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Mycosis Fungoides (Including SÚzary Syndrome) Treatment (PDQ«)

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General Information About Mycosis Fungoides (Including SÚzary Syndrome)
Cellular Classification of Mycosis Fungoides (Including SÚzary Syndrome)
Stage Information for Mycosis Fungoides (Including SÚzary Syndrome)
Treatment Option Overview for Mycosis Fungoides (Including SÚzary Syndrome)
Stage I and Stage II Mycosis Fungoides Treatment
Stage III and Stage IV Mycosis Fungoides (Including SÚzary Syndrome) Treatment
Recurrent Mycosis Fungoides (Including SÚzary Syndrome) Treatment
Key References for Mycosis Fungoides (Including SÚzary Syndrome)
Changes to This Summary (05/04/2018)
About This PDQ Summary

General Information About Mycosis Fungoides (Including SÚzary Syndrome)

Clinical Presentation

Mycosis fungoides and SÚzary syndrome are neoplasias of malignant T lymphocytes that usually possess the helper/inducer cell surface phenotype. These kinds of neoplasms initially present as skin involvement and, as such, have been classified as cutaneous T-cell lymphomas. [1] Cutaneous T-cell lymphomas should be distinguished from other T-cell lymphomas that involve the skin, such as anaplastic large cell lymphoma (CD30 positive), peripheral T-cell lymphoma (CD30 negative, with no epidermal involvement), adult T-cell leukemia/lymphoma (usually with systemic involvement), or subcutaneous panniculitic T-cell lymphoma. [2] [3] These histologic types of T-cell lymphomas are discussed in another PDQ summary. (Refer to the PDQ summary on Adult Non-Hodgkin Lymphoma Treatment for more information.)

Typically, the natural history of mycosis fungoides is indolent. [4] Symptoms of the disease may present for long periods, in a range of 2 to 10 years, because cutaneous eruptions wax and wane before they receive a biopsy confirmation. Mycosis fungoides and SÚzary syndrome are treatable with available topical therapy, systemic therapy, or both. To date, curative modalities have proven elusive with the possible exception of patients with minimal disease confined to the skin.

In addition, a number of benign or indolent conditions can be confused with mycosis fungoides. Consultation with a pathologist who has expertise in distinguishing these conditions is important. [1]

Prognosis and Survival

The prognosis of patients with mycosis fungoides and SÚzary syndrome is based on the extent of disease (stage) at presentation. [5] The presence of lymphadenopathy and involvement of peripheral blood and viscera increase in likelihood with worsening cutaneous involvement and define poor prognostic groups. [5] [6] [7] [8] The Cutaneous Lymphoma International Consortium retrospectively reviewed 1,275 patients and found the following four independent prognostic markers indicate a worse survival: [9]

The median survival following diagnosis varies according to stage. Patients with stage IA disease have a median survival of 20 years or more. Most deaths for this group are not caused by, nor are they related to, mycosis fungoides. [10] [11] In contrast, more than 50% of patients with stage III through stage IV disease die of mycosis fungoides, with a median survival of approximately 5 years. [7] [9] [12] [13] The Cutaneous Lymphoma International Prognostic index used male gender, age older than 60 years, plaques, lymph nodes, blood involvement, and visceral involvement as poor prognostic factors to define predicted overall survival (OS) and progression-free survival in both early-stage and advanced-stage groups. [14]

A report on 1,798 patients from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program database found an increase in second malignancies (standardized incidence ratio, 1.32; 95% confidence interval [CI], 1.15–1.52), especially for Hodgkin lymphoma, non-Hodgkin lymphoma, and myeloma. [15] Another report on 4,459 patients from the SEER database found that the 19.2% of African Americans with mycosis fungoides have a shorter OS, potentially attributable to disease characteristics, socioeconomic status, and type of therapy (hazard ratio, 1.47; 95% CI, 1.25–1.74; P < .001). [16]

Cutaneous disease can manifest itself as an eczematous patch or plaque stage covering less than 10% of the body surface (T1), a plaque stage covering 10% or more of the body surface (T2), or as tumors (T3) that frequently undergo necrotic ulceration. [17] [18] Several retrospective studies showed that 20% of patients progress from stage I or II disease to stage III or IV disease. [19] [20] [21] SÚzary syndrome presents with generalized erythroderma (T4) and peripheral blood involvement. However, there is some disagreement about whether mycosis fungoides and SÚzary syndrome are actually variants of the same disease. [22] The same retrospective study with a median follow-up of 14.5 years found that only 3% of 1,422 patients progressed from mycosis fungoides to SÚzary syndrome. [19]

There is consensus that patients with SÚzary syndrome (leukemic involvement) have a poor prognosis (median survival, 4 years), with or without the typical generalized erythroderma. [23] [24] Cytologic transformation from a low-grade lymphoma to a high-grade lymphoma (large cell transformation) occurs rarely (<5%) during the course of these diseases and is associated with a poor prognosis. [25] [26] [27] A retrospective analysis of 100 cases with large cell transformation found reduced disease-specific survival with extracutaneous transformation, increased extent of skin lesions, and CD30 negativity. [28] A common cause of death during the tumor phase is sepsis from Pseudomonas aeruginosa or Staphylococcus aureus caused by chronic skin infection with staph species and subsequent systemic infections. [18]

Folliculotropic mycosis fungoides is a variant of mycosis fungoides marked by folliculotropic, rather than epidermotropic, neoplastic infiltrates, with preferential location in the head and neck area. [29] Early plaque-stage folliculotropic mycosis fungoides have a very indolent prognosis, while extracutaneous disease portends a very poor prognosis. [29]

References:

