PMID: 21844430. Epub 2011/08/17. eng.Google Scholar
  130. 130.
    Kaplan EH, et al. Phase II study of recombinant human interferon gamma for treatment of cutaneous T-cell lymphoma. J Natl Cancer Inst. 1990;82(3):208–12.PubMedCrossRefGoogle Scholar
  131. 131.
    McGinnis KS, et al. The addition of interferon gamma to oral bexarotene therapy with photopheresis for Sezary syndrome. Arch Dermatol. 2005;141(9):1176–8.PubMedCrossRefGoogle Scholar
  132. 132.
    Shapiro M, et al. Novel multimodality biologic response modifier therapy, including bexarotene and long-wave ultraviolet A for a patient with refractory stage IVa cutaneous T-cell lymphoma. J Am Acad Dermatol. 2002;47(6):956–61.PubMedCrossRefGoogle Scholar
  133. 133.
    Wysocka M, et al. Synergistic enhancement of cellular immune responses by the novel Toll receptor 7/8 agonist 3 M-007 and interferon-gamma: implications for therapy of cutaneous T-cell lymphoma. Leuk Lymphoma. 2011;52(10):1970–9.PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.
    Dummer R, et al. Adenovirus-mediated intralesional interferon-gamma gene transfer induces tumor regressions in cutaneous lymphomas. Blood. 2004;104(6):1631–8.PubMedCrossRefGoogle Scholar
  135. 135.
    vanderSpek JC, et al. Structure/function analysis of the transmembrane domain of DAB389-interleukin-2, an interleukin-2 receptor-targeted fusion toxin. The amphipathic helical region of the transmembrane domain is essential for the efficient delivery of the catalytic domain to the cytosol of target cells. J Biol Chem. 1993;268(16):12077–82.Google Scholar
  136. 136.
    Olsen E, et al. Pivotal phase III trial of two dose levels of denileukin diftitox for the treatment of cutaneous T-cell lymphoma. J Clin Oncol. 2001;19(2):376–88.PubMedCrossRefGoogle Scholar
  137. 137.
    Dannull J, et al. Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells. J Clin Invest. 2005;115(12):3623–33.PubMedPubMedCentralCrossRefGoogle Scholar
  138. 138.
    Camacho LH, Ribas A, Glaspy JA, Lopez-Berestein G, Reuben JM, Parker C, Seja E, Comin-Anduix B, Bulanhagui C, Gomez-Navarro J. Phase 1 clinical trial of anti-CTLA4 human monoclonal antibody CP-675,206 in patients with advanced solid malignancies. J Clin Oncol. 2004;22(14S):2505.Google Scholar
  139. 139.
    Phan GQ, et al. Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc Natl Acad Sci U S A. 2003;100(14):8372–7.PubMedPubMedCentralCrossRefGoogle Scholar
  140. 140.
    Querfeld C, Mehta N, Rosen ST, Guitart J, Rademaker A, Gerami P, et al. Alemtuzumab for relapsed and refractory erythrodermic cutaneous T-cell lymphoma: a single institution experience from the Robert H. Lurie Comprehensive Cancer Center. Leuk Lymphoma. 2009 Dec;50(12):1969–76. PubMed PMID: 19860617. Epub 2009/10/29. eng.Google Scholar
  141. 141.
    Clark RA, Watanabe R, Teague JE, Schlapbach C, Tawa MC, Adams N, et al. Skin effector memory T cells do not recirculate and provide immune protection in alemtuzumab-treated CTCL patients. Sci Transl Med. 2012 Jan 18;4(117):117ra7. PubMed PMID: 22261031. Pubmed Central PMCID: 3373186. Epub 2012/01/21. eng.Google Scholar
  142. 142.
    de Masson A, Guitera P, Brice P, Moulonguet I, Mouly F, Bouaziz JD, et al. Long-term efficacy and safety of alemtuzumab in advanced primary cutaneous T-cell lymphomas. Br J Dermatol. 2014 Mar;170(3):720–4. PubMed PMID: 24438061.Google Scholar
  143. 143.
    Faguer S, Launay F, Ysebaert L, Mailhol C, Estines-Chartier O, Lamant L, et al. Acute cutaneous T-cell lymphoma transformation during treatment with alemtuzumab. Br J Dermatol. 2007 Oct;157(4):841–2. PubMed PMID: 17714563.Google Scholar
  144. 144.
