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Mycosis Fungoides (Including Sézary Syndrome) Treatment (PDQ®)

  • Last Modified : 2017-07-12

General Information About Mycosis Fungoides (Including Sézary Syndrome) Treatment

Clinical Presentation

Mycosis fungoides (MF) and Sézary syndrome (SS) 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 MF 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. MF/SS is 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 MF. Consultation with a pathologist who has expertise in distinguishing these conditions is important. [5]

Prognosis and Survival

The prognosis of patients with MF/SS is based on the extent of disease at presentation (stage). [6] The presence of lymphadenopathy and involvement of peripheral blood and viscera increase in likelihood with worsening cutaneous involvement and define poor prognostic groups. [6] [7] [8] [9] The Cutaneous Lymphoma International Consortium retrospectively reviewed 1,275 patients and found the following four independent prognostic markers indicate a worse survival: [10]


  • Stage IV disease.

  • Age older than 60 years.

  • Large cell transformation.

  • Elevated lactate dehydrogenase (LDH).

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, MF. [11] [12] In contrast, more than 50% of patients with stage III through stage IV disease die of MF, with a median survival of approximately 5 years. [8] [10] [13] [14] 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 and progression-free survival in both early-stage and advanced-stage groups. [15]

A report on 1,798 patients from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program (SEER) database found an increase in second malignancies (standardized incidence ratio, 1.32; 95% confidence interval, 1.15–1.52), especially for Hodgkin lymphoma, non-Hodgkin lymphoma, and myeloma. [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. [5] [17] Several retrospective studies showed that 20% of patients progress from stage I or II disease to stage III or IV disease. [18] [19] [20] SS presents with generalized erythroderma (T4) and peripheral blood involvement. However, there is some disagreement about whether the MF and SS are actually variants of the same disease. [21] The same retrospective study with a median follow-up of 14.5 years found that only 3% of 1,422 patients progressed from MF to SS. [18]

There is consensus that patients with SS have a poor prognosis (median survival, 4 years). [22] 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. [23] [24] [25] 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. [26] 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. [17]


Reference
  1. Girardi M, Heald PW, Wilson LD: The pathogenesis of mycosis fungoides. N Engl J Med 350 (19): 1978-88, 2004.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  4. Diamandidou E, Cohen PR, Kurzrock R: Mycosis fungoides and Sezary syndrome. Blood 88 (7): 2385-409, 1996.[PUBMED Abstract]

  5. 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.[PUBMED Abstract]

  6. Agar NS, Wedgeworth E, Crichton S, et al.: Survival outcomes and prognostic factors in mycosis fungoides/Sézary 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.[PUBMED Abstract]

  7. Talpur R, Singh L, Daulat S, et al.: Long-term outcomes of 1,263 patients with mycosis fungoides and Sézary syndrome from 1982 to 2009. Clin Cancer Res 18 (18): 5051-60, 2012.[PUBMED Abstract]

  8. 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.[PUBMED Abstract]

  9. Alberti-Violetti S, Talpur R, Schlichte M, et al.: Advanced-stage mycosis fungoides and Sézary syndrome: survival and response to treatment. Clin Lymphoma Myeloma Leuk 15 (6): e105-12, 2015.[PUBMED Abstract]

  10. Scarisbrick JJ, Prince HM, Vermeer MH, et al.: Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and Sézary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model. J Clin Oncol 33 (32): 3766-73, 2015.[PUBMED Abstract]

  11. 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.[PUBMED Abstract]

  12. Vollmer RT: A review of survival in mycosis fungoides. Am J Clin Pathol 141 (5): 706-11, 2014.[PUBMED Abstract]

  13. 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.[PUBMED Abstract]

  14. 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.[PUBMED Abstract]

  15. 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.[PUBMED Abstract]

  16. 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.[PUBMED Abstract]

  17. Lorincz AL: Cutaneous T-cell lymphoma (mycosis fungoides) Lancet 347 (9005): 871-6, 1996.[PUBMED Abstract]

  18. 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.[PUBMED Abstract]

  19. 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.[PUBMED Abstract]

  20. Desai M, Liu S, Parker S: Clinical characteristics, prognostic factors, and survival of 393 patients with mycosis fungoides and Sézary syndrome in the southeastern United States: a single-institution cohort. J Am Acad Dermatol 72 (2): 276-85, 2015.[PUBMED Abstract]

  21. Olsen EA, Rook AH, Zic J, et al.: Sézary 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.[PUBMED Abstract]

  22. Kubica AW, Davis MD, Weaver AL, et al.: Sézary syndrome: a study of 176 patients at Mayo Clinic. J Am Acad Dermatol 67 (6): 1189-99, 2012.[PUBMED Abstract]

  23. Kim YH, Bishop K, Varghese A, et al.: Prognostic factors in erythrodermic mycosis fungoides and the Sézary syndrome. Arch Dermatol 131 (9): 1003-8, 1995.[PUBMED Abstract]

  24. 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.[PUBMED Abstract]

  25. 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.[PUBMED Abstract]

  26. 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.[PUBMED Abstract]

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Cellular Classification of Mycosis Fungoides (Including Sézary Syndrome)