  1. Wilcox RA: Cutaneous T-cell lymphoma: 2017 update on diagnosis, risk-stratification, and management. Am J Hematol 92 (10): 1085-1102, 2017.
  2. Willemze R, Kerl H, Sterry W, et al.: EORTC classification for primary cutaneous lymphomas: a proposal from the Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer. Blood 90 (1): 354-71, 1997.
  3. Harris NL, Jaffe ES, Stein H, et al.: A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 84 (5): 1361-92, 1994.
  4. Diamandidou E, Cohen PR, Kurzrock R: Mycosis fungoides and Sezary syndrome. Blood 88 (7): 2385-409, 1996.
  5. Agar NS, Wedgeworth E, Crichton S, et al.: Survival outcomes and prognostic factors in mycosis fungoides/SÚzary syndrome: validation of the revised International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer staging proposal. J Clin Oncol 28 (31): 4730-9, 2010.
  6. Talpur R, Singh L, Daulat S, et al.: Long-term outcomes of 1,263 patients with mycosis fungoides and SÚzary syndrome from 1982 to 2009. Clin Cancer Res 18 (18): 5051-60, 2012.
  7. Kim YH, Liu HL, Mraz-Gernhard S, et al.: Long-term outcome of 525 patients with mycosis fungoides and Sezary syndrome: clinical prognostic factors and risk for disease progression. Arch Dermatol 139 (7): 857-66, 2003.
  8. Alberti-Violetti S, Talpur R, Schlichte M, et al.: Advanced-stage mycosis fungoides and SÚzary syndrome: survival and response to treatment. Clin Lymphoma Myeloma Leuk 15 (6): e105-12, 2015.
  9. Scarisbrick JJ, Prince HM, Vermeer MH, et al.: Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and SÚzary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model. J Clin Oncol 33 (32): 3766-73, 2015.
  10. Kim YH, Jensen RA, Watanabe GL, et al.: Clinical stage IA (limited patch and plaque) mycosis fungoides. A long-term outcome analysis. Arch Dermatol 132 (11): 1309-13, 1996.
  11. Vollmer RT: A review of survival in mycosis fungoides. Am J Clin Pathol 141 (5): 706-11, 2014.
  12. Zackheim HS, Amin S, Kashani-Sabet M, et al.: Prognosis in cutaneous T-cell lymphoma by skin stage: long-term survival in 489 patients. J Am Acad Dermatol 40 (3): 418-25, 1999.
  13. de Coninck EC, Kim YH, Varghese A, et al.: Clinical characteristics and outcome of patients with extracutaneous mycosis fungoides. J Clin Oncol 19 (3): 779-84, 2001.
  14. Benton EC, Crichton S, Talpur R, et al.: A cutaneous lymphoma international prognostic index (CLIPi) for mycosis fungoides and Sezary syndrome. Eur J Cancer 49 (13): 2859-68, 2013.
  15. Huang KP, Weinstock MA, Clarke CA, 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 143 (1): 45-50, 2007.
  16. Su C, Nguyen KA, Bai HX, et al.: Racial disparity in mycosis fungoides: An analysis of 4495 cases from the US National Cancer Database. J Am Acad Dermatol 77 (3): 497-502.e2, 2017.
  17. Siegel RS, Pandolfino T, Guitart J, et al.: Primary cutaneous T-cell lymphoma: review and current concepts. J Clin Oncol 18 (15): 2908-25, 2000.
  18. Lorincz AL: Cutaneous T-cell lymphoma (mycosis fungoides) Lancet 347 (9005): 871-6, 1996.
  19. Quaglino P, Pimpinelli N, Berti E, et al.: Time course, clinical pathways, and long-term hazards risk trends of disease progression in patients with classic mycosis fungoides: a multicenter, retrospective follow-up study from the Italian Group of Cutaneous Lymphomas. Cancer 118 (23): 5830-9, 2012.
  20. Wernham AG, Shah F, Amel-Kashipaz R, et al.: Stage I mycosis fungoides: frequent association with a favourable prognosis but disease progression and disease-specific mortality may occur. Br J Dermatol 173 (5): 1295-7, 2015.
  21. Desai M, Liu S, Parker S: Clinical characteristics, prognostic factors, and survival of 393 patients with mycosis fungoides and SÚzary syndrome in the southeastern United States: a single-institution cohort. J Am Acad Dermatol 72 (2): 276-85, 2015.
  22. Olsen EA, Rook AH, Zic J, et al.: SÚzary syndrome: immunopathogenesis, literature review of therapeutic options, and recommendations for therapy by the United States Cutaneous Lymphoma Consortium (USCLC). J Am Acad Dermatol 64 (2): 352-404, 2011.
  23. Kubica AW, Davis MD, Weaver AL, et al.: SÚzary syndrome: a study of 176 patients at Mayo Clinic. J Am Acad Dermatol 67 (6): 1189-99, 2012.
  24. Thompson AK, Killian JM, Weaver AL, et al.: SÚzary syndrome without erythroderma: A review of 16 cases at Mayo Clinic. J Am Acad Dermatol 76 (4): 683-688, 2017.
  25. Kim YH, Bishop K, Varghese A, et al.: Prognostic factors in erythrodermic mycosis fungoides and the SÚzary syndrome. Arch Dermatol 131 (9): 1003-8, 1995.
  26. Arulogun SO, Prince HM, Ng J, et al.: Long-term outcomes of patients with advanced-stage cutaneous T-cell lymphoma and large cell transformation. Blood 112 (8): 3082-7, 2008.
  27. Kadin ME, Hughey LC, Wood GS: Large-cell transformation of mycosis fungoides-differential diagnosis with implications for clinical management: a consensus statement of the US Cutaneous Lymphoma Consortium. J Am Acad Dermatol 70 (2): 374-6, 2014.
  28. Benner MF, Jansen PM, Vermeer MH, et al.: Prognostic factors in transformed mycosis fungoides: a retrospective analysis of 100 cases. Blood 119 (7): 1643-9, 2012.
  29. van Santen S, Roach RE, van Doorn R, et al.: Clinical Staging and Prognostic Factors in Folliculotropic Mycosis Fungoides. JAMA Dermatol 152 (9): 992-1000, 2016.

Cellular Classification of Mycosis Fungoides (Including SÚzary Syndrome)

The histologic diagnosis of mycosis fungoides and SÚzary syndrome is usually difficult to determine in the initial stages of the disease and may require the review of multiple biopsies by an experienced pathologist.

A definitive diagnosis from a skin biopsy requires the presence of mycosis fungoides and SÚzary syndrome cells (convoluted lymphocytes), a band-like upper dermal infiltrate, and epidermal infiltrations with Pautrier abscesses (collections of neoplastic lymphocytes). A definitive diagnosis of SÚzary syndrome may be made from a peripheral blood evaluation when skin biopsies are consistent with the diagnosis. Supportive evidence for circulating SÚzary cells is provided by T-cell receptor gene analysis, identification of the atypical lymphocytes with hyperconvoluted or cerebriform nuclei, and flow cytometry with the characteristic deletion of cell surface markers such as CD7 and CD26. However, none of these is individually pathognomonic for lymphoma. [1] [2]

References:

  1. Olsen EA, Rook AH, Zic J, et al.: SÚzary syndrome: immunopathogenesis, literature review of therapeutic options, and recommendations for therapy by the United States Cutaneous Lymphoma Consortium (USCLC). J Am Acad Dermatol 64 (2): 352-404, 2011.
  2. Fraser-Andrews EA, Russell-Jones R, Woolford AJ, et al.: Diagnostic and prognostic importance of T-cell receptor gene analysis in patients with SÚzary syndrome. Cancer 92 (7): 1745-52, 2001.

Stage Information for Mycosis Fungoides (Including SÚzary Syndrome)

Note: The American Joint Committee on Cancer (AJCC) has published the 8th edition of the AJCC Cancer Staging Manual, which includes revisions to the staging for this disease. Implementation of the 8th edition began in January 2018. The PDQ Adult Treatment Editorial Board, which maintains this summary, is reviewing the revised staging and will make appropriate changes as needed.

The stages that follow are defined by TNM classification (tumor, node, metastasis). Peripheral blood involvement with mycosis fungoides or SÚzary syndrome cells is correlated with more advanced skin stage, lymph node and visceral involvement, and shortened survival.

Mycosis fungoides and SÚzary syndrome have a formal staging system proposed by the International Society for Cutaneous Lymphomas (ISCL) and the European Organization of Research and Treatment of Cancer (EORTC). [1] [2]

Definitions of TNM

The AJCC has designated staging by TNM classification to define mycosis fungoides. [3]

Table 1. ISCL/EORTC Revision to the Classification of Mycosis Fungoides and SÚzary Syndromea

Skin
T1Limited patchesb, papules, and/or plaquesc covering <10% of the skin surface. May further stratify into T1a (patch only) vs. T1b (plaque ▒ patch).
T2Patches, papules, or plaques covering ≥10% of the skin surface. May further stratify into T2a (patch only) vs. T2b (plaque ▒ patch).
T3≥1 tumord (≥1 cm diameter).
T4Confluence of erythema covering ≥80% of body surface area.
Node
N0No clinically abnormal peripheral lymph nodese; biopsy not required.
N1Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 1 or NCI LN0–2.
N1aClone negativef.
N1bClone positivef.
N2Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 2 or NCI LN3.
N2aClone negativef.
N2bClone positivef.
N3Clinically abnormal peripheral lymph nodes; histopathology Dutch grades 3–4 or NCI LN4; clone positive or negative.
NxClinically abnormal peripheral lymph nodes; no histologic confirmation.
Visceral
M0No visceral organ involvement.
M1Visceral involvement (must have pathology confirmationg, and organ involved should be specified).
Peripheral Blood Involvement
B0Absence of significant blood involvement: ≤5% of peripheral blood lymphocytes are atypical (SÚzary) cellsh.
B0aClone negativef.
B0bClone positivef.
B1Low blood-tumor burden: >5% of peripheral blood lymphocytes are atypical (SÚzary) cells but does not meet the criteria of B2.
B1aClone negativef.
B1bClone positivef.
B2High blood-tumor burden: ≥1,000/μL SÚzary cellsh with positive clonef.
EORTC = European Organization of Research and Treatment of Cancer; ISCL = International Society for Cutaneous Lymphomas; LN = lymph nodes; NCI = National Cancer Institute.
aReprinted with permission from AJCC: Primary cutaneous lymphomas. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, p 613-5.
bFor skin, patch indicates any size skin lesion without significant elevation or induration. Presence/absence of hypo- or hyperpigmentation, scale, crusting, and/or poikiloderma should be noted.
cFor skin, plaque indicates any size skin lesion that is elevated or indurated. Presence or absence of scale, crusting, and/or poikiloderma should be noted. Histologic features such as folliculotropism or large-cell transformation (>25% large cells), CD30+ or CD30-, and clinical features, such as ulceration, are important to document.
dFor skin, tumor indicates at least 1 cm diameter solid or nodular lesion with evidence of depth and/or vertical growth. Note total number of lesions, total volume of lesions, largest size lesion, and region of body involved. Also, note if histologic evidence of large cell transformation has occurred. Phenotyping for CD30 is encouraged.
eFor node, abnormal peripheral lymph node(s) indicates any palpable peripheral node that on physical examination is firm, irregular, clustered, fixed, or ≥1.5 cm in diameter. Node groups examined on physical examination include: cervical, supraclavicular, epitrochlear, axillary, and inguinal. Central nodes, which are not generally amenable to pathologic assessment, are not currently considered in the nodal classification unless used to establish N3 histopathologically.
fA T-cell clone is defined by polymerase chain reaction or Southern blot analysis of the T-cell receptor (TCR) gene.
gFor viscera, spleen and liver may be diagnosed by imaging criteria.
hFor blood, SÚzary cells are defined as lymphocytes with hyperconvoluted cerebriform nuclei. If SÚzary cells are not able to be used to determine tumor burden for B2, then one of the following modified ISCL criteria along with a positive clonal rearrangement of the TCR may be used instead: (1) expanded CD4+ or CD3+ cells with CD4/CD8 ratio of ≥10; and (2) expanded CD4+ cells with abnormal immunophenotype, including loss of CD7 or CD26.