    Fernandes IC, Goncalves M, dos Anjos Teixeira M, Goncalves C, Coutinho J, Selores M, et al. Can the level of CD52 expression on Sezary cells be used to predict the response of Sezary syndrome to alemtuzumab? J Am Acad Dermatol. 2012 Nov;67(5):1083–5. PubMed PMID: 23062898. Epub 2012/10/16. eng.Google Scholar
  145. 145.
    Clodi K, Younes A. Reed-Sternberg cells and the TNF family of receptors/ligands. Leuk Lymphoma. 1997 Oct;27(3–4):195–205. PubMed PMID: 9402319.Google Scholar
  146. 146.
    Duvic M, Tavallaee M, Gangar P, Clos A, Talpur R. Phase II trial of Brentuximab vedotin (SGN-35) for CD30+ cutaneous T-cell lymphomas and lymphoproliferative disorders. J Invest Dermatol. 2013;133(S180).Google Scholar
  147. 147.
    von Geldern G, Pardo CA, Calabresi PA, Newsome SD. PML-IRIS in a patient treated with brentuximab. Neurology. 2012 Nov 13;79(20):2075–7. PubMed PMID: 23115213. Pubmed Central PMCID: 3511922.Google Scholar
  148. 148.
    Carson KR, Newsome SD, Kim EJ, Wagner-Johnston ND, von Geldern G, Moskowitz CH, et al. Progressive multifocal leukoencephalopathy associated with brentuximab vedotin therapy: a report of 5 cases from the Southern Network on Adverse Reactions (SONAR) project. Cancer. 2014 Aug 15;120(16):2464–71. PubMed PMID: 24771533. Pubmed Central PMCID: 4460831.Google Scholar
  149. 149.
    Xu WS, Parmigiani RB, Marks PA. Histone deacetylase inhibitors: molecular mechanisms of action. Oncogene. 2007 Aug 13;26(37):5541–52. PubMed PMID: 17694093.Google Scholar
  150. 150.
    Olsen EA, Kim YH, Kuzel TM, Pacheco TR, Foss FM, Parker S, et al. Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma. J Clin Oncol. 2007 Jul 20;25(21):3109–15. PubMed PMID: 17577020. Epub 2007/06/20. eng.Google Scholar
  151. 151.
    Glauben R, Batra A, Fedke I, Zeitz M, Lehr HA, Leoni F, et al. Histone hyperacetylation is associated with amelioration of experimental colitis in mice. Journal of immunology. 2006 Apr 15;176(8):5015–22. PubMed PMID: 16585598.Google Scholar
  152. 152.
    Reddy P, Maeda Y, Hotary K, Liu C, Reznikov LL, Dinarello CA, et al. Histone deacetylase inhibitor suberoylanilide hydroxamic acid reduces acute graft-versus-host disease and preserves graft-versus-leukemia effect. Proc Natl Acad Sci U S A. 2004 Mar 16;101(11):3921–6. PubMed PMID: 15001702. Pubmed Central PMCID: 374345.Google Scholar
  153. 153.
    Mishra N, Reilly CM, Brown DR, Ruiz P, Gilkeson GS. Histone deacetylase inhibitors modulate renal disease in the MRL-lpr/lpr mouse. J Clin Invest. 2003 Feb;111(4):539–52. PubMed PMID: 12588892. Pubmed Central PMCID: 151922.Google Scholar
  154. 154.
    Tao R, de Zoeten EF, Ozkaynak E, Chen C, Wang L, Porrett PM, et al. Deacetylase inhibition promotes the generation and function of regulatory T cells. Nature medicine. 2007 Nov;13(11):1299–307. PubMed PMID: 17922010.Google Scholar
  155. 155.
    Gardner JM, Evans KG, Goldstein S, Kim EJ, Vittorio CC, Rook AH. Vorinostat for the treatment of bullous pemphigoid in the setting of advanced, refractory cutaneous T-cell lymphoma. Arch Dermatol. 2009 Sep;145(9):985–8. PubMed PMID: 19770436. Epub 2009/09/23. eng.Google Scholar
  156. 156.