The histologic diagnosis of mycosis fungoides and Sézary syndrome (MF/SS) 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 MF/SS cells (convoluted lymphocytes), a band-like upper dermal infiltrate, and epidermal infiltrations with Pautrier abscesses (collections of neoplastic lymphocytes). A definitive diagnosis of SS may be made from a peripheral blood evaluation when skin biopsies are consistent with the diagnosis. Supportive evidence for circulating Sézary 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]


Reference
  1. Olsen EA, Rook AH, Zic J, et al.: Sézary 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.[PUBMED Abstract]

  2. Fraser-Andrews EA, Russell-Jones R, Woolford AJ, et al.: Diagnostic and prognostic importance of T-cell receptor gene analysis in patients with Sézary syndrome. Cancer 92 (7): 1745-52, 2001.[PUBMED Abstract]

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Stage Information for Mycosis Fungoides (Including Sézary Syndrome)

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

MF/SS 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 American Joint Committee on Cancer (AJCC) has designated staging by TNM classification to define MF. [3]

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

EORTC = European Organization of Research and Treatment of Cancer; ISCL = International Society for Cutaneous Lymphomas; 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, Sézary cells are defined as lymphocytes with hyperconvoluted cerebriform nuclei. If Sézary 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.
T1 Limited patchesb papules, and/or plaquesc covering <10% of the skin surface. May further stratify into T1a (patch only) vs. T1b (plaque ± patch).
T2 Patches, 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).
T4 Confluence of erythema covering ≥80% of body surface area.

Node

N0 No clinically abnormal peripheral lymph nodes;e biopsy not required.
N1 Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 1 or NCI LN0–2.
N1a Clone negativef.
N1b Clone positivef.
N2 Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 2 or NCI LN3.
N2a Clone negativef.
N2b Clone positivef.
N3 Clinically abnormal peripheral lymph nodes; histopathology Dutch grades 3–4 or NCI LN4; clone positive or negative.
Nx Clinically abnormal peripheral lymph nodes; no histologic confirmation.

Visceral

M0 No visceral organ involvement.
M1 Visceral involvement (must have pathology confirmationg, and organ involved should be specified).

Peripheral Blood Involvement

B0 Absence of significant blood involvement: ≤5% of peripheral blood lymphocytes are atypical (Sézary) cellsh.
B0a Clone negativef.
B0b Clone positivef.
B1 Low blood-tumor burden: >5% of peripheral blood lymphocytes are atypical (Sézary) cells but does not meet the criteria of B2.
B1a Clone negativef.
B1b Clone positivef.
B2 High blood-tumor burden: ≥1,000/μL Sézary cellsh with positive clonef.


Table 2. Anatomic Stage/Prognostic Groupsa, b

ISCL/EORTC Revision to the Staging of Mycosis Fungoides (Including Sézary Syndrome)
Stage T N M Peripheral Blood Involvement
EORTC = European Organization of Research and Treatment of Cancer; ISCL = International Society for Cutaneous Lymphomas.
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]
IA 1 0 0 0, 1
IB 2 0 0 0, 1
IIA 1, 2 1, 2 0 0, 1
IIB 3 0–2 0 0, 1
III 4 0–2 0 0, 1
IIIA 4 0–2 0 0
IIIB 4 0–2 0 1
IVA1 1–4 0–2 0 2
IVA2 1–4 3 0 0–2
IVB 1–4 0–3 1 0–2


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


Reference
  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.[PUBMED Abstract]

  2. Agar NS, Wedgeworth E, Crichton S, et al.: Survival outcomes and prognostic factors in mycosis fungoides/Sézary 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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  4. Olsen EA, Whittaker S, Kim YH, et al.: Clinical end points and response criteria in mycosis fungoides and Sézary 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.[PUBMED Abstract]

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Treatment Option Overview for Mycosis Fungoides (Including Sézary Syndrome)

Treatment options

for patients mycosis fungoides and Sézary syndrome (MF/SS) include the following: [1] [2] [3]

Photodynamic Therapy

  1. Psoralen and ultraviolet A radiation (PUVA).
    • Therapeutic trials with PUVA have shown a 62% to 90% complete remission rate with early cutaneous stages achieving the best responses. PUVA may be used in conjunction with systemic treatment. [4] Continued maintenance therapy with PUVA at more protracted intervals is generally required to prolong remission duration. [4] [5] [6] [7] PUVA combined with interferon alpha-2a is associated with a high response rate. [4] [8]

  2. Extracorporeal photochemotherapy alone [9] [10] [11] or in combination with total-skin electron-beam radiation (TSEB). [12]

Radiation Therapy

  1. TSEB.
    • Electron radiation of appropriate energies will penetrate only to the dermis, and thus the skin alone can be treated without systemic effects. This therapy requires a radiation therapy facility with physics support and considerable technical expertise to deliver precise dosimetry. TSEB can result in short- and long-term cutaneous toxic effects and is not widely available.

