Mycosis fungoides treatment

Psoralens, or furocoumarins, are a class of heterocyclic aromatic compounds used in photochemotherapy treatment of a variety of skin diseases such as psoriasis, vitiligo, mycosis fungoides, polymorphous light eruption, and more [68-71]. The compounds are present in numerous plants throughout the world. In photoche-... 

Alternative/Adjunctive treatment Psoriasis, seborrheic dermatitis, severe diaper rash, dishidrosis, nodular prurigo, chronic discoid lupus erythematosus, alopecia areata, lymphocytic infiltration of the skin, mycosis fungoides, and familial benign pemphigus of Hailey-Hailey. 

Interferon alfa-2a Treatment of active, chronic hepatitis, bladder or renal carcinoma, malignant melanoma, multiple myeloma, mycosis fungoides, non-Hodgkin s lymphoma... 

Treatment of bladder, cervical, renal carcinoma, chronic myelocytic leukemia, laryngeal papillomatosis, multiple myeloma, mycosis fungoides... 

Information in humans is limited to reports of squamous eell carcinomas of the skin following therapeutic application of nitrogen mustard in the treatment of mycosis, fungoides, and psoriasis (lARC, 1987). 

Van Vloten, W.A., Cooijams, A.C.M., Poel, J., Meulemhelt, J. (1993). Concentrations of nitrogen mustard in the air during topical treatment of patients with mycosis fungoides. Br. J. Dermatol. 128 404-6. 

Of 22 patients, median age 61 years, who had received a median of three previous types of therapy for mycosis fungoides or Sezary syndrome and were given alemtuzumab in increasing doses (from 3 to 30 mg three times a week for 12 weeks), 11 had no infectious complications, one had fatal pulmonary aspergillosis 2.5 months after the end of treatment, and another contracted fatal Mycobacterium pneumonia 10 months after the end of treatment (7). 

Zackheim HS. Topical carmustine (BCNU) in the treatment of mycosis fungoides. Dermatol Ther 2003 16(4) 299-302. 

Photochemotherapy, which consists of oral (and sometimes topical) administration of psoralens (the furo-coumarins 5-methoxypsoralen, 8-methoxypsoralen, and trioxysalen) plus long-wave ultraviolet radiation, known as PUVA, is a well-established effective treatment for psoriasis, which has also been used for vitiligo (1), mycosis fungoides, alopecia areata, dyshidrotic eczema, atopic dermatitis, and certain other skin diseases. Guidelines for treatment have been recommended (2,3). 

Photosensitizers are agents that sensitize cells to radiation in the visible and near ultraviolet region of the radiation spectrum. Therapeutic use has been made of naturally occurring psoralens to treat vitiligo and psoriasis, in so-called photodynamic therapy. With newly developed UV irradiation systems that emit high-intensity UVA radiation, the principle has been extended to the treatment of severe psoriasis, mycosis fungoides and many other skin diseases. Agents used in psoralen photochemistry (PUVA) medicine include methoxypsoralen (8-MOP), trioxysalen and other synthetic psoralens. 

Mesna dose is typically 60-100% of ifosfamide dose (1 1 for continuous infusion ifosfamide) ifosfamide and mesna are physically compatible and may be delivered in same IV bag CNS toxicity and nausea and vomiting may be more severe with rapid infusion case reports suggest methylene blue may be effective treatment for CNS toxicity Antidote for extravasation sodium thiosulfate very short stability in aqueous solutions, about 1 hour Used as topical solution or in compounded ointments for mycosis fungoides... 

Linear psoralens have been extensively studied in the treatment of T-ceU lymphoma (mycosis fungoides, MF) [22,30-35]. Treatment of MF is indicated to reduce symptoms, improve cUnical appearance, prevent secondary complications, and prevent progression of disease, all of which may have an impact on survival. It has been reported that psoralen and ultraviolet A radiation is effective in early-stage MF, inducing complete remissions in most patients. Psoralens and ultraviolet A radiation may also be combined with low doses of interferon (IFN)-alpha to treat stage I/II disease. Extracorporeal photophere-sis may also be used successfully, but it is not generally available [31]. 

Cladribine, a purine nucleoside analog, with antineoplas-tic properties (0.09 mg/kg daily by continuous IV infusion for 7 days), is indicated in the treatment of active hairy cell leukemia. In addition, it has been used in advanced cutaneous T-cell lymphomas, chronic lymphocytic leukemia, non-Hodgkin s lymphomas, acute myeloid leukemias, autoimmune hemolytic anemia, mycosis fungoides, or Sezary syndrome (see also Figure 15). 