    Leoni F, Fossati G, Lewis EC, Lee JK, Porro G, Pagani P, et al. The histone deacetylase inhibitor ITF2357 reduces production of pro-inflammatory cytokines in vitro and systemic inflammation in vivo. Molecular medicine. 2005 Jan-Dec;11(1–12):1–15. PubMed PMID: 16557334. Pubmed Central PMCID: 1449516.Google Scholar
  157. 157.
    Stephen S, et al. Inhibition of cell-mediated immunity by the histone deacetylase inhibitor vorinostat: implications for therapy of cutaneous T-cell lymphoma. Am J Hematol. 2012;87(2):226–8.PubMedCrossRefGoogle Scholar
  158. 158.
    Kelly-Sell MJ, et al. The histone deacetylase inhibitor, romidepsin, suppresses cellular immune functions of cutaneous T-cell lymphoma patients. Am J Hematol. 2012;87(4):354–60.PubMedPubMedCentralCrossRefGoogle Scholar
  159. 159.
    Ritchie D, Piekarz RL, Blombery P, Karai LJ, Pittaluga S, Jaffe ES, et al. Reactivation of DNA viruses in association with histone deacetylase inhibitor therapy: a case series report. Haematologica. 2009 Nov;94(11):1618–22. PubMed PMID: 19608677. Pubmed Central PMCID: 2770976.Google Scholar
  160. 160.
    Gardner JM, Introcaso CE, Nasta SD, Kim EJ, Vittorio CC, Rook AH. A novel regimen of vorinostat with interferon gamma for refractory Sezary syndrome. J Am Acad Dermatol. 2009 Jul;61(1):112–6. PubMed PMID: 19539845. Epub 2009/06/23. eng.Google Scholar
  161. 161.
    Samimi S, et al. Romidepsin and interferon gamma: a novel combination for refractory cutaneous T-cell lymphoma. J Am Acad Dermatol. 2013;68(1):e5–6.PubMedCrossRefGoogle Scholar
  162. 162.
    Krieg AM. CpG motifs: the active ingredient in bacterial extracts? Nat Med. 2003;9(7):831–5.PubMedCrossRefGoogle Scholar
  163. 163.
    Lonsdorf AS, et al. Intratumor CpG-oligodeoxynucleotide injection induces protective antitumor T cell immunity. J Immunol. 2003;171(8):3941–6.PubMedCrossRefGoogle Scholar
  164. 164.
    Kim YH, et al. Phase I trial of a Toll-like receptor 9 agonist, PF-3512676 (CPG 7909), in patients with treatment-refractory, cutaneous T-cell lymphoma. J Am Acad Dermatol. 2010;63(6):975–83.PubMedCrossRefGoogle Scholar
  165. 165.
    Kim YH, et al. In situ vaccination against mycosis fungoides by intratumoral injection of a TLR9 agonist combined with radiation: a phase 1/2 study. Blood. 2012;119(2):355–63.PubMedPubMedCentralCrossRefGoogle Scholar
  166. 166.
    Tritel M, et al. Prime-boost vaccination with HIV-1 Gag protein and cytosine phosphate guanosine oligodeoxynucleotide, followed by adenovirus, induces sustained and robust humoral and cellular immune responses. J Immunol. 2003;171(5):2538–47.PubMedCrossRefGoogle Scholar
  167. 167.
    Bergstrom RT, et al. CD40 monoclonal antibody activation of antigen-presenting cells improves therapeutic efficacy of tumor-specific T cells. Otolaryngol Head Neck Surg. 2004;130(1):94–103.PubMedCrossRefGoogle Scholar
  168. 168.
    Watanabe S, et al. The duration of signaling through CD40 directs biological ability of dendritic cells to induce antitumor immunity. J Immunol. 2003;171(11):5828–36.PubMedCrossRefGoogle Scholar
  169. 169.
    Rook AH, et al. Interleukin-12 therapy of cutaneous T-cell lymphoma induces lesion regression and cytotoxic T-cell responses. Blood. 1999;94(3):902–8.PubMedGoogle Scholar
  170. 170.
    Duvic M, et al. A phase II open-label study of recombinant human interleukin-12 in patients with stage IA, IB, or IIA mycosis fungoides. J Am Acad Dermatol. 2006;55(5):807–13.PubMedCrossRefGoogle Scholar
  171. 171.