    • This therapy can provide excellent palliation, with complete response rates of as much as 80%, and may be combined with systemic treatment. Based on the long-term survival of these early-stage patients, electron-beam radiation therapy is sometimes used with curative intent. [13] [14] [15] [16] [17] Long-term disease-free survival (DFS) can be achieved in patients with unilesional MF treated with local radiation therapy. [18]

  2. Ultraviolet B radiation (UVB) or ultraviolet A radiation (UVA). [4] [19]
  3. Local electron-beam radiation or orthovoltage radiation therapy may be used to palliate areas of bulky or symptomatic skin disease. [20]

Biologic Therapy

  1. Interferon alpha or interferon gamma alone or in combination with topical therapy. [21] [22]
    • A retrospective review of 198 patients with MF /SS compared time to next treatment (TTNT) between interferon alpha and conventional chemotherapy. Interferon alpha provided a longer TTNT of 8.7 months (95% confidence interval [CI], 6.0–18.0) than did chemotherapy, with a TTNT of 3.9 months (95% CI, 3.2–5.1) and P < .00001. [23] [Level of evidence: 3iiiDiv]

Chemotherapy

  1. Topical chemotherapy with mechlorethamine (nitrogen mustard).
    • This form of treatment may be used palliatively or to supplement therapeutic approaches directed against nodal or visceral disease. Topical application of mechlorethamine has produced regression of cutaneous lesions, with particular efficacy in early stages of disease. The overall complete remission rate is related to skin stage; 50% to 80% of TNM classification T1 patients, 25% to 75% of T2 patients, as many as 50% of T3 patients, and 20% to 40% of T4 patients have complete responses. The overall complete remission rate in 243 patients was 64% and was related to stage; as many as 35% of stage IV patients had complete responses. Treatments are usually continued for 2 to 3 years. Continuous 5-year DFS may be possible in as many as 33% of T1 patients. [13] [24] [25]

  2. Oral methotrexate (NCT00425555). [26]
  3. Pegylated liposomal doxorubicin. [27] [28] [29]
  4. Fludarabine, 2-chlorodeoxyadenosine, and pentostatin are active agents for MF/SS. [22] [30] [31] [32]
    • Chemotherapeutic agents generally demonstrate short durations of response. In a retrospective review of 198 patients with advanced-stage disease, the median time before patients required new therapy was 4 months. [23] However, these comparisons may be confounded by the order in which the agents were introduced.

  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. [23] [33] [34] [35]
    • Chemotherapeutic agents generally demonstrate short durations of response. In a retrospective review of 198 patients with advanced-stage disease, the median time before patients required new therapy was 4 months. [23] However, these comparisons may be confounded by the order in which the agents were introduced.

  6. Pralatrexate (folate analog). [36] [37]
    • Chemotherapeutic agents generally demonstrate short durations of response. In a retrospective review of 198 patients with advanced-stage disease, the median time before patients required new therapy was 4 months. [23]

Other Drug Therapy

  1. Symptomatic management with topical corticosteroids.
  2. Bexarotene, an oral or topical retinoid (NCT00255801). [38] [39]
  3. Lenalidomide. [40]
  4. Vorinostat or romidepsin or other histone deacetylase inhibitors (HDACi). [3] [41] [42] [43]
    • A retrospective review of 198 patients with MF SS compared TTNT between HDACi and conventional chemotherapy. HDACi provided a longer TTNT of 4.5 months (95% CI, 4.0–6.1) than did chemotherapy, with a TTNT of 3.9 months (95% CI, 3.2–5.1 P = .01). [23] [Level of evidence: 3iiiDiv]

Targeted Therapy

  1. Brentuximab vedotin. [44] [45]
    • Two phase II trials of 58 patients with variable CD30 expression showed a 50% to 70% response rate with 50% of patients still in remission after 1 year. [44] [45] [Level of evidence: 3iiiDiv]

Transplantation

  1. Allogeneic or autologous bone marrow transplantation. [46] [47] [48] [48] [49]
    • Among these highly selected patients, the 5-year overall survival rate ranges from 30% to 50%, with a relapse-free survival rate of 15% to 25%. [46] [47] [48] [48] [49] [50]

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 MF/SS are candidates for clinical trials evaluating new approaches to treatment.


Reference
  1. Prince HM, Whittaker S, Hoppe RT: How I treat mycosis fungoides and Sézary syndrome. Blood 114 (20): 4337-53, 2009.[PUBMED Abstract]

  2. Trautinger F, Knobler R, Willemze R, et al.: EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome. Eur J Cancer 42 (8): 1014-30, 2006.[PUBMED Abstract]

  3. Olsen EA, Rook AH, Zic J, et al.: Sézary 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.[PUBMED Abstract]

  4. Olsen EA, Hodak E, Anderson T, et al.: Guidelines for phototherapy of mycosis fungoides and Sézary syndrome: A consensus statement of the United States Cutaneous Lymphoma Consortium. J Am Acad Dermatol 74 (1): 27-58, 2016.[PUBMED Abstract]

  5. 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.[PUBMED Abstract]

  6. 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.[PUBMED Abstract]

  7. 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.[PUBMED Abstract]

  8. Kuzel TM, Roenigk HH Jr, Samuelson E, et al.: Effectiveness of interferon alfa-2a combined with phototherapy for mycosis fungoides and the Sézary syndrome. J Clin Oncol 13 (1): 257-63, 1995.[PUBMED Abstract]