Table 2. Anatomic Stage/Prognostic Groupsa,b

ISCL/EORTC Revision to the Staging of Mycosis Fungoides (Including SÚzary Syndrome)
StageTNMPeripheral Blood Involvement
IA1000, 1
IB2000, 1
IIA1, 21, 200, 1
IIB30–200, 1
III40–200, 1
IIIA40–200
IIIB40–201
IVA11–40–202
IVA21–4300–2
IVB1–40–310–2
EORTC = European Organization of Research and Treatment of Cancer; ISCL = International Society for Cutaneous Lymphomas; M = distant metastasis; N = regional lymph nodes; T = primary tumor.
aReprinted with permission from AJCC: Primary cutaneous lymphomas. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, p 613-5.
bAdapted from Olsen et al. [1]

Clinical trials have assessed the extent of skin involvement using detailed scoring systems such as the modified Severity-Weighted Assessment Tool (mSWAT). [4]

References:

  1. Olsen E, Vonderheid E, Pimpinelli N, et al.: Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC). Blood 110 (6): 1713-22, 2007.
  2. Agar NS, Wedgeworth E, Crichton S, et al.: Survival outcomes and prognostic factors in mycosis fungoides/SÚzary syndrome: validation of the revised International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer staging proposal. J Clin Oncol 28 (31): 4730-9, 2010.
  3. Primary cutaneous lymphomas. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 614-5.
  4. Olsen EA, Whittaker S, Kim YH, et al.: Clinical end points and response criteria in mycosis fungoides and SÚzary syndrome: a consensus statement of the International Society for Cutaneous Lymphomas, the United States Cutaneous Lymphoma Consortium, and the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer. J Clin Oncol 29 (18): 2598-607, 2011.

Treatment Option Overview for Mycosis Fungoides (Including SÚzary Syndrome)

Treatment options for patients with mycosis fungoides and SÚzary syndrome include the following: [1] [2]

Photodynamic Therapy

  1. Psoralen and ultraviolet A radiation (PUVA).
  2. Extracorporeal photochemotherapy alone [8] [9] [10] or in combination with total-skin electron-beam radiation (TSEB). [11]

Radiation Therapy

  1. TSEB.
  2. Ultraviolet B radiation (UVB) or ultraviolet A radiation (UVA). [3] [18]
  3. Local electron-beam radiation or orthovoltage radiation therapy may be used to palliate areas of bulky or symptomatic skin disease. [19]

Biologic Therapy

  1. Interferon alpha or interferon gamma alone or in combination with topical therapy. [20] [21]

Chemotherapy

  1. Topical chemotherapy with mechlorethamine (nitrogen mustard).
  2. Oral methotrexate (NCT00425555). [25]
  3. Pegylated liposomal doxorubicin. [26] [27] [28]
  4. Fludarabine, 2-chlorodeoxyadenosine, and pentostatin are active agents for mycosis fungoides and SÚzary syndrome. [21] [29] [30] [31]
  5. Single-agent chemotherapy or combination systemic chemotherapy (chlorambucil plus prednisone, mechlorethamine, cyclophosphamide, methotrexate, and combination chemotherapy) are often combined with treatment directed at the skin. [22] [32] [33] [34]
  6. Pralatrexate (folate analog). [35] [36]

Other Drug Therapy

  1. Symptomatic management with topical corticosteroids.
  2. Bexarotene, an oral or topical retinoid (NCT00255801). [37] [38]
  3. Lenalidomide. [39]
  4. Vorinostat or romidepsin or other histone deacetylase inhibitors (HDACi). [1] [40] [41] [42]

Targeted Therapy

  1. Brentuximab vedotin. [43] [44]

Transplantation

  1. Allogeneic or autologous bone marrow transplantation. [45] [46] [47] [47] [48]

These types of treatments produce remissions, but long-term remissions are uncommon. Treatment, therefore, is considered palliative for most patients, although major symptomatic improvement is regularly achieved. Survival in excess of 8 years, however, is common for patients with early stages of disease. All patients with mycosis fungoides and SÚzary syndrome are candidates for clinical trials evaluating new approaches to treatment.

References:

  1. Olsen EA, Rook AH, Zic J, et al.: SÚzary syndrome: immunopathogenesis, literature review of therapeutic options, and recommendations for therapy by the United States Cutaneous Lymphoma Consortium (USCLC). J Am Acad Dermatol 64 (2): 352-404, 2011.
  2. Trautinger F, Eder J, Assaf C, et al.: European Organisation for Research and Treatment of Cancer consensus recommendations for the treatment of mycosis fungoides/SÚzary syndrome - Update 2017. Eur J Cancer 77: 57-74, 2017.
  3. Olsen EA, Hodak E, Anderson T, et al.: Guidelines for phototherapy of mycosis fungoides and SÚzary syndrome: A consensus statement of the United States Cutaneous Lymphoma Consortium. J Am Acad Dermatol 74 (1): 27-58, 2016.
  4. Herrmann JJ, Roenigk HH Jr, Hurria A, et al.: Treatment of mycosis fungoides with photochemotherapy (PUVA): long-term follow-up. J Am Acad Dermatol 33 (2 Pt 1): 234-42, 1995.
  5. Ramsay DL, Lish KM, Yalowitz CB, et al.: Ultraviolet-B phototherapy for early-stage cutaneous T-cell lymphoma. Arch Dermatol 128 (7): 931-3, 1992.
  6. Querfeld C, Rosen ST, Kuzel TM, 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 141 (3): 305-11, 2005.
  7. Kuzel TM, Roenigk HH Jr, Samuelson E, et al.: Effectiveness of interferon alfa-2a combined with phototherapy for mycosis fungoides and the SÚzary syndrome. J Clin Oncol 13 (1): 257-63, 1995.
  8. Edelson R, Berger C, Gasparro F, et al.: Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy. Preliminary results. N Engl J Med 316 (6): 297-303, 1987.
  9. Heald PW, Perez MI, McKiernan G, et al.: Extracorporeal photochemotherapy for CTCL. Prog Clin Biol Res 337: 443-7, 1990.
  10. Scarisbrick JJ, Taylor P, Holtick U, et al.: U.K. consensus statement on the use of extracorporeal photopheresis for treatment of cutaneous T-cell lymphoma and chronic graft-versus-host disease. Br J Dermatol 158 (4): 659-78, 2008.
  11. Palareti G, Maccaferri M, Manotti C, et al.: Fibrinogen assays: a collaborative study of six different methods. C.I.S.M.E.L. Comitato Italiano per la Standardizzazione dei Metodi in Ematologia e Laboratorio. Clin Chem 37 (5): 714-9, 1991.
  12. Chinn DM, Chow S, Kim YH, et al.: Total skin electron beam therapy with or without adjuvant topical nitrogen mustard or nitrogen mustard alone as initial treatment of T2 and T3 mycosis fungoides. Int J Radiat Oncol Biol Phys 43 (5): 951-8, 1999.
  13. Quirˇs PA, Jones GW, Kacinski BM, et al.: Total skin electron beam therapy followed by adjuvant psoralen/ultraviolet-A light in the management of patients with T1 and T2 cutaneous T-cell lymphoma (mycosis fungoides). Int J Radiat Oncol Biol Phys 38 (5): 1027-35, 1997.
  14. Ysebaert L, Truc G, Dalac S, et al.: Ultimate results of radiation therapy for T1-T2 mycosis fungoides (including reirradiation). Int J Radiat Oncol Biol Phys 58 (4): 1128-34, 2004.
  15. Jones GW, Rosenthal D, Wilson LD: Total skin electron radiation for patients with erythrodermic cutaneous T-cell lymphoma (mycosis fungoides and the SÚzary syndrome). Cancer 85 (9): 1985-95, 1999.
  16. Navi D, Riaz N, Levin YS, et al.: The Stanford University experience with conventional-dose, total skin electron-beam therapy in the treatment of generalized patch or plaque (T2) and tumor (T3) mycosis fungoides. Arch Dermatol 147 (5): 561-7, 2011.
  17. Micaily B, Miyamoto C, Kantor G, et al.: Radiotherapy for unilesional mycosis fungoides. Int J Radiat Oncol Biol Phys 42 (2): 361-4, 1998.
  18. Elcin G, Duman N, Karahan S, et al.: Long-term follow-up of early mycosis fungoides patients treated with narrowband ultraviolet B phototherapy. J Dermatolog Treat 25 (3): 268-73, 2014.
  19. Thomas TO, Agrawal P, Guitart J, et al.: Outcome of patients treated with a single-fraction dose of palliative radiation for cutaneous T-cell lymphoma. Int J Radiat Oncol Biol Phys 85 (3): 747-53, 2013.
  20. Olsen EA, Bunn PA: Interferon in the treatment of cutaneous T-cell lymphoma. Hematol Oncol Clin North Am 9 (5): 1089-107, 1995.
  21. Foss FM, Ihde DC, Breneman DL, et al.: Phase II study of pentostatin and intermittent high-dose recombinant interferon alfa-2a in advanced mycosis fungoides/SÚzary syndrome. J Clin Oncol 10 (12): 1907-13, 1992.
  22. Hughes CF, Khot A, McCormack C, et al.: Lack of durable disease control with chemotherapy for mycosis fungoides and SÚzary syndrome: a comparative study of systemic therapy. Blood 125 (1): 71-81, 2015.
  23. Lessin SR, Duvic M, Guitart J, et al.: Topical chemotherapy in cutaneous T-cell lymphoma: positive results of a randomized, controlled, multicenter trial testing the efficacy and safety of a novel mechlorethamine, 0.02%, gel in mycosis fungoides. JAMA Dermatol 149 (1): 25-32, 2013.
  24. de Quatrebarbes J, EstŔve E, Bagot M, et al.: Treatment of early-stage mycosis fungoides with twice-weekly applications of mechlorethamine and topical corticosteroids: a prospective study. Arch Dermatol 141 (9): 1117-20, 2005.
  25. Zackheim HS, Kashani-Sabet M, McMillan A: Low-dose methotrexate to treat mycosis fungoides: a retrospective study in 69 patients. J Am Acad Dermatol 49 (5): 873-8, 2003.
  26. Wollina U, Dummer R, Brockmeyer NH, et al.: Multicenter study of pegylated liposomal doxorubicin in patients with cutaneous T-cell lymphoma. Cancer 98 (5): 993-1001, 2003.
  27. Dummer R, Quaglino P, Becker JC, et al.: Prospective international multicenter phase II trial of intravenous pegylated liposomal doxorubicin monochemotherapy in patients with stage IIB, IVA, or IVB advanced mycosis fungoides: final results from EORTC 21012. J Clin Oncol 30 (33): 4091-7, 2012.
  28. Quereux G, Marques S, Nguyen JM, et al.: Prospective multicenter study of pegylated liposomal doxorubicin treatment in patients with advanced or refractory mycosis fungoides or SÚzary syndrome. Arch Dermatol 144 (6): 727-33, 2008.
  29. Saven A, Carrera CJ, Carson DA, et al.: 2-Chlorodeoxyadenosine: an active agent in the treatment of cutaneous T-cell lymphoma. Blood 80 (3): 587-92, 1992.
  30. Foss FM, Ihde DC, Linnoila IR, et al.: Phase II trial of fludarabine phosphate and interferon alfa-2a in advanced mycosis fungoides/SÚzary syndrome. J Clin Oncol 12 (10): 2051-9, 1994.
  31. Kurzrock R, Pilat S, Duvic M: Pentostatin therapy of T-cell lymphomas with cutaneous manifestations. J Clin Oncol 17 (10): 3117-21, 1999.
  32. Kaye FJ, Bunn PA Jr, Steinberg SM, 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 321 (26): 1784-90, 1989.
  33. Rosen ST, Foss FM: Chemotherapy for mycosis fungoides and the SÚzary syndrome. Hematol Oncol Clin North Am 9 (5): 1109-16, 1995.
  34. Zackheim HS, Epstein EH Jr: Low-dose methotrexate for the SÚzary syndrome. J Am Acad Dermatol 21 (4 Pt 1): 757-62, 1989.
  35. Horwitz SM, Kim YH, Foss F, et al.: Identification of an active, well-tolerated dose of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma. Blood 119 (18): 4115-22, 2012.
  36. Talpur R, Thompson A, Gangar P, et al.: Pralatrexate alone or in combination with bexarotene: long-term tolerability in relapsed/refractory mycosis fungoides. Clin Lymphoma Myeloma Leuk 14 (4): 297-304, 2014.
  37. Duvic M, Hymes K, Heald P, 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 19 (9): 2456-71, 2001.
  38. Heald P, Mehlmauer M, Martin AG, et al.: Topical bexarotene therapy for patients with refractory or persistent early-stage cutaneous T-cell lymphoma: results of the phase III clinical trial. J Am Acad Dermatol 49 (5): 801-15, 2003.
  39. Querfeld C, Rosen ST, Guitart J, et al.: Results of an open-label multicenter phase 2 trial of lenalidomide monotherapy in refractory mycosis fungoides and SÚzary syndrome. Blood 123 (8): 1159-66, 2014.
  40. Duvic M, Dummer R, Becker JC, et al.: Panobinostat activity in both bexarotene-exposed and -na´ve patients with refractory cutaneous T-cell lymphoma: results of a phase II trial. Eur J Cancer 49 (2): 386-94, 2013.
  41. Olsen EA, Kim YH, Kuzel TM, et al.: Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma. J Clin Oncol 25 (21): 3109-15, 2007.
  42. Piekarz RL, Frye R, Turner M, et al.: Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma. J Clin Oncol 27 (32): 5410-7, 2009.
  43. Kim YH, Tavallaee M, Sundram U, et al.: Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides and SÚzary Syndrome With Variable CD30 Expression Level: A Multi-Institution Collaborative Project. J Clin Oncol 33 (32): 3750-8, 2015.
  44. Duvic M, Tetzlaff MT, Gangar P, et al.: Results of a Phase II Trial of Brentuximab Vedotin for CD30+ Cutaneous T-Cell Lymphoma and Lymphomatoid Papulosis. J Clin Oncol 33 (32): 3759-65, 2015.
  45. Molina A, Zain J, Arber DA, et al.: Durable clinical, cytogenetic, and molecular remissions after allogeneic hematopoietic cell transplantation for refractory Sezary syndrome and mycosis fungoides. J Clin Oncol 23 (25): 6163-71, 2005.
  46. Duvic M, Donato M, Dabaja B, et al.: Total skin electron beam and non-myeloablative allogeneic hematopoietic stem-cell transplantation in advanced mycosis fungoides and Sezary syndrome. J Clin Oncol 28 (14): 2365-72, 2010.
  47. Duarte RF, Boumendil A, Onida F, et al.: Long-term outcome of allogeneic hematopoietic cell transplantation for patients with mycosis fungoides and SÚzary syndrome: a European society for blood and marrow transplantation lymphoma working party extended analysis. J Clin Oncol 32 (29): 3347-8, 2014.
  48. Schlaak M, Pickenhain J, Theurich S, et al.: Allogeneic stem cell transplantation versus conventional therapy for advanced primary cutaneous T-cell lymphoma. Cochrane Database Syst Rev 1: CD008908, 2012.
  49. Lechowicz MJ, Lazarus HM, Carreras J, et al.: Allogeneic hematopoietic cell transplantation for mycosis fungoides and Sezary syndrome. Bone Marrow Transplant 49 (11): 1360-5, 2014.