    Zaki MH, et al. Dysregulation of lymphocyte interleukin-12 receptor expression in Sezary syndrome. J Invest Dermatol. 2001;117(1):119–27.PubMedCrossRefGoogle Scholar
  172. 172.
    Berger CL, et al. Tumor-specific peptides in cutaneous T-cell lymphoma: association with class I major histocompatibility complex and possible derivation from the clonotypic T-cell receptor. Int J Cancer. 1998;76(3):304–11.PubMedCrossRefGoogle Scholar
  173. 173.
    Winter D, et al. Definition of TCR epitopes for CTL-mediated attack of cutaneous T cell lymphoma. J Immunol. 2003;171(5):2714–24.PubMedCrossRefGoogle Scholar
  174. 174.
    Muche JM, Sterry W. Vaccination therapy for cutaneous T-cell lymphoma. Clin Exp Dermatol. 2002;27(7):602–7.PubMedCrossRefGoogle Scholar
  175. 175.
    Maier T, et al. Vaccination of patients with cutaneous T-cell lymphoma using intranodal injection of autologous tumor-lysate-pulsed dendritic cells. Blood. 2003;102(7):2338–44.PubMedCrossRefGoogle Scholar
  176. 176.
    Rook AH, et al. The potential therapeutic role of interleukin-12 in cutaneous T-cell lymphoma. Ann N Y Acad Sci. 1996;795:310–8.PubMedCrossRefGoogle Scholar
  177. 177.
    Berard M, et al. IL-15 promotes the survival of naive and memory phenotype CD8+ T cells. J Immunol. 2003;170(10):5018–26.PubMedCrossRefGoogle Scholar
  178. 178.
    Son YI, et al. Interleukin-18 (IL-18) synergizes with IL-2 to enhance cytotoxicity, interferon-gamma production, and expansion of natural killer cells. Cancer Res. 2001;61(3):884–8.PubMedGoogle Scholar
  179. 179.
    Strengell M, et al. IL-21 in synergy with IL-15 or IL-18 enhances IFN-gamma production in human NK and T cells. J Immunol. 2003;170(11):5464–9.PubMedCrossRefGoogle Scholar
  180. 180.
    Miller G, et al. Endogenous granulocyte-macrophage colony-stimulating factor overexpression in vivo results in the long-term recruitment of a distinct dendritic cell population with enhanced immunostimulatory function. J Immunol. 2002;169(6):2875–85.PubMedCrossRefGoogle Scholar
  181. 181.
    Chang DZ, et al. Granulocyte-macrophage colony stimulating factor: an adjuvant for cancer vaccines. Hematology. 2004;9(3):207–15.PubMedCrossRefGoogle Scholar
  182. 182.
    Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000 Oct 2;192(7):1027–34. PubMed PMID: 11015443. Pubmed Central PMCID: 2193311.Google Scholar
  183. 183.
    Sznol M, Chen L. Antagonist antibodies to PD-1 and B7-H1 (PD-L1) in the treatment of advanced human cancer–response. Clin Cancer Res. 2013 Oct 1;19(19):5542. PubMed PMID: 24048329.Google Scholar
  184. 184.
    Kantekure K, Yang Y, Raghunath P, Schaffer A, Woetmann A, Zhang Q, et al. Expression patterns of the immunosuppressive proteins PD-1/CD279 and PD-L1/CD274 at different stages of cutaneous T-cell lymphoma/mycosis fungoides. Am J Dermatopathol. 2012 Feb;34(1):126–8. PubMed PMID: 22094231. Pubmed Central PMCID: 3262090.Google Scholar
  185. 185.
    Samimi S, Benoit B, Evans K, Wherry EJ, Showe L, Wysocka M, et al. Increased programmed death-1 expression on CD4+ T cells in cutaneous T-cell lymphoma: implications for immune suppression. Arch Dermatol. 2010 Dec;146(12):1382–8. PubMed PMID: 20713771. Epub 2010/08/18. eng.Google Scholar
  186. 186.
    Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, et al. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol. 2014 Apr 1;32(10):1020–30. PubMed PMID: 24590637. Pubmed Central PMCID: 4811023.Google Scholar
  187. 187.