  9. 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.[PUBMED Abstract]

  10. Heald PW, Perez MI, McKiernan G, et al.: Extracorporeal photochemotherapy for CTCL. Prog Clin Biol Res 337: 443-7, 1990.[PUBMED Abstract]

  11. 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.[PUBMED Abstract]

  12. 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.[PUBMED Abstract]

  13. 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.[PUBMED Abstract]

  14. Quirós 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.[PUBMED Abstract]

  15. 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.[PUBMED Abstract]

  16. Jones GW, Rosenthal D, Wilson LD: Total skin electron radiation for patients with erythrodermic cutaneous T-cell lymphoma (mycosis fungoides and the Sézary syndrome). Cancer 85 (9): 1985-95, 1999.[PUBMED Abstract]

  17. 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.[PUBMED Abstract]

  18. Micaily B, Miyamoto C, Kantor G, et al.: Radiotherapy for unilesional mycosis fungoides. Int J Radiat Oncol Biol Phys 42 (2): 361-4, 1998.[PUBMED Abstract]

  19. 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.[PUBMED Abstract]

  20. 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.[PUBMED Abstract]

  21. Olsen EA, Bunn PA: Interferon in the treatment of cutaneous T-cell lymphoma. Hematol Oncol Clin North Am 9 (5): 1089-107, 1995.[PUBMED Abstract]

  22. 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/Sézary syndrome. J Clin Oncol 10 (12): 1907-13, 1992.[PUBMED Abstract]

  23. Hughes CF, Khot A, McCormack C, et al.: Lack of durable disease control with chemotherapy for mycosis fungoides and Sézary syndrome: a comparative study of systemic therapy. Blood 125 (1): 71-81, 2015.[PUBMED Abstract]

  24. 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.[PUBMED Abstract]

  25. de Quatrebarbes J, Estève 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.[PUBMED Abstract]

  26. 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.[PUBMED Abstract]

  27. 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.[PUBMED Abstract]

  28. 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.[PUBMED Abstract]

  29. 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 Sézary syndrome. Arch Dermatol 144 (6): 727-33, 2008.[PUBMED Abstract]

  30. 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.[PUBMED Abstract]

  31. Foss FM, Ihde DC, Linnoila IR, et al.: Phase II trial of fludarabine phosphate and interferon alfa-2a in advanced mycosis fungoides/Sézary syndrome. J Clin Oncol 12 (10): 2051-9, 1994.[PUBMED Abstract]

  32. Kurzrock R, Pilat S, Duvic M: Pentostatin therapy of T-cell lymphomas with cutaneous manifestations. J Clin Oncol 17 (10): 3117-21, 1999.[PUBMED Abstract]

  33. 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.[PUBMED Abstract]

  34. Rosen ST, Foss FM: Chemotherapy for mycosis fungoides and the Sézary syndrome. Hematol Oncol Clin North Am 9 (5): 1109-16, 1995.[PUBMED Abstract]

  35. Zackheim HS, Epstein EH Jr: Low-dose methotrexate for the Sézary syndrome. J Am Acad Dermatol 21 (4 Pt 1): 757-62, 1989.[PUBMED Abstract]

  36. 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.[PUBMED Abstract]

  37. 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.[PUBMED Abstract]

  38. 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.[PUBMED Abstract]

  39. 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.[PUBMED Abstract]

  40. 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 Sézary syndrome. Blood 123 (8): 1159-66, 2014.[PUBMED Abstract]

  41. Duvic M, Dummer R, Becker JC, et al.: Panobinostat activity in both bexarotene-exposed and -naïve patients with refractory cutaneous T-cell lymphoma: results of a phase II trial. Eur J Cancer 49 (2): 386-94, 2013.[PUBMED Abstract]

  42. 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.[PUBMED Abstract]

  43. 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.[PUBMED Abstract]

  44. Kim YH, Tavallaee M, Sundram U, et al.: Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides and Sézary Syndrome With Variable CD30 Expression Level: A Multi-Institution Collaborative Project. J Clin Oncol 33 (32): 3750-8, 2015.[PUBMED Abstract]

  45. 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.[PUBMED Abstract]

  46. 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.[PUBMED Abstract]

  47. 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.[PUBMED Abstract]

  48. Duarte RF, Boumendil A, Onida F, et al.: Long-term outcome of allogeneic hematopoietic cell transplantation for patients with mycosis fungoides and Sézary syndrome: a European society for blood and marrow transplantation lymphoma working party extended analysis. J Clin Oncol 32 (29): 3347-8, 2014.[PUBMED Abstract]

  49. 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.[PUBMED Abstract]

  50. 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.[PUBMED Abstract]

 | 

Stage I and Stage II Mycosis Fungoides

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 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 (MF).

