Treatment of early stage (IA to IIA) mycosis fungoides
- Richard T Hoppe, MD
Richard T Hoppe, MD
- Professor of Radiation Oncology
- Stanford University School of Medicine
- Youn H Kim, MD
Youn H Kim, MD
- Professor of Dermatology
- Stanford University School of Medicine
- Steven Horwitz, MD
Steven Horwitz, MD
- Associate Attending
- Memorial Sloan-Kettering Cancer Center
- Section Editors
- Timothy M Kuzel, MD
Timothy M Kuzel, MD
- Section Editor — Lymphoproliferative Disorders
- Professor of Medicine
- Feinberg School of Medicine, Northwestern University
- John A Zic, MD
John A Zic, MD
- Section Editor — Cutaneous Lymphoma
- Associate Professor of Medicine/Dermatology
- Vanderbilt University School of Medicine
Mycosis fungoides (MF) is an extranodal, indolent non-Hodgkin lymphoma of T cell origin that primarily develops in the skin, but can ultimately involve the lymph nodes, blood, and visceral organs. Early stage (IA to IIA) disease consists of papules, patches, or plaques, with limited, if any, lymph node involvement and no visceral involvement (table 1A-B). Patients with limited skin involvement plus the more aggressive histopathologic findings of folliculotropism or transformed large cell variants and those with blood involvement are treated as more advanced disease. (See 'Special scenarios' below.)
The management of early stage mycosis fungoides (MF) will be discussed here. The management of more advanced stage MF and the more aggressive leukemic variant, Sézary syndrome, is presented separately as are the clinical presentation, diagnosis, staging, and prognosis of MF and Sézary syndrome. (See "Treatment of advanced stage (IIB to IV) mycosis fungoides" and "Clinical manifestations, pathologic features, and diagnosis of mycosis fungoides" and "Treatment of Sézary syndrome".)
The standard staging system for mycosis fungoides (MF) is based upon an evaluation of the skin (T), lymph nodes (N), visceral involvement (M), and blood (B) (table 1A-B and table 2) . Details are presented separately. (See "Staging and prognosis of mycosis fungoides and Sézary syndrome", section on 'Staging'.)
STAGE IA DISEASE
Overview — Stage IA disease includes those patients with patches, plaques, or papules that involve less than 10 percent of the total skin surface with no involvement of lymph nodes or viscera (table 1A-B). Patients with stage IA disease who also have greater than 5 percent circulating atypical (Sézary) cells (ie, those with B1 disease), histologic evidence of the folliculotropic variant, or large cell transformed mycosis fungoides (MF) are treated with more aggressive therapy. (See 'Special scenarios' below.)
Patients with stage IA disease are treated with skin directed therapies. A randomized trial demonstrated that early aggressive therapy with combination chemotherapy plus electron-beam radiation therapy does not appear to improve survival when compared with the use of sequential topical regimens .
- 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 2007; 110:1713.
- 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 1989; 321:1784.
- Zackheim HS, Kashani-Sabet M, Amin S. Topical corticosteroids for mycosis fungoides. Experience in 79 patients. Arch Dermatol 1998; 134:949.
- Zackheim HS. Treatment of patch-stage mycosis fungoides with topical corticosteroids. Dermatol Ther 2003; 16:283.
- Kim YH, Martinez G, Varghese A, Hoppe RT. Topical nitrogen mustard in the management of mycosis fungoides: update of the Stanford experience. Arch Dermatol 2003; 139:165.
- Kim YH, Jensen RA, Watanabe GL, et al. Clinical stage IA (limited patch and plaque) mycosis fungoides. A long-term outcome analysis. Arch Dermatol 1996; 132:1309.
- Ramsay DL, Halperin PS, Zeleniuch-Jacquotte A. Topical mechlorethamine therapy for early stage mycosis fungoides. J Am Acad Dermatol 1988; 19:684.
- Vonderheid EC, Tan ET, Kantor AF, et al. Long-term efficacy, curative potential, and carcinogenicity of topical mechlorethamine chemotherapy in cutaneous T cell lymphoma. J Am Acad Dermatol 1989; 20:416.
- 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 2013; 149:25.
- Ramsay DL, Meller JA, Zackheim HS. Topical treatment of early cutaneous T-cell lymphoma. Hematol Oncol Clin North Am 1995; 9:1031.