    Wu PA, Kim YH, Lavori PW, Hoppe RT, Stockerl-Goldstein KE. A meta-analysis of patients receiving allogeneic or autologous hematopoietic stem cell transplant in mycosis fungoides and Sezary syndrome. Biol Blood Marrow Transplant. 2009 Aug;15(8):982–90. PubMed PMID: 19589488. Epub 2009/07/11. eng.Google Scholar
  188. 188.
    Ishida T, Ueda R. CCR4 as a novel molecular target for immunotherapy of cancer. Cancer Sci. 2006;97(11):1139–46.PubMedCrossRefGoogle Scholar
  189. 189.
    Ishida T, et al. The CC chemokine receptor 4 as a novel specific molecular target for immunotherapy in adult T-Cell leukemia/lymphoma. Clin Cancer Res. 2004;10(22):7529–39.PubMedCrossRefGoogle Scholar
  190. 190.
    Hino R, Shimauchi T, Tokura Y. Treatment with IFN-gamma increases serum levels of Th1 chemokines and decreases those of Th2 chemokines in patients with mycosis fungoides. J Dermatol Sci. 2005;38(3):189–95.PubMedCrossRefGoogle Scholar
  191. 191.
    Richardson SK, et al. Bexarotene blunts malignant T-cell chemotaxis in Sezary syndrome: reduction of chemokine receptor 4 (CCR4)-positive lymphocytes and decreased chemotaxis to thymus and activation regulated chemokine (TARC). Am J Hematol. 2007 (in press).Google Scholar
  192. 192.
    Richardson S, et al. Low-dose bexarotene and low-dose interferon alfa-2b for adult T-cell leukemia/lymphoma associated with human T-lymphotropic virus 1. Arch Dermatol. 2005;141(3):301–4.PubMedCrossRefGoogle Scholar
  193. 193.
    Ahern K, Gilmore ES, Poligone B. Pruritus in cutaneous T-cell lymphoma: a review. J Am Acad Dermatol. 2012;67(4):760–8.PubMedPubMedCentralCrossRefGoogle Scholar
  194. 194.
    Sokolowska-Wojdylo M, et al. Association of distinct IL-31 polymorphisms with pruritus and severity of atopic dermatitis. J Eur Acad Dermatol Venereol. 2013;27(5):662–4.PubMedCrossRefGoogle Scholar
  195. 195.
    Hartmann K, et al. Serum IL-31 levels are increased in a subset of patients with mastocytosis and correlate with disease severity in adult patients. J Allergy Clin Immunol. 2013;132(1):232–5.PubMedCrossRefGoogle Scholar
  196. 196.
    Miyagaki T, et al. Increased CCL18 expression in patients with cutaneous T-cell lymphoma: association with disease severity and prognosis. J Eur Acad Dermatol Venereol. 2013;27(1):e60–7.PubMedCrossRefGoogle Scholar
  197. 197.
    Singer EM, et al. IL-31 is produced by the malignant T-cell population in cutaneous T-Cell lymphoma and correlates with CTCL pruritus. J Invest Dermatol. 2013;133(12):2783–5.PubMedCrossRefGoogle Scholar
  198. 198.
    Horwitz SM, et al. Review of the treatment of mycosis fungoides and Sezary syndrome: a stage-based approach. J Natl Compr Canc Netw. 2008;6(4):436–42.PubMedGoogle Scholar
  199. 199.
    Oyama Y, et al. High-dose therapy and bone marrow transplantation in cutaneous T-cell lymphoma. Hematol Oncol Clin North Am. 2003;17(6):1475–83, xi.PubMedCrossRefGoogle Scholar
  200. 200.
    Storb R, et al. Allogeneic hematopoietic stem cell transplantation: from the nuclear age into the twenty-first century. Transplant Proc. 2000;32(7):2548–9.PubMedCrossRefGoogle Scholar
  201. 201.
    Baron F, Sandmaier BM. Current status of hematopoietic stem cell transplantation after nonmyeloablative conditioning. Curr Opin Hematol. 2005;12(6):435–43.PubMedCrossRefGoogle Scholar
  202. 202.