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 MF include the following: [5]

  1. Photodynamic therapy.
    • Psoralen and ultraviolet A (PUVA) radiation. [6] [7] [8] [9] [10]

  2. Radiation therapy.
    • TSEB. [11] [12] [13] [14] [15] [16]

    • Ultraviolet B (UVB) radiation . [17]

    • Local electron-beam radiation or orthovoltage radiation therapy may be used to palliate areas of bulky or symptomatic skin disease. [18]

  3. Biologic therapy.
    • Interferon alpha or interferon gamma alone or in combination with topical therapy. [19] [20] [Level of evidence: 3iiiDiv]

  4. Chemotherapy.
    • Topical chemotherapy with mechlorethamine (nitrogen mustard). [11] [21] [22]

    • Oral methotrexate (NCT00425555). [23]

    • Pegylated liposomal doxorubicin. [24] [25] [26]

    • Fludarabine, 2-chlorodeoxyadenosine, and pentostatin are active agents for MF. [27] [28] [29] [30]

    • Single-agent chemotherapy or combination systemic chemotherapy (chlorambucil plus prednisone, mechlorethamine, cyclophosphamide, methotrexate, and combination chemotherapy) often combined with treatment directed at the skin. [4] [20] [31] [32]

    • Pralatrexate (folate analog). [20] [33] [34]

  5. Other drug therapy.
    • Symptomatic management with topical corticosteroids.

    • Bexarotene, an oral or topical retinoid (NCT00255801). [35] [36]

    • Lenalidomide. [37]

    • Vorinostat or romidepsin or other histone deacetylase inhibitors. [20] [38] [39] [40] [Level of evidence: 3iiiDiv]

  6. Targeted therapy.
    • Brentuximab vedotin. [41] [42]

(Refer to the Treatment Option Overview for Mycosis Fungoides (Including Sézary Syndrome) for more information on these treatment options.)

Current Clinical Trials

Check the list of NCI-supported cancer clinical trials that are now accepting patients with stage I mycosis fungoides/Sezary syndrome and stage II mycosis fungoides/Sezary syndrome. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI website.


Reference
  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  3. Vollmer RT: A review of survival in mycosis fungoides. Am J Clin Pathol 141 (5): 706-11, 2014.[PUBMED Abstract]

  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.[PUBMED Abstract]

  5. Trautinger F, Knobler R, Willemze R, et al.: EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome. Eur J Cancer 42 (8): 1014-30, 2006.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  9. Kuzel TM, Roenigk HH Jr, Samuelson E, et al.: Effectiveness of interferon alfa-2a combined with phototherapy for mycosis fungoides and the Sézary syndrome. J Clin Oncol 13 (1): 257-63, 1995.[PUBMED Abstract]

  10. Olsen EA, Hodak E, Anderson T, et al.: Guidelines for phototherapy of mycosis fungoides and Sézary syndrome: A consensus statement of the United States Cutaneous Lymphoma Consortium. J Am Acad Dermatol 74 (1): 27-58, 2016.[PUBMED Abstract]

  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.[PUBMED Abstract]

  12. Quirós 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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  14. Jones GW, Rosenthal D, Wilson LD: Total skin electron radiation for patients with erythrodermic cutaneous T-cell lymphoma (mycosis fungoides and the Sézary syndrome). Cancer 85 (9): 1985-95, 1999.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  19. Olsen EA, Bunn PA: Interferon in the treatment of cutaneous T-cell lymphoma. Hematol Oncol Clin North Am 9 (5): 1089-107, 1995.[PUBMED Abstract]

  20. Hughes CF, Khot A, McCormack C, et al.: Lack of durable disease control with chemotherapy for mycosis fungoides and Sézary syndrome: a comparative study of systemic therapy. Blood 125 (1): 71-81, 2015.[PUBMED Abstract]

  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.[PUBMED Abstract]

  22. de Quatrebarbes J, Estève 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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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 Sézary syndrome. Arch Dermatol 144 (6): 727-33, 2008.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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/Sézary syndrome. J Clin Oncol 10 (12): 1907-13, 1992.[PUBMED Abstract]

  29. Foss FM, Ihde DC, Linnoila IR, et al.: Phase II trial of fludarabine phosphate and interferon alfa-2a in advanced mycosis fungoides/Sézary syndrome. J Clin Oncol 12 (10): 2051-9, 1994.[PUBMED Abstract]

  30. Kurzrock R, Pilat S, Duvic M: Pentostatin therapy of T-cell lymphomas with cutaneous manifestations. J Clin Oncol 17 (10): 3117-21, 1999.[PUBMED Abstract]

  31. Rosen ST, Foss FM: Chemotherapy for mycosis fungoides and the Sézary syndrome. Hematol Oncol Clin North Am 9 (5): 1109-16, 1995.[PUBMED Abstract]

  32. Zackheim HS, Epstein EH Jr: Low-dose methotrexate for the Sézary syndrome. J Am Acad Dermatol 21 (4 Pt 1): 757-62, 1989.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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 Sézary syndrome. Blood 123 (8): 1159-66, 2014.[PUBMED Abstract]

  38. Duvic M, Dummer R, Becker JC, et al.: Panobinostat activity in both bexarotene-exposed and -naïve patients with refractory cutaneous T-cell lymphoma: results of a phase II trial. Eur J Cancer 49 (2): 386-94, 2013.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  41. Kim YH, Tavallaee M, Sundram U, et al.: Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides and Sézary Syndrome With Variable CD30 Expression Level: A Multi-Institution Collaborative Project. J Clin Oncol 33 (32): 3750-8, 2015.[PUBMED Abstract]

  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.[PUBMED Abstract]

 | 

Stage III and Stage IV Mycosis Fungoides (Including Sézary Syndrome)

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, 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 or OS between the two groups. [1] [Level of evidence: 1iiA]

Sézary Syndrome

Sézary Syndrome (SS) is a rare leukemic variant of cutaneous T-cell lymphoma characterized by erythroderma, circulating Sézary 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]


  • High lactate dehydrogenase.