Stage I and Stage II Mycosis Fungoides Treatment

Because several forms of treatment can produce complete resolution of skin lesions in this stage, the choice of therapy is dependent on local expertise and the facilities available. With therapy, the survival of patients with stage IA disease can be expected to be the same as for age- and gender-matched controls. [1] [2] [3]

There is no curative therapy and no clear difference in overall survival (OS) among the treatment options for patients with stage I and stage II mycosis fungoides.

A randomized study of 103 patients compared combined total-skin electron-beam radiation (TSEB) plus combination chemotherapy with conservation therapy consisting of sequential topical therapies. [4] In the latter group, combination chemotherapy was reserved for symptomatic extracutaneous disease or for disease that was refractory to topical therapies. Patients with any disease stage were eligible. Although the complete response rate was higher with combined therapy, toxic effects were considerably greater, and no difference was seen in disease-free or OS between the two groups. [4][Level of evidence: 1iiA]

Treatment Options for Stage I and Stage II Mycosis Fungoides

Treatment options for stages I and II mycosis fungoides include the following: [5]

  1. Photodynamic therapy.
  2. Radiation therapy.
  3. Biologic therapy.
  4. Chemotherapy.
  5. Other drug therapy.
  6. Targeted therapy.

(Refer to the Treatment Option Overview for Mycosis Fungoides (Including SÚzary Syndrome) section of this summary for more information on these treatment options.)

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References:

  1. Kim YH, Jensen RA, Watanabe GL, et al.: Clinical stage IA (limited patch and plaque) mycosis fungoides. A long-term outcome analysis. Arch Dermatol 132 (11): 1309-13, 1996.
  2. Zackheim HS, Amin S, Kashani-Sabet M, et al.: Prognosis in cutaneous T-cell lymphoma by skin stage: long-term survival in 489 patients. J Am Acad Dermatol 40 (3): 418-25, 1999.
  3. Vollmer RT: A review of survival in mycosis fungoides. Am J Clin Pathol 141 (5): 706-11, 2014.
  4. Kaye FJ, Bunn PA Jr, Steinberg SM, 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 321 (26): 1784-90, 1989.
  5. Trautinger F, Knobler R, Willemze R, et al.: EORTC consensus recommendations for the treatment of mycosis fungoides/SÚzary syndrome. Eur J Cancer 42 (8): 1014-30, 2006.
  6. Herrmann JJ, Roenigk HH Jr, Hurria A, et al.: Treatment of mycosis fungoides with photochemotherapy (PUVA): long-term follow-up. J Am Acad Dermatol 33 (2 Pt 1): 234-42, 1995.
  7. Ramsay DL, Lish KM, Yalowitz CB, et al.: Ultraviolet-B phototherapy for early-stage cutaneous T-cell lymphoma. Arch Dermatol 128 (7): 931-3, 1992.
  8. Querfeld C, Rosen ST, Kuzel TM, 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 141 (3): 305-11, 2005.
  9. Kuzel TM, Roenigk HH Jr, Samuelson E, et al.: Effectiveness of interferon alfa-2a combined with phototherapy for mycosis fungoides and the SÚzary syndrome. J Clin Oncol 13 (1): 257-63, 1995.
  10. Olsen EA, Hodak E, Anderson T, et al.: Guidelines for phototherapy of mycosis fungoides and SÚzary syndrome: A consensus statement of the United States Cutaneous Lymphoma Consortium. J Am Acad Dermatol 74 (1): 27-58, 2016.
  11. Chinn DM, Chow S, Kim YH, et al.: Total skin electron beam therapy with or without adjuvant topical nitrogen mustard or nitrogen mustard alone as initial treatment of T2 and T3 mycosis fungoides. Int J Radiat Oncol Biol Phys 43 (5): 951-8, 1999.
  12. Quirˇs PA, Jones GW, Kacinski BM, et al.: Total skin electron beam therapy followed by adjuvant psoralen/ultraviolet-A light in the management of patients with T1 and T2 cutaneous T-cell lymphoma (mycosis fungoides). Int J Radiat Oncol Biol Phys 38 (5): 1027-35, 1997.
  13. Ysebaert L, Truc G, Dalac S, et al.: Ultimate results of radiation therapy for T1-T2 mycosis fungoides (including reirradiation). Int J Radiat Oncol Biol Phys 58 (4): 1128-34, 2004.
  14. Jones GW, Rosenthal D, Wilson LD: Total skin electron radiation for patients with erythrodermic cutaneous T-cell lymphoma (mycosis fungoides and the SÚzary syndrome). Cancer 85 (9): 1985-95, 1999.
  15. Navi D, Riaz N, Levin YS, et al.: The Stanford University experience with conventional-dose, total skin electron-beam therapy in the treatment of generalized patch or plaque (T2) and tumor (T3) mycosis fungoides. Arch Dermatol 147 (5): 561-7, 2011.
  16. Micaily B, Miyamoto C, Kantor G, et al.: Radiotherapy for unilesional mycosis fungoides. Int J Radiat Oncol Biol Phys 42 (2): 361-4, 1998.
  17. Elcin G, Duman N, Karahan S, et al.: Long-term follow-up of early mycosis fungoides patients treated with narrowband ultraviolet B phototherapy. J Dermatolog Treat 25 (3): 268-73, 2014.
  18. Thomas TO, Agrawal P, Guitart J, et al.: Outcome of patients treated with a single-fraction dose of palliative radiation for cutaneous T-cell lymphoma. Int J Radiat Oncol Biol Phys 85 (3): 747-53, 2013.
  19. Olsen EA, Bunn PA: Interferon in the treatment of cutaneous T-cell lymphoma. Hematol Oncol Clin North Am 9 (5): 1089-107, 1995.
  20. Hughes CF, Khot A, McCormack C, et al.: Lack of durable disease control with chemotherapy for mycosis fungoides and SÚzary syndrome: a comparative study of systemic therapy. Blood 125 (1): 71-81, 2015.
  21. Lessin SR, Duvic M, Guitart J, et al.: Topical chemotherapy in cutaneous T-cell lymphoma: positive results of a randomized, controlled, multicenter trial testing the efficacy and safety of a novel mechlorethamine, 0.02%, gel in mycosis fungoides. JAMA Dermatol 149 (1): 25-32, 2013.
  22. de Quatrebarbes J, EstŔve E, Bagot M, et al.: Treatment of early-stage mycosis fungoides with twice-weekly applications of mechlorethamine and topical corticosteroids: a prospective study. Arch Dermatol 141 (9): 1117-20, 2005.
  23. Zackheim HS, Kashani-Sabet M, McMillan A: Low-dose methotrexate to treat mycosis fungoides: a retrospective study in 69 patients. J Am Acad Dermatol 49 (5): 873-8, 2003.
  24. Wollina U, Dummer R, Brockmeyer NH, et al.: Multicenter study of pegylated liposomal doxorubicin in patients with cutaneous T-cell lymphoma. Cancer 98 (5): 993-1001, 2003.
  25. Dummer R, Quaglino P, Becker JC, et al.: Prospective international multicenter phase II trial of intravenous pegylated liposomal doxorubicin monochemotherapy in patients with stage IIB, IVA, or IVB advanced mycosis fungoides: final results from EORTC 21012. J Clin Oncol 30 (33): 4091-7, 2012.
  26. Quereux G, Marques S, Nguyen JM, et al.: Prospective multicenter study of pegylated liposomal doxorubicin treatment in patients with advanced or refractory mycosis fungoides or SÚzary syndrome. Arch Dermatol 144 (6): 727-33, 2008.
  27. Saven A, Carrera CJ, Carson DA, et al.: 2-Chlorodeoxyadenosine: an active agent in the treatment of cutaneous T-cell lymphoma. Blood 80 (3): 587-92, 1992.
  28. Foss FM, Ihde DC, Breneman DL, et al.: Phase II study of pentostatin and intermittent high-dose recombinant interferon alfa-2a in advanced mycosis fungoides/SÚzary syndrome. J Clin Oncol 10 (12): 1907-13, 1992.
  29. Foss FM, Ihde DC, Linnoila IR, et al.: Phase II trial of fludarabine phosphate and interferon alfa-2a in advanced mycosis fungoides/SÚzary syndrome. J Clin Oncol 12 (10): 2051-9, 1994.
  30. Kurzrock R, Pilat S, Duvic M: Pentostatin therapy of T-cell lymphomas with cutaneous manifestations. J Clin Oncol 17 (10): 3117-21, 1999.
  31. Rosen ST, Foss FM: Chemotherapy for mycosis fungoides and the SÚzary syndrome. Hematol Oncol Clin North Am 9 (5): 1109-16, 1995.
  32. Zackheim HS, Epstein EH Jr: Low-dose methotrexate for the SÚzary syndrome. J Am Acad Dermatol 21 (4 Pt 1): 757-62, 1989.
  33. Horwitz SM, Kim YH, Foss F, et al.: Identification of an active, well-tolerated dose of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma. Blood 119 (18): 4115-22, 2012.
  34. Talpur R, Thompson A, Gangar P, et al.: Pralatrexate alone or in combination with bexarotene: long-term tolerability in relapsed/refractory mycosis fungoides. Clin Lymphoma Myeloma Leuk 14 (4): 297-304, 2014.
  35. Duvic M, Hymes K, Heald P, 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 19 (9): 2456-71, 2001.
  36. Heald P, Mehlmauer M, Martin AG, et al.: Topical bexarotene therapy for patients with refractory or persistent early-stage cutaneous T-cell lymphoma: results of the phase III clinical trial. J Am Acad Dermatol 49 (5): 801-15, 2003.
  37. Querfeld C, Rosen ST, Guitart J, et al.: Results of an open-label multicenter phase 2 trial of lenalidomide monotherapy in refractory mycosis fungoides and SÚzary syndrome. Blood 123 (8): 1159-66, 2014.
  38. Duvic M, Dummer R, Becker JC, et al.: Panobinostat activity in both bexarotene-exposed and -na´ve patients with refractory cutaneous T-cell lymphoma: results of a phase II trial. Eur J Cancer 49 (2): 386-94, 2013.
  39. Olsen EA, Kim YH, Kuzel TM, et al.: Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma. J Clin Oncol 25 (21): 3109-15, 2007.
  40. Piekarz RL, Frye R, Turner M, et al.: Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma. J Clin Oncol 27 (32): 5410-7, 2009.
  41. Kim YH, Tavallaee M, Sundram U, et al.: Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides and SÚzary Syndrome With Variable CD30 Expression Level: A Multi-Institution Collaborative Project. J Clin Oncol 33 (32): 3750-8, 2015.
  42. Duvic M, Tetzlaff MT, Gangar P, et al.: Results of a Phase II Trial of Brentuximab Vedotin for CD30+ Cutaneous T-Cell Lymphoma and Lymphomatoid Papulosis. J Clin Oncol 33 (32): 3759-65, 2015.

