eMedicine Specialties > Dermatology > Lymphoma and Related Processes
Cutaneous T-Cell Lymphoma: Treatment & Medication
Updated: Nov 10, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
- When mycosis fungoides (MF) is confined to the skin (cutaneous T-cell lymphoma [CTCL]), skin-targeted therapies such as topical corticosteroids, heliotherapy, photochemotherapy (eg, psoralen plus UV-A [PUVA]), topical application of nitrogen mustard (mechlorethamine) or carmustine (BCNU), or radiotherapy, including total skin electron beam irradiation, are often effective a controlling manifestations.49 Bexarotene is also sometimes used for disease confined to the skin. Psoriatic doses of methotrexate have been used, but some concern exists relating to large cell transformation occasionally observed in these patients.
- Treatment of stages T1 and T2 MF with total skin electron beam therapy is highly effective in early-stage MF without adjuvant therapy. Management of relapses with local radiotherapy or a second round of total skin electron beam irradiation is feasible, timesaving, and cost-effective.50 In patients with limited patch-stage MF, topical steroids or bexarotene gel can be used.
- Tazarotene, long-term and low-dose oral etoposide, and imiquimod may be of value in the treatment of early CTCL.51,52 One small pilot study showed tazarotene 0.1% gel to be a well-tolerated and effective adjuvant topical therapy for the treatment of refractory MF.53
- Biological agents such as interferon alfa and other cytokines (eg, interleukin 2 [IL-2]), traditional and new retinoids such as bexarotene, and receptor-targeted cytotoxic fusion proteins (eg, DAB389I-2; denileukin diftitox) are increasingly being used. Combination therapy with bexarotene and PUVA should be considered for patients with treatment-resistant CTCL refractory to monotherapy.54 However, the precise use of these new treatments, either as single-agent therapy or in combination with other therapies (eg, PUVA) in the treatment of MF, remains to be established.
- Multiagent chemotherapy is used with unequivocal lymph node or systemic involvement or in cases with widespread tumor-stage MF that is refractory to skin-targeted therapies and is not early patch/plaque-stage disease.
- Perifollicular localization of the dermal infiltrates in FMF is often less responsive to skin-targeted therapies (eg, PUVA, topical nitrogen mustard) than classic plaque-stage MF, and total skin electron beam irradiation is superior.55 However, because sustained complete remissions are rarely achieved with electron beam therapy, PUVA combined with retinoids or interferon alfa should be considered, although persistent tumors can be effectively treated with local radiotherapy. Follicular CTCL may benefit from isotretinoin for persistent cysts and comedones.56 Early syringotropic CTCL may be treated with local radiotherapy, with excellent local control.57
- Extracorporeal photopheresis, either alone or in combination with other treatment modalities (eg, interferon alfa), is an effective treatment for SS and erythrodermic MF, with overall response rates of 30-80% and complete response rates of 14-25%.58 The alleged superiority of extracorporeal photopheresis over the traditional low-dose chemotherapy regimens has not been proven. Beneficial results have also been described with interferon alfa, either alone or in combination with PUVA therapy, prolonged treatment with a combination of low-dose chlorambucil (2-4 mg/d) and prednisone (10-20 mg/d), or with methotrexate (MTX) (5-25 mg/wk), but complete responses are uncommon. Skin-directed therapies such as PUVA or potent topical steroids are good adjuvant therapies. Beneficial effects of bexarotene and alemtuzumab (anti-CD52) have been noted, but the long-term effects of these therapies remain to be established.59
- Unrelated cord blood transplantation is a possible therapeutic option.60 In one patient, it was given following myeloablative conditioning, which brought a complete remission. Although a relapse occurred 3 months later, discontinuation of immune suppressant therapy led to MF regression and a second complete remission that continued for more than 23 months.
Surgical Care
Localized MF may benefit from a number of therapeutic modalities, including radiotherapy, intralesional steroids, or surgical excision. One option is to excise a patch or plaque with a 0.5-cm margin and then control subsequent disease with either irradiation or photochemotherapy with PUVA, photodynamic therapy, or carbon dioxide laser surgery.61 Localized radiation or a surgical approach to localized MF can be used, with the latter having the advantage that a full dose of radiation can be delivered in the same location at a later time, thus preserving options for future therapy.