  • Previous diagnosis of mycosis fungoides (MF).

  • Presence of T-cell receptor gene rearrangements in skin, blood, or both.

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 SS after allogeneic transplant, 9 were in complete remission after 4 years. [4]

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

Treatment options for stages III and IV mycosis fungoides (MF) (including SS) 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.
    • Psoralen and ultraviolet A (PUVA) radiation. [6] [7] [8] [9] [10]

    • Extracorporeal photochemotherapy alone [11] [12] [13] or in combination with TSEB. [14]

  2. Radiation therapy.
    • TSEB. [15] [16] [17] [18] [19] [20]

    • Ultraviolet B (UVB) radiation and ultraviolet A (UVA) radiation. [10] [21]

    • Local electron-beam radiation or orthovoltage radiation therapy may be used to palliate areas of bulky or symptomatic disease. [22]

  3. Biologic therapy.
    • Interferon alpha alone or in combination with other agents, such as topical therapy. [23] [24]

  4. Chemotherapy.
    • Oral methotrexate (NCT00425555). [25]

    • Fludarabine, 2-chlorodeoxyadenosine, and pentostatin are active agents for MF/SS. [23] [26] [27] [28] [29]

    • Single-agent chemotherapy or combination systemic chemotherapy (chlorambucil plus prednisone, mechlorethamine, cyclophosphamide, methotrexate, and combination chemotherapy) often combined with treatment directed at the skin. [1] [29] [30] [31]

    • Topical chemotherapy with mechlorethamine (nitrogen mustard). [32] [33]

    • Pegylated liposomal doxorubicin. [34] [35] [36]

    • Pralatrexate (folate analog). [29] [37] [38]

  5. Other drug therapy.
    • Symptomatic management with topical corticosteroids.

    • Lenalidomide. [39]

    • Bexarotene, an oral or topical retinoid. [40] [41]

    • Vorinostat or romidepsin or other histone deacetylase inhibitors. [2] [42] [43] [44]

  6. Targeted therapy.
    • Brentuximab vedotin. [45] [46]

(Refer to the Treatment Option Overview for Mycosis Fungoides (Including Sézary Syndrome) for more information on these treatment options.)

Current Clinical Trials

Check the list of NCI-supported cancer clinical trials that are now accepting patients with stage III mycosis fungoides/Sezary syndrome and stage IV mycosis fungoides/Sezary syndrome. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI website.


Reference
  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.[PUBMED Abstract]

  2. Olsen EA, Rook AH, Zic J, et al.: Sézary 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.[PUBMED Abstract]

  3. Kubica AW, Davis MD, Weaver AL, et al.: Sézary syndrome: a study of 176 patients at Mayo Clinic. J Am Acad Dermatol 67 (6): 1189-99, 2012.[PUBMED Abstract]

  4. Polansky M, Talpur R, Daulat S, et al.: Long-Term Complete Responses to Combination Therapies and Allogeneic Stem Cell Transplants in Patients With Sézary Syndrome. Clin Lymphoma Myeloma Leuk 15 (5): e83-93, 2015.[PUBMED Abstract]

  5. Trautinger F, Knobler R, Willemze R, et al.: EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome. Eur J Cancer 42 (8): 1014-30, 2006.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  9. Kuzel TM, Roenigk HH Jr, Samuelson E, et al.: Effectiveness of interferon alfa-2a combined with phototherapy for mycosis fungoides and the Sézary syndrome. J Clin Oncol 13 (1): 257-63, 1995.[PUBMED Abstract]

  10. Olsen EA, Hodak E, Anderson T, et al.: Guidelines for phototherapy of mycosis fungoides and Sézary syndrome: A consensus statement of the United States Cutaneous Lymphoma Consortium. J Am Acad Dermatol 74 (1): 27-58, 2016.[PUBMED Abstract]

  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.[PUBMED Abstract]

  12. Heald PW, Perez MI, McKiernan G, et al.: Extracorporeal photochemotherapy for CTCL. Prog Clin Biol Res 337: 443-7, 1990.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  16. Quirós 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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  18. Jones GW, Rosenthal D, Wilson LD: Total skin electron radiation for patients with erythrodermic cutaneous T-cell lymphoma (mycosis fungoides and the Sézary syndrome). Cancer 85 (9): 1985-95, 1999.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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/Sézary syndrome. J Clin Oncol 10 (12): 1907-13, 1992.[PUBMED Abstract]