Stage III and Stage IV Mycosis Fungoides (Including SÚzary Syndrome) Treatment

Mycosis Fungoides

There is no curative therapy and no clear difference in overall survival (OS) among the treatment options for patients with stage III and stage IV disease.

The use of single alkylating agents has produced objective responses in 60% of patients, with a duration of less than 6 months. One of the alkylating agents (e.g., mechlorethamine [nitrogen mustard], cyclophosphamide, or chlorambucil), or the antimetabolite methotrexate is the most frequently used. Single agents have not been shown to cure any patients, and insufficient data exist to determine whether these agents prolong survival. Combination chemotherapy is not definitely superior to single agents. Even in stage IV disease, treatments directed at the skin may provide significant palliation.

A randomized study of 103 patients compared combined total-skin electron-beam radiation (TSEB) plus combination chemotherapy with conservation therapy consisting of sequential topical therapies. [1] In the latter group, combination chemotherapy was reserved for symptomatic extracutaneous disease or for disease refractory to topical therapies. Patients with any stage were eligible. Although the complete response rate was higher with combined therapy, toxic effects were considerably greater, and no difference was seen in disease-free survival or OS between the two groups. [1][Level of evidence: 1iiA]

SÚzary Syndrome

SÚzary Syndrome is a rare leukemic variant of cutaneous T-cell lymphoma characterized by erythroderma, circulating SÚzary cells with cerebriform nuclei, lymphadenopathy, and pruritus. [2] This condition typically progresses rapidly with only short duration of response to most therapies. A retrospective review of 176 patients with SS identified the following poor prognostic factors: [3]

Remissions attained by using extracorporeal photophoresis, alpha interferon, or retinoids may be followed by allogeneic stem cell transplantation. In an anecdotal series of 16 patients with SÚzary syndrome after allogeneic transplant, 9 were in complete remission after 4 years. [4]

Treatment Options for Stage III and Stage IV Mycosis Fungoides (Including SÚzary Syndrome)

Treatment options for stages III and IV mycosis fungoides and SÚzary syndrome include the following (note that in this clinical setting, the skin is easily injured; any of the topical therapies must be administered with extreme caution): [2] [5]

  1. Photodynamic therapy.
  2. Radiation therapy.
  3. Biologic therapy.
  4. Chemotherapy.
  5. Other drug therapy.
  6. Targeted therapy.

(Refer to the Treatment Option Overview for Mycosis Fungoides (Including SÚzary Syndrome) section of this summary for more information on these treatment options.)

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References:

  1. Kaye FJ, Bunn PA Jr, Steinberg SM, 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 321 (26): 1784-90, 1989.
  2. Olsen EA, Rook AH, Zic J, et al.: SÚzary syndrome: immunopathogenesis, literature review of therapeutic options, and recommendations for therapy by the United States Cutaneous Lymphoma Consortium (USCLC). J Am Acad Dermatol 64 (2): 352-404, 2011.
  3. Kubica AW, Davis MD, Weaver AL, et al.: SÚzary syndrome: a study of 176 patients at Mayo Clinic. J Am Acad Dermatol 67 (6): 1189-99, 2012.
  4. Polansky M, Talpur R, Daulat S, et al.: Long-Term Complete Responses to Combination Therapies and Allogeneic Stem Cell Transplants in Patients With SÚzary Syndrome. Clin Lymphoma Myeloma Leuk 15 (5): e83-93, 2015.
  5. Trautinger F, Knobler R, Willemze R, et al.: EORTC consensus recommendations for the treatment of mycosis fungoides/SÚzary syndrome. Eur J Cancer 42 (8): 1014-30, 2006.
  6. Herrmann JJ, Roenigk HH Jr, Hurria A, et al.: Treatment of mycosis fungoides with photochemotherapy (PUVA): long-term follow-up. J Am Acad Dermatol 33 (2 Pt 1): 234-42, 1995.
  7. Ramsay DL, Lish KM, Yalowitz CB, et al.: Ultraviolet-B phototherapy for early-stage cutaneous T-cell lymphoma. Arch Dermatol 128 (7): 931-3, 1992.
  8. Querfeld C, Rosen ST, Kuzel TM, 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 141 (3): 305-11, 2005.
  9. Kuzel TM, Roenigk HH Jr, Samuelson E, et al.: Effectiveness of interferon alfa-2a combined with phototherapy for mycosis fungoides and the SÚzary syndrome. J Clin Oncol 13 (1): 257-63, 1995.
  10. Olsen EA, Hodak E, Anderson T, et al.: Guidelines for phototherapy of mycosis fungoides and SÚzary syndrome: A consensus statement of the United States Cutaneous Lymphoma Consortium. J Am Acad Dermatol 74 (1): 27-58, 2016.
  11. Edelson R, Berger C, Gasparro F, et al.: Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy. Preliminary results. N Engl J Med 316 (6): 297-303, 1987.
  12. Heald PW, Perez MI, McKiernan G, et al.: Extracorporeal photochemotherapy for CTCL. Prog Clin Biol Res 337: 443-7, 1990.
  13. Scarisbrick JJ, Taylor P, Holtick U, et al.: U.K. consensus statement on the use of extracorporeal photopheresis for treatment of cutaneous T-cell lymphoma and chronic graft-versus-host disease. Br J Dermatol 158 (4): 659-78, 2008.
  14. Palareti G, Maccaferri M, Manotti C, et al.: Fibrinogen assays: a collaborative study of six different methods. C.I.S.M.E.L. Comitato Italiano per la Standardizzazione dei Metodi in Ematologia e Laboratorio. Clin Chem 37 (5): 714-9, 1991.
  15. Chinn DM, Chow S, Kim YH, et al.: Total skin electron beam therapy with or without adjuvant topical nitrogen mustard or nitrogen mustard alone as initial treatment of T2 and T3 mycosis fungoides. Int J Radiat Oncol Biol Phys 43 (5): 951-8, 1999.
  16. Quirˇs PA, Jones GW, Kacinski BM, et al.: Total skin electron beam therapy followed by adjuvant psoralen/ultraviolet-A light in the management of patients with T1 and T2 cutaneous T-cell lymphoma (mycosis fungoides). Int J Radiat Oncol Biol Phys 38 (5): 1027-35, 1997.
  17. Ysebaert L, Truc G, Dalac S, et al.: Ultimate results of radiation therapy for T1-T2 mycosis fungoides (including reirradiation). Int J Radiat Oncol Biol Phys 58 (4): 1128-34, 2004.
  18. Jones GW, Rosenthal D, Wilson LD: Total skin electron radiation for patients with erythrodermic cutaneous T-cell lymphoma (mycosis fungoides and the SÚzary syndrome). Cancer 85 (9): 1985-95, 1999.
  19. Navi D, Riaz N, Levin YS, et al.: The Stanford University experience with conventional-dose, total skin electron-beam therapy in the treatment of generalized patch or plaque (T2) and tumor (T3) mycosis fungoides. Arch Dermatol 147 (5): 561-7, 2011.
  20. Micaily B, Miyamoto C, Kantor G, et al.: Radiotherapy for unilesional mycosis fungoides. Int J Radiat Oncol Biol Phys 42 (2): 361-4, 1998.
  21. Elcin G, Duman N, Karahan S, et al.: Long-term follow-up of early mycosis fungoides patients treated with narrowband ultraviolet B phototherapy. J Dermatolog Treat 25 (3): 268-73, 2014.
  22. Thomas TO, Agrawal P, Guitart J, et al.: Outcome of patients treated with a single-fraction dose of palliative radiation for cutaneous T-cell lymphoma. Int J Radiat Oncol Biol Phys 85 (3): 747-53, 2013.
  23. Foss FM, Ihde DC, Breneman DL, et al.: Phase II study of pentostatin and intermittent high-dose recombinant interferon alfa-2a in advanced mycosis fungoides/SÚzary syndrome. J Clin Oncol 10 (12): 1907-13, 1992.
  24. Olsen EA, Bunn PA: Interferon in the treatment of cutaneous T-cell lymphoma. Hematol Oncol Clin North Am 9 (5): 1089-107, 1995.
  25. Zackheim HS, Kashani-Sabet M, McMillan A: Low-dose methotrexate to treat mycosis fungoides: a retrospective study in 69 patients. J Am Acad Dermatol 49 (5): 873-8, 2003.
  26. Saven A, Carrera CJ, Carson DA, et al.: 2-Chlorodeoxyadenosine: an active agent in the treatment of cutaneous T-cell lymphoma. Blood 80 (3): 587-92, 1992.
  27. Foss FM, Ihde DC, Linnoila IR, et al.: Phase II trial of fludarabine phosphate and interferon alfa-2a in advanced mycosis fungoides/SÚzary syndrome. J Clin Oncol 12 (10): 2051-9, 1994.
  28. Kurzrock R, Pilat S, Duvic M: Pentostatin therapy of T-cell lymphomas with cutaneous manifestations. J Clin Oncol 17 (10): 3117-21, 1999.
  29. Hughes CF, Khot A, McCormack C, et al.: Lack of durable disease control with chemotherapy for mycosis fungoides and SÚzary syndrome: a comparative study of systemic therapy. Blood 125 (1): 71-81, 2015.
  30. Rosen ST, Foss FM: Chemotherapy for mycosis fungoides and the SÚzary syndrome. Hematol Oncol Clin North Am 9 (5): 1109-16, 1995.
  31. Zackheim HS, Epstein EH Jr: Low-dose methotrexate for the SÚzary syndrome. J Am Acad Dermatol 21 (4 Pt 1): 757-62, 1989.
  32. Lessin SR, Duvic M, Guitart J, et al.: Topical chemotherapy in cutaneous T-cell lymphoma: positive results of a randomized, controlled, multicenter trial testing the efficacy and safety of a novel mechlorethamine, 0.02%, gel in mycosis fungoides. JAMA Dermatol 149 (1): 25-32, 2013.
  33. de Quatrebarbes J, EstŔve E, Bagot M, et al.: Treatment of early-stage mycosis fungoides with twice-weekly applications of mechlorethamine and topical corticosteroids: a prospective study. Arch Dermatol 141 (9): 1117-20, 2005.
  34. Dummer R, Quaglino P, Becker JC, et al.: Prospective international multicenter phase II trial of intravenous pegylated liposomal doxorubicin monochemotherapy in patients with stage IIB, IVA, or IVB advanced mycosis fungoides: final results from EORTC 21012. J Clin Oncol 30 (33): 4091-7, 2012.
  35. Wollina U, Dummer R, Brockmeyer NH, et al.: Multicenter study of pegylated liposomal doxorubicin in patients with cutaneous T-cell lymphoma. Cancer 98 (5): 993-1001, 2003.
  36. Quereux G, Marques S, Nguyen JM, et al.: Prospective multicenter study of pegylated liposomal doxorubicin treatment in patients with advanced or refractory mycosis fungoides or SÚzary syndrome. Arch Dermatol 144 (6): 727-33, 2008.
  37. Horwitz SM, Kim YH, Foss F, et al.: Identification of an active, well-tolerated dose of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma. Blood 119 (18): 4115-22, 2012.
  38. Talpur R, Thompson A, Gangar P, et al.: Pralatrexate alone or in combination with bexarotene: long-term tolerability in relapsed/refractory mycosis fungoides. Clin Lymphoma Myeloma Leuk 14 (4): 297-304, 2014.
  39. Querfeld C, Rosen ST, Guitart J, et al.: Results of an open-label multicenter phase 2 trial of lenalidomide monotherapy in refractory mycosis fungoides and SÚzary syndrome. Blood 123 (8): 1159-66, 2014.
  40. Duvic M, Hymes K, Heald P, 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 19 (9): 2456-71, 2001.
  41. Heald P, Mehlmauer M, Martin AG, et al.: Topical bexarotene therapy for patients with refractory or persistent early-stage cutaneous T-cell lymphoma: results of the phase III clinical trial. J Am Acad Dermatol 49 (5): 801-15, 2003.
  42. Duvic M, Dummer R, Becker JC, et al.: Panobinostat activity in both bexarotene-exposed and -na´ve patients with refractory cutaneous T-cell lymphoma: results of a phase II trial. Eur J Cancer 49 (2): 386-94, 2013.
  43. Olsen EA, Kim YH, Kuzel TM, et al.: Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma. J Clin Oncol 25 (21): 3109-15, 2007.
  44. Piekarz RL, Frye R, Turner M, et al.: Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma. J Clin Oncol 27 (32): 5410-7, 2009.
  45. Kim YH, Tavallaee M, Sundram U, et al.: Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides and SÚzary Syndrome With Variable CD30 Expression Level: A Multi-Institution Collaborative Project. J Clin Oncol 33 (32): 3750-8, 2015.
  46. Duvic M, Tetzlaff MT, Gangar P, et al.: Results of a Phase II Trial of Brentuximab Vedotin for CD30+ Cutaneous T-Cell Lymphoma and Lymphomatoid Papulosis. J Clin Oncol 33 (32): 3759-65, 2015.

Recurrent Mycosis Fungoides (Including SÚzary Syndrome) Treatment

The treatment of relapsed patients with mycosis fungoides and SÚzary syndrome who have cutaneous T-cell lymphomas involves the joint decisions of the dermatologist, medical oncologist, and radiation oncologist. It may be possible to re-treat localized areas of relapse in the skin with additional electron-beam radiation or possibly to repeat total-skin electron-beam radiation therapy (TSEB). [1] Photon radiation to bulky skin or nodal masses may prove beneficial. If these options are not possible, then continued topical treatment with other modalities such as mechlorethamine or psoralen and ultraviolet A radiation (PUVA) may be warranted to relieve cutaneous symptoms.

Clinical trials, if possible, should be considered as the next therapeutic option.

Treatment Options Under Clinical Evaluation for Recurrent Mycosis Fungoides (Including SÚzary Syndrome)

Treatment options under clinical evaluation for recurrent mycosis fungoides and SÚzary syndrome include the following: [2] [3]

  1. Radiation therapy.
  2. Photodynamic therapy.
  3. Chemotherapy.
  4. Other drug therapy.
  5. Biologic therapy.
  6. Transplantation.
  7. Targeted therapy.