    Bigler RD, et al. Autologous bone marrow transplantation for advanced stage mycosis fungoides. Bone Marrow Transplant. 1991;7(2):133–7.PubMedGoogle Scholar
  203. 203.
    Olavarria E, et al. T-cell depletion and autologous stem cell transplantation in the management of tumour stage mycosis fungoides with peripheral blood involvement. Br J Haematol. 2001;114(3):624–31.PubMedCrossRefGoogle Scholar
  204. 204.
    Burt RK, et al. Allogeneic hematopoietic stem cell transplantation for advanced mycosis fungoides: evidence of a graft-versus-tumor effect. Bone Marrow Transplant. 2000;25(1):111–3.PubMedCrossRefGoogle Scholar
  205. 205.
    Masood N, et al. Induction of complete remission of advanced stage mycosis fungoides by allogeneic hematopoietic stem cell transplantation. J Am Acad Dermatol. 2002;47(1):140–5.PubMedCrossRefGoogle Scholar
  206. 206.
    Soligo D, et al. Treatment of advanced mycosis fungoides by allogeneic stem-cell transplantation with a nonmyeloablative regimen. Bone Marrow Transplant. 2003;31(8):663–6.PubMedCrossRefGoogle Scholar
  207. 207.
    Guitart J, et al. Long-term remission after allogeneic hematopoietic stem cell transplantation for refractory cutaneous T-cell lymphoma. Arch Dermatol. 2002;138(10):1359–65.PubMedCrossRefGoogle Scholar
  208. 208.
    Molina A, et al. Durable clinical, cytogenetic, and molecular remissions after allogeneic hematopoietic cell transplantation for refractory Sezary syndrome and mycosis fungoides. J Clin Oncol. 2005;23(25):6163–71.PubMedCrossRefGoogle Scholar
  209. 209.
    Fijnheer R, et al. Complete remission of a radiochemotherapy-resistant cutaneous T-cell lymphoma with allogeneic non-myeloablative stem cell transplantation. Bone Marrow Transplant. 2003;32(3):345–7.PubMedCrossRefGoogle Scholar
  210. 210.
    Wu PA, et al. A meta-analysis of patients receiving allogeneic or autologous hematopoietic stem cell transplant in mycosis fungoides and Sezary syndrome. (1523–6536 (Electronic)).Google Scholar
  211. 211.
    Duarte RF, Canals C, Onida F, Gabriel IH, Arranz R, Arcese W, et al. Allogeneic hematopoietic cell transplantation for patients with mycosis fungoides and Sezary syndrome: a retrospective analysis of the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol. 2010 Oct 10;28(29):4492–9. PubMed PMID: 20697072. Epub 2010/08/11. eng.Google Scholar
  212. 212.
    Duvic M, Donato M, Dabaja B, Richmond H, Singh L, Wei W, et al. Total skin electron beam and non-myeloablative allogeneic hematopoietic stem-cell transplantation in advanced mycosis fungoides and Sezary syndrome. J Clin Oncol. 2010 May 10;28(14):2365–72. PubMed PMID: 20351328. Epub 2010/03/31. eng.Google Scholar
  213. 213.
    Jawed SI, Myskowski PL, Horwitz S, Moskowitz A, Querfeld C. Primary cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome): part II. Prognosis, management, and future directions. J Am Acad Dermatol. 2014 Feb;70(2):223 e1–17; quiz 40–2. PubMed PMID: 24438970. Epub 2014/01/21. eng.Google Scholar

Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  • Sasha Stephen
    • 1
  • Ellen J. Kim
    • 2
  • Camille E. Introcaso
    • 3
  • Stephen K. Richardson
    • 4
  • Alain H. Rook
    • 5
  1. 1.Department of DermatologyChildren’s Hospital of PhiladelphiaPhiladelphiaUSA
  2. 2.Department of DermatologyHospital of the University of PennsylvaniaPhiladelphiaUSA
  3. 3.Department of DermatologyPennsylvania Centre DermatologyPhiladelphiaUSA
  4. 4.Department of DermatologyTallahassee Memorial Healthcare Hospital, Dermatology Associates of TallahasseeTallahasseeUSA
  5. 5.Department of DermatologyPerelman School of Medicine at the University of PennsylvaniaPhiladelphiaUSA

Personalised recommendations