  24. Olsen EA, Bunn PA: Interferon in the treatment of cutaneous T-cell lymphoma. Hematol Oncol Clin North Am 9 (5): 1089-107, 1995.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  27. Foss FM, Ihde DC, Linnoila IR, et al.: Phase II trial of fludarabine phosphate and interferon alfa-2a in advanced mycosis fungoides/Sézary syndrome. J Clin Oncol 12 (10): 2051-9, 1994.[PUBMED Abstract]

  28. Kurzrock R, Pilat S, Duvic M: Pentostatin therapy of T-cell lymphomas with cutaneous manifestations. J Clin Oncol 17 (10): 3117-21, 1999.[PUBMED Abstract]

  29. Hughes CF, Khot A, McCormack C, et al.: Lack of durable disease control with chemotherapy for mycosis fungoides and Sézary syndrome: a comparative study of systemic therapy. Blood 125 (1): 71-81, 2015.[PUBMED Abstract]

  30. Rosen ST, Foss FM: Chemotherapy for mycosis fungoides and the Sézary syndrome. Hematol Oncol Clin North Am 9 (5): 1109-16, 1995.[PUBMED Abstract]

  31. Zackheim HS, Epstein EH Jr: Low-dose methotrexate for the Sézary syndrome. J Am Acad Dermatol 21 (4 Pt 1): 757-62, 1989.[PUBMED Abstract]

  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.[PUBMED Abstract]

  33. de Quatrebarbes J, Estève 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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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 Sézary syndrome. Arch Dermatol 144 (6): 727-33, 2008.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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 Sézary syndrome. Blood 123 (8): 1159-66, 2014.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  42. Duvic M, Dummer R, Becker JC, et al.: Panobinostat activity in both bexarotene-exposed and -naïve patients with refractory cutaneous T-cell lymphoma: results of a phase II trial. Eur J Cancer 49 (2): 386-94, 2013.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  45. Kim YH, Tavallaee M, Sundram U, et al.: Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides and Sézary Syndrome With Variable CD30 Expression Level: A Multi-Institution Collaborative Project. J Clin Oncol 33 (32): 3750-8, 2015.[PUBMED Abstract]

  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.[PUBMED Abstract]

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Recurrent Mycosis Fungoides (Including Sézary Syndrome)

The treatment of relapsed patients with mycosis fungoides (MF) (including Sézary syndrome [SS]) with 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 Sézary Syndrome)

Treatment options under clinical evaluation for recurrent mycosis fungoides and Sézary Syndrome (MF/SS) include the following: [2] [3]

  1. Radiation therapy.
    • Additional electron-beam radiation or a repeat of TSEB.

    • Photon radiation to bulky skin or nodal masses. [4]

    • Ultraviolet B (UVB) radiation. [5]

  2. Photodynamic therapy.
    • Topical treatment with mechlorethamine or PUVA.

    • PUVA combined with interferon alpha-2a is associated with a high response rate. [6]

    • Extracorporeal photochemotherapy has produced tumor regression in patients resistant to other therapies. [7] [8]

  3. Chemotherapy.
    • Pralatrexate (folate analog). [9] [10]

    • Pegylated liposomal doxorubicin. [11] [12] [13]

    • Systemic chemotherapy: chlorambucil plus prednisone, mechlorethamine, cyclophosphamide, methotrexate, and combination chemotherapy. [14] [15] [16] [17]

  4. Other drug therapy.
    • Symptomatic management with topical corticosteroids.

    • Bexarotene is a retinoid available in an oral or topical form. [18] [19]

    • Lenalidomide. [20]

    • Vorinostat or romidepsin or other histone deacetylase inhibitors. [21] [22] [23]

  5. Biologic therapy.
    • Interferon alpha alone or in combination with other agents, such as topical therapy. [24] [25]

  6. Transplantation.
    • Allogeneic bone marrow or stem cell transplantation. [26] [27] [28] [28] [29] [30]

  7. Targeted therapy.
    • Brentuximab vedotin. [31] [32]

(Refer to the Treatment Option Overview for Mycosis Fungoides (Including Sézary Syndrome) for more information on these treatment options.)

Current Clinical Trials

Check the list of NCI-supported cancer clinical trials that are now accepting patients with recurrent mycosis fungoides/Sezary syndrome. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI website.


Reference
  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.[PUBMED Abstract]

  2. Trautinger F, Knobler R, Willemze R, et al.: EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome. Eur J Cancer 42 (8): 1014-30, 2006.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  6. Kuzel TM, Roenigk HH Jr, Samuelson E, et al.: Effectiveness of interferon alfa-2a combined with phototherapy for mycosis fungoides and the Sézary syndrome. J Clin Oncol 13 (1): 257-63, 1995.[PUBMED Abstract]

  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.[PUBMED Abstract]

  8. Heald PW, Perez MI, McKiernan G, et al.: Extracorporeal photochemotherapy for CTCL. Prog Clin Biol Res 337: 443-7, 1990.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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 Sézary syndrome. Arch Dermatol 144 (6): 727-33, 2008.[PUBMED Abstract]

  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.[PUBMED Abstract]