(Refer to the Treatment Option Overview for Mycosis Fungoides (Including SÚzary Syndrome) section of this summary for more information on these treatment options.)

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References:

  1. Becker M, Hoppe RT, Knox SJ: Multiple courses of high-dose total skin electron beam therapy in the management of mycosis fungoides. Int J Radiat Oncol Biol Phys 32 (5): 1445-9, 1995.
  2. Trautinger F, Knobler R, Willemze R, et al.: EORTC consensus recommendations for the treatment of mycosis fungoides/SÚzary syndrome. Eur J Cancer 42 (8): 1014-30, 2006.
  3. Prince HM, Duvic M, Martin A, et al.: Phase III placebo-controlled trial of denileukin diftitox for patients with cutaneous T-cell lymphoma. J Clin Oncol 28 (11): 1870-7, 2010.
  4. Thomas TO, Agrawal P, Guitart J, et al.: Outcome of patients treated with a single-fraction dose of palliative radiation for cutaneous T-cell lymphoma. Int J Radiat Oncol Biol Phys 85 (3): 747-53, 2013.
  5. Elcin G, Duman N, Karahan S, et al.: Long-term follow-up of early mycosis fungoides patients treated with narrowband ultraviolet B phototherapy. J Dermatolog Treat 25 (3): 268-73, 2014.
  6. Kuzel TM, Roenigk HH Jr, Samuelson E, et al.: Effectiveness of interferon alfa-2a combined with phototherapy for mycosis fungoides and the SÚzary syndrome. J Clin Oncol 13 (1): 257-63, 1995.
  7. Edelson R, Berger C, Gasparro F, et al.: Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy. Preliminary results. N Engl J Med 316 (6): 297-303, 1987.
  8. Heald PW, Perez MI, McKiernan G, et al.: Extracorporeal photochemotherapy for CTCL. Prog Clin Biol Res 337: 443-7, 1990.
  9. Horwitz SM, Kim YH, Foss F, et al.: Identification of an active, well-tolerated dose of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma. Blood 119 (18): 4115-22, 2012.
  10. Talpur R, Thompson A, Gangar P, et al.: Pralatrexate alone or in combination with bexarotene: long-term tolerability in relapsed/refractory mycosis fungoides. Clin Lymphoma Myeloma Leuk 14 (4): 297-304, 2014.
  11. Dummer R, Quaglino P, Becker JC, et al.: Prospective international multicenter phase II trial of intravenous pegylated liposomal doxorubicin monochemotherapy in patients with stage IIB, IVA, or IVB advanced mycosis fungoides: final results from EORTC 21012. J Clin Oncol 30 (33): 4091-7, 2012.
  12. Wollina U, Dummer R, Brockmeyer NH, et al.: Multicenter study of pegylated liposomal doxorubicin in patients with cutaneous T-cell lymphoma. Cancer 98 (5): 993-1001, 2003.
  13. Quereux G, Marques S, Nguyen JM, et al.: Prospective multicenter study of pegylated liposomal doxorubicin treatment in patients with advanced or refractory mycosis fungoides or SÚzary syndrome. Arch Dermatol 144 (6): 727-33, 2008.
  14. Kaye FJ, Bunn PA Jr, Steinberg SM, 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 321 (26): 1784-90, 1989.
  15. Rosen ST, Foss FM: Chemotherapy for mycosis fungoides and the SÚzary syndrome. Hematol Oncol Clin North Am 9 (5): 1109-16, 1995.
  16. Zackheim HS, Epstein EH Jr: Low-dose methotrexate for the SÚzary syndrome. J Am Acad Dermatol 21 (4 Pt 1): 757-62, 1989.
  17. Hughes CF, Khot A, McCormack C, et al.: Lack of durable disease control with chemotherapy for mycosis fungoides and SÚzary syndrome: a comparative study of systemic therapy. Blood 125 (1): 71-81, 2015.
  18. Miller VA, Benedetti FM, Rigas JR, et al.: Initial clinical trial of a selective retinoid X receptor ligand, LGD1069. J Clin Oncol 15 (2): 790-5, 1997.
  19. Duvic M, Hymes K, Heald P, 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 19 (9): 2456-71, 2001.
  20. Querfeld C, Rosen ST, Guitart J, et al.: Results of an open-label multicenter phase 2 trial of lenalidomide monotherapy in refractory mycosis fungoides and SÚzary syndrome. Blood 123 (8): 1159-66, 2014.
  21. Duvic M, Dummer R, Becker JC, et al.: Panobinostat activity in both bexarotene-exposed and -na´ve patients with refractory cutaneous T-cell lymphoma: results of a phase II trial. Eur J Cancer 49 (2): 386-94, 2013.
  22. Olsen EA, Kim YH, Kuzel TM, et al.: Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma. J Clin Oncol 25 (21): 3109-15, 2007.
  23. Piekarz RL, Frye R, Turner M, et al.: Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma. J Clin Oncol 27 (32): 5410-7, 2009.
  24. Foss FM, Ihde DC, Breneman DL, et al.: Phase II study of pentostatin and intermittent high-dose recombinant interferon alfa-2a in advanced mycosis fungoides/SÚzary syndrome. J Clin Oncol 10 (12): 1907-13, 1992.
  25. Olsen EA, Bunn PA: Interferon in the treatment of cutaneous T-cell lymphoma. Hematol Oncol Clin North Am 9 (5): 1089-107, 1995.
  26. Molina A, Zain J, Arber DA, et al.: Durable clinical, cytogenetic, and molecular remissions after allogeneic hematopoietic cell transplantation for refractory Sezary syndrome and mycosis fungoides. J Clin Oncol 23 (25): 6163-71, 2005.
  27. Duvic M, Donato M, Dabaja B, et al.: Total skin electron beam and non-myeloablative allogeneic hematopoietic stem-cell transplantation in advanced mycosis fungoides and Sezary syndrome. J Clin Oncol 28 (14): 2365-72, 2010.
  28. Duarte RF, Boumendil A, Onida F, et al.: Long-term outcome of allogeneic hematopoietic cell transplantation for patients with mycosis fungoides and SÚzary syndrome: a European society for blood and marrow transplantation lymphoma working party extended analysis. J Clin Oncol 32 (29): 3347-8, 2014.
  29. Schlaak M, Pickenhain J, Theurich S, et al.: Allogeneic stem cell transplantation versus conventional therapy for advanced primary cutaneous T-cell lymphoma. Cochrane Database Syst Rev 1: CD008908, 2012.
  30. Lechowicz MJ, Lazarus HM, Carreras J, et al.: Allogeneic hematopoietic cell transplantation for mycosis fungoides and Sezary syndrome. Bone Marrow Transplant 49 (11): 1360-5, 2014.
  31. Kim YH, Tavallaee M, Sundram U, et al.: Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides and SÚzary Syndrome With Variable CD30 Expression Level: A Multi-Institution Collaborative Project. J Clin Oncol 33 (32): 3750-8, 2015.
  32. Duvic M, Tetzlaff MT, Gangar P, et al.: Results of a Phase II Trial of Brentuximab Vedotin for CD30+ Cutaneous T-Cell Lymphoma and Lymphomatoid Papulosis. J Clin Oncol 33 (32): 3759-65, 2015.

Key References for Mycosis Fungoides (Including SÚzary Syndrome)

These references have been identified by members of the PDQ Adult Treatment Editorial Board as significant in the field of mycosis fungoides and SÚzary syndrome (MF/SS) treatment. This list is provided to inform users of important studies that have helped shape the current understanding of and treatment options for MF/SS. Listed after each reference are the sections within this summary where the reference is cited.

Changes to This Summary (05/04/2018)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

General Information About Mycosis Fungoides (Including SÚzary Syndrome)

Added Wilcox as reference 1.

Added text to state that another report on 4,459 patients from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program database found that the 19.2% of African Americans with mycosis fungoides have a shorter overall survival, potentially attributable to disease characteristics, socioeconomic status, and type of therapy (cited Su et al. as reference 16).

This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ« - NCI's Comprehensive Cancer Database pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of mycosis fungoides (including SÚzary Syndrome). It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewer for Mycosis Fungoides (Including SÚzary Syndrome) Treatment is:

Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

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The preferred citation for this PDQ summary is:

PDQ« Adult Treatment Editorial Board. PDQ Mycosis Fungoides (Including SÚzary Syndrome) Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/lymphoma/hp/mycosis-fungoides-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389288]

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Date last modified: 2018-05-04

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