Uracil mustard, an alkylating agent with antineoplastic activity (1 to 2 mg p.o. daily for three months), is indicated in treatment of chronic lymphocytic and myelocytic leukemia Hodgkin s disease, non-Hodgkin s lymphomas of the histiocytic and lymphocytic types reticulum cell sarcoma lymphomas mycosis fungoides polycythemia vera and ovarian, cervical, and lung cancer. 

It is effective in Hodgkin s disease. Usual practice is to administer mechlorethamine with other antineoplastic agents such as vincristine, prednisone etc. It is the drug of choice for the treatment of mycosis fungoides and lymphomas. 

In addition to the hematologic indications that it shares with vincristine, vinblastine sulfate (Fig. 42.35) has found utility in the treatment of advanced testicular carcinoma (often in combination with bleomycin), advanced mycosis fungoides, Kaposi s sarcoma, and histiocytosis X. Leukopenia is the dose-limiting side effect, and dose reductions are warranted in patients with serum bilirubin levels greater than 3 mg/dL. The drug-related impact on erythrocyte and thrombocyte levels usually is insignificant. Like vincristine, it is administered as an IV bolus or infusion. The initial elimination half-life of 3.7 minutes is similar to vincristine, but the 24.8-hour terminal half-life is significantly shorter. 

Vinblastine sulfate is mainly used in association with other antineoplastic agents, in the treatment of Hodgkin s disease and other lymphomas including mycosis fungoides. 

Topical carmustine has been used for the treatment of mycosis fiingoides, lymphomatoid papulosis and parapsoriasis en plaques. Zackheim (1994) reported their experience of 172 patients with patch-plaque-stage mycosis fungoides treated with topical i,3-bis(2-chlo-roethyl)-i-nitrosourea solution. Complete blood counts were determined once each month during treatment. Mild, reversible myelosuppression occurred in less than 10% of patients using 20 mg/day total-body application and was rare in those using 10 mg/ day. 

Similarly, four patients with previously treatment-resistant mycosis fungoides (cutaneous T cell lymphoma) responded well to oral isotretinoin, 2-3 mg/kg/ day, with production of prolonged partial remission (Kessler et al., 1983). Tumors and plaques underwent near complete clearing. The skin lesions of cutaneous T cell lymphoma are characterized by epidermal infiltration with atypical mononuclear cells, mainly helper T cells but lower than normal numbers of killer T cells. In this regard, retinoic acid has been shown to enhance antigen-specific cytotoxic T cell activity (Dennett and Lotan, 1978), suggesting one immune mechanism by which retinoids could affect mycosis fungoides. 

PUVA is a psoralen+UV-A treatment for eczema, psoriasis, graft-versus-host disease, vitiligo, mycosis fungoides, large-plaque parapsoriasis and cutaneous T-cell lymphoma. The psoralen is applied or taken orally to sensitise the skin, and then the skin is exposed to UV A. The psoralens allow a relatively lower dose of UV A to be used. When they are combined with exposure to UV A in PUVA, they are highly effective at clearing psoriasis and vitiligo. 

Successful monotherapy of cutaneous T cell lymphoma has been reported with etretinate [56] as well as with isotretinoin [24, 41, 57, 79] and with arotinoid Ro 13-6298 [78]. However, a combination of etretinate/PUVA therapy (RePUVA) appeared to be more effective [59]. Jones and coworker [39] reported on the successful treatment of mycosis fungoides and Sezary syndrome with a combination of etretinate and electron beam therapy. 

Altomare GF, Capella GL, Pigatto PD, Finzi AF (1993) Intramuscular low dose alpha-2b interferon and etretinate for treatment of mycosis fungoides. Int J Dermatol 32 138-141... 

Braathen LR, McFadden N (1989) Successful treatment of mycosis fungoides with the combination of etretinate and human recombinant interferon alpha-2a. J Dermatol Treat 1 29-32... 

Fitzpatrick JE, Mellette JR (1986) Treatment of mycosis fungoides with isotretinoin. J Dermatol Surg Oncol 12 626-629... 

Hoting E, Paul E, Plewig G (1986) Treatment of rosacea with isotretinoin. Int J Dermatol 25 660-663 Imcke E, Ruszczak Zb, Mayer-da-Silva A, Detmar M, Orfanos CE (1991) Cultivation of human dermal microvascular endothelial cells in vitro Inununocytochemical and ultrastructural characterization and effect of treatment with three synthetic retinoids. Arch Dermatol Res 283 149-157 Jansen T, Plewig G (1997) Advances and perspectives in acne therapy. EurJ Med Res 28 321-334 Jones G, McLean J, Rosenthal D, Roberts J, Sander DN (1992) Combined treatment with oral etretinate and electron beam therapy in patients with cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome). J Am Acad Dermatol 26 960-967... 

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