- Price NM, Hoppe RT, Deneau DG. Ointment-based mechlorethamine treatment for mycosis fungoides. Cancer 1983; 52:2214.
- Abel EA, Sendagorta E, Hoppe RT. Cutaneous malignancies and metastatic squamous cell carcinoma following topical therapies for mycosis fungoides. J Am Acad Dermatol 1986; 14:1029.
- Smoller BR, Marcus R. Risk of secondary cutaneous malignancies in patients with long-standing mycosis fungoides. J Am Acad Dermatol 1994; 30:201.
- Lindahl LM, Fenger-Grøn M, Iversen L. Secondary cancers, comorbidities and mortality associated with nitrogen mustard therapy in patients with mycosis fungoides: a 30-year population-based cohort study. Br J Dermatol 2014; 170:699.
- Zackheim HS, Epstein EH Jr, Crain WR. Topical carmustine (BCNU) for cutaneous T cell lymphoma: a 15-year experience in 143 patients. J Am Acad Dermatol 1990; 22:802.
- Zackheim HS. Topical carmustine (BCNU) in the treatment of mycosis fungoides. Dermatol Ther 2003; 16:299.
- Breneman D, Duvic M, Kuzel T, et al. Phase 1 and 2 trial of bexarotene gel for skin-directed treatment of patients with cutaneous T-cell lymphoma. Arch Dermatol 2002; 138:325.
- 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 2003; 49:801.
- Duvic M, Lemak NA, Redman JR, et al. Combined modality therapy for cutaneous T-cell lymphoma. J Am Acad Dermatol 1996; 34:1022.
- Thomsen K, Hammar H, Molin L, Volden G. Retinoids plus PUVA (RePUVA) and PUVA in mycosis fungoides, plaque stage. A report from the Scandinavian Mycosis Fungoides Group. Acta Derm Venereol 1989; 69:536.
- Jones G, McLean J, Rosenthal D, et al. Combined treatment with oral etretinate and electron beam therapy in patients with cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome). J Am Acad Dermatol 1992; 26:960.
- Apisarnthanarax N, Talpur R, Ward S, et al. Tazarotene 0.1% gel for refractory mycosis fungoides lesions: an open-label pilot study. J Am Acad Dermatol 2004; 50:600.
- Jones GW, Hoppe RT, Glatstein E. Electron beam treatment for cutaneous T-cell lymphoma. Hematol Oncol Clin North Am 1995; 9:1057.
- Jones GW, Kacinski BM, Wilson LD, et al. Total skin electron radiation in the management of mycosis fungoides: Consensus of the European Organization for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Project Group. J Am Acad Dermatol 2002; 47:364.
- Cotter GW, Baglan RJ, Wasserman TH, Mill W. Palliative radiation treatment of cutaneous mycosis fungoides--a dose response. Int J Radiat Oncol Biol Phys 1983; 9:1477.
- Neelis KJ, Schimmel EC, Vermeer MH, et al. Low-dose palliative radiotherapy for cutaneous B- and T-cell lymphomas. Int J Radiat Oncol Biol Phys 2009; 74:154.
- 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 2013; 85:747.
- Ramsay DL, Lish KM, Yalowitz CB, Soter NA. Ultraviolet-B phototherapy for early-stage cutaneous T-cell lymphoma. Arch Dermatol 1992; 128:931.
- Resnik KS, Vonderheid EC. Home UV phototherapy of early mycosis fungoides: long-term follow-up observations in thirty-one patients. J Am Acad Dermatol 1993; 29:73.
- Gathers RC, Scherschun L, Malick F, et al. Narrowband UVB phototherapy for early-stage mycosis fungoides. J Am Acad Dermatol 2002; 47:191.
- Herrmann JJ, Roenigk HH Jr, Hurria A, et al. Treatment of mycosis fungoides with photochemotherapy (PUVA): long-term follow-up. J Am Acad Dermatol 1995; 33:234.
- Hönigsmann H, Brenner W, Rauschmeier W, et al. Photochemotherapy for cutaneous T cell lymphoma. A follow-up study. J Am Acad Dermatol 1984; 10:238.
- Abel EA, Sendagorta E, Hoppe RT, Hu CH. PUVA treatment of erythrodermic and plaque-type mycosis fungoides. Ten-year follow-up study. Arch Dermatol 1987; 123:897.