  15. Rosen ST, Foss FM: Chemotherapy for mycosis fungoides and the Sézary syndrome. Hematol Oncol Clin North Am 9 (5): 1109-16, 1995.[PUBMED Abstract]

  16. Zackheim HS, Epstein EH Jr: Low-dose methotrexate for the Sézary syndrome. J Am Acad Dermatol 21 (4 Pt 1): 757-62, 1989.[PUBMED Abstract]

  17. Hughes CF, Khot A, McCormack C, et al.: Lack of durable disease control with chemotherapy for mycosis fungoides and Sézary syndrome: a comparative study of systemic therapy. Blood 125 (1): 71-81, 2015.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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 Sézary syndrome. Blood 123 (8): 1159-66, 2014.[PUBMED Abstract]

  21. Duvic M, Dummer R, Becker JC, et al.: Panobinostat activity in both bexarotene-exposed and -naïve patients with refractory cutaneous T-cell lymphoma: results of a phase II trial. Eur J Cancer 49 (2): 386-94, 2013.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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/Sézary syndrome. J Clin Oncol 10 (12): 1907-13, 1992.[PUBMED Abstract]

  25. Olsen EA, Bunn PA: Interferon in the treatment of cutaneous T-cell lymphoma. Hematol Oncol Clin North Am 9 (5): 1089-107, 1995.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  28. Duarte RF, Boumendil A, Onida F, et al.: Long-term outcome of allogeneic hematopoietic cell transplantation for patients with mycosis fungoides and Sézary syndrome: a European society for blood and marrow transplantation lymphoma working party extended analysis. J Clin Oncol 32 (29): 3347-8, 2014.[PUBMED Abstract]

  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.[PUBMED Abstract]

  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.[PUBMED Abstract]

  31. Kim YH, Tavallaee M, Sundram U, et al.: Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides and Sézary Syndrome With Variable CD30 Expression Level: A Multi-Institution Collaborative Project. J Clin Oncol 33 (32): 3750-8, 2015.[PUBMED Abstract]

  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.[PUBMED Abstract]

 | 

Key References for Mycosis Fungoides (Including Sézary Syndrome) Treatment

These references have been identified by members of the PDQ Adult Treatment Editorial Board as significant in the field of mycosis fungoides and Sézary 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 and SS. Listed after each reference are the sections within this summary where the reference is cited.


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Changes to This Summary (07/12/2017)

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 (MF) (Including Sézary Syndrome [SS])

Revised text to state that the cutaneous T-cell lymphomas should be distinguished from other T-cell lymphomas that involve the skin, such as anaplastic large cell lymphoma, peripheral T-cell lymphoma, adult T-cell leukemia/lymphoma, or subcutaneous panniculitic T-cell lymphoma.

Added Alberti-Violetti et al. as reference 9. Added text to state that the Cutaneous Lymphoma International Consortium retrospectively reviewed 1,275 patients and found four independent prognostic markers that indicate a worse survival, including stage IV disease, age older than 60 years, large cell transformation, and elevated lactate dehydrogenase (cited Scarisbrick et al. as reference 10).

Added R. Volmer as reference 12. Revised text to state that in contrast, more than 50% of patients with stage III through stage IV disease die of MF, with a median survival of approximately 5 years. Also added that 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 groups and advanced-stage groups (cited Benton et al. as reference 15).

Revised text to state that cutaneous disease can manifest itself as an eczematous patch or plaque stage covering less than 10% of the body surface, a plaque stage covering 10% or more of the body surface, or as tumors that frequently undergo necrotic ulceration. Also revised the text about several retrospective studies, which showed that 20% of patients progressed from stage I or II disease to stage III or IV disease (cited Wernham et al. as reference 19 and Desai et al. as reference 20).

Treatment Option Overview for MF (Including SS)

Added Olsen et al. as reference 4.

Added text to state that total-skin electron-beam radiation therapy can provide excellent palliation, with complete response rates of as much as 80%, and may be combined with systemic treatment. Also added ultraviolet B radiation or ultraviolet A radiation as radiation therapy options.

Added Targeted Therapy as a new subsection.

Added text to state that among these highly selected patients, the 5-year OS rate ranges from 30% to 50%, with a relapse-free survival rate of 15% to 25% (cited Lechowicz et al. as reference 50).

Stage I and Stage II MF

This section was extensively revised.

Stage III and Stage IV MF (Including SS)

This section was extensively revised.

Recurrent MF (Including SS)

Revised text to include allogeneic bone marrow or stem cell transplantation for the transplantation treatment option under clinical evaluation (cited Lechowich et al. as reference 30).

Added text to include brentuximab vedotin, a targeted therapy, as a treatment option under clinical evaluation (cited Kim et al. as reference 31 and Duvic et al. as reference 32).

Key References for MF (Including SS)Treatment

Editorial changes were made to this section.

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.

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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 Sézary 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:


  • be discussed at a meeting,

  • be cited with text, or

  • replace or update an existing article that is already cited.

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 Sézary 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.

    Permission to Use This Summary

    PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”

    The preferred citation for this PDQ summary is:

    PDQ® Adult Treatment Editorial Board. PDQ Mycosis Fungoides (Including Sézary 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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