- Roenigk HH Jr, Kuzel TM, Skoutelis AP, et al. Photochemotherapy alone or combined with interferon alpha-2a in the treatment of cutaneous T-cell lymphoma. J Invest Dermatol 1990; 95:198S.
- Pabsch H, Rütten A, Von Stemm A, et al. Treatment of childhood mycosis fungoides with topical PUVA. J Am Acad Dermatol 2002; 47:557.
- Diederen PV, van Weelden H, Sanders CJ, et al. Narrowband UVB and psoralen-UVA in the treatment of early-stage mycosis fungoides: a retrospective study. J Am Acad Dermatol 2003; 48:215.
- Carter J, Zug KA. Phototherapy for cutaneous T-cell lymphoma: online survey and literature review. J Am Acad Dermatol 2009; 60:39.
- 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 2016; 74:27.
- Boztepe G, Sahin S, Ayhan M, et al. Narrowband ultraviolet B phototherapy to clear and maintain clearance in patients with mycosis fungoides. J Am Acad Dermatol 2005; 53:242.
- 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 2005; 141:305.
- British Photodermatology Group guidelines for PUVA. Br J Dermatol 1994; 130:246.
- Kim YH, Chow S, Varghese A, Hoppe RT. Clinical characteristics and long-term outcome of patients with generalized patch and/or plaque (T2) mycosis fungoides. Arch Dermatol 1999; 135:26.
- Whittaker S, Ortiz P, Dummer R, et al. Efficacy and safety of bexarotene combined with psoralen-ultraviolet A (PUVA) compared with PUVA treatment alone in stage IB-IIA mycosis fungoides: final results from the EORTC Cutaneous Lymphoma Task Force phase III randomized clinical trial (NCT00056056). Br J Dermatol 2012; 167:678.
- 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 1995; 13:257.
- Chiarion-Sileni V, Bononi A, Fornasa CV, et al. Phase II trial of interferon-alpha-2a plus psolaren with ultraviolet light A in patients with cutaneous T-cell lymphoma. Cancer 2002; 95:569.
- Jones GW, Tadros A, Hodson DI, et al. Prognosis with newly diagnosed mycosis fungoides after total skin electron radiation of 30 or 35 GY. Int J Radiat Oncol Biol Phys 1994; 28:839.
- 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 1997; 38:1027.
- 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 2004; 58:1128.
- Kamstrup MR, Specht L, Skovgaard GL, Gniadecki R. A prospective, open-label study of low-dose total skin electron beam therapy in mycosis fungoides. Int J Radiat Oncol Biol Phys 2008; 71:1204.
- Hoppe RT. Total skin electron beam therapy in the management of mycosis fungoides. Front Radiat Ther Oncol 1991; 25:80.
- Specht L, Dabaja B, Illidge T, et al. Modern radiation therapy for primary cutaneous lymphomas: field and dose guidelines from the International Lymphoma Radiation Oncology Group. Int J Radiat Oncol Biol Phys 2015; 92:32.
- Lloyd S, Chen Z, Foss FM, et al. Acute toxicity and risk of infection during total skin electron beam therapy for mycosis fungoides. J Am Acad Dermatol 2013; 69:537.
- Demierre MF, Taverna J. Mirtazapine and gabapentin for reducing pruritus in cutaneous T-cell lymphoma. J Am Acad Dermatol 2006; 55:543.
- Duval A, Dubertret L. Aprepitant as an antipruritic agent? N Engl J Med 2009; 361:1415.
- PRETREATMENT EVALUATION
- STAGE IA DISEASE
- Topical corticosteroids
- - Topical corticosteroid administration
- - Topical corticosteroid toxicities
- Topical nitrogen mustard (HN2)
- - HN2 administration
- - HN2 toxicities
- Topical carmustine (BCNU)
- - BCNU administration
- - BCNU toxicities
- Topical retinoids
- - Bexarotene administration
- - Bexarotene toxicities
- Radiation therapy
- - Electron beam therapy
- - UVB
- - PUVA
- STAGE IB/IIA DISEASE
- Topical nitrogen mustard
- Total skin electron beam therapy
- - TSEBT administration
- - TSEBT toxicities
- SPECIAL SCENARIOS
- Folliculotropic variant
- Large cell transformation
- Blood involvement
- SUMMARY AND RECOMMENDATIONS