Medication
Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of entities. One should distinguish indolent, low-risk mycosis fungoides (MF) and SS from aggressive HTLV-1–associated ATLL.62 Treatment for early-stage CTCL includes topical therapies with or without interferon alfa or oral agents, while advanced-stage patients often progress and are treated with chemotherapy and novel agents. Multiagent cytotoxic regimens may be palliative, but they seem to lack a demonstrated survival benefit.63
Novel therapies for CTCL include bexarotene, which has demonstrated efficacy in advanced refractory CTCL. Other novel agents include the IL-2 fusion toxin (Ontak), IL-12, pentostatin (a potent adenosine deaminase inhibitor), histone deacetylase inhibitors (eg, depsipeptide), NF-kappa-B inhibitors, cytokine-receptor antagonists, immunomodulatory therapies, and allogeneic stem cell therapy. The value of new therapeutic approaches to CTCL needs to be critically assessed in regard to overall survival and disease-specific survival.
Chemotherapy agents
Inhibit neoplastic growth.
Chlorambucil (Leukeran)
Alkylates and cross-links strands of DNA, inhibiting DNA replication and RNA transcription.
Adult
0.1-0.2 mg/kg/d PO or 3-6 mg/m2/d PO for 3-6 wk; adjust dose depending on blood cell counts or combine in low dose (2-4 mg/d) with prednisone (10-20 mg/d) or MTX (5-25 mg/wk) for SS
Pediatric
Not established for SS
0.1-0.2 mg/kg/d PO or 4.5 mg/m2/d for 3-6 wk; adjust dose depending on blood cell counts
None reported
Documented hypersensitivity; previous resistance to medication
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in history of seizure disorders or patients diagnosed with bone marrow suppression
Vorinostat (Zolinza)
Histone deacetylase (HDAC) inhibitor. HDAC inhibition results in hypoacetylation of core nucleosomal histones, condenses chromatin structure, and represses gene transcription. Indicated for treatment of progressive, persistent, or recurrent CTCL.
Adult
400 mg PO qd with food; if intolerant to therapy, may decrease dose to 300 mg PO qd; if necessary, further reduce to 300 mg PO qd for 5 consecutive days qwk
Pediatric
Not established
Coadministration with other HDAC inhibitors (eg, valproic acid) has caused severe thrombocytopenia and GI bleeding; coadministration with warfarin prolongs PT and INR
None known
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Common adverse effects include diarrhea, nausea, anorexia, weight loss, vomiting, and constipation (antiemetics, antidiarrheals, or fluid and electrolyte replacement may be required to prevent dehydration); also commonly causes fatigue or chills; pulmonary embolism and deep vein thrombosis have been reported; dose-related thrombocytopenia and anemia have occurred (may require dose reduction or discontinuance); may cause hyperglycemia; data limited on effect on QTc (monitor potassium, magnesium, and calcium levels and perform periodic ECGs); data limited in patients with renal or hepatic insufficiency
Methotrexate (Trexall)
Folic acid antagonist inhibits dihydrofolate reductase, an enzyme needed to make DNA.
Adult
5-25 mg/wk, with interferon alfa
Pediatric
Not established
Oral aminoglycosides may decrease absorption and blood levels of concurrent oral MTX; charcoal lowers MTX levels; coadministration with etretinate may increase hepatotoxicity of MTX; folic acid or its derivatives contained in some vitamins may decrease response to MTX
Probenecid, NSAIDs, salicylates, procarbazine, and sulfonamides (including TMP-SMZ) can increase MTX plasma levels; may decrease phenytoin plasma levels; may increase plasma levels of thiopurines
Documented hypersensitivity; alcoholism; hepatic insufficiency; documented immunodeficiency syndromes; preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia); renal insufficiency
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Monitor CBC counts monthly and liver and renal function q1-3mo during therapy (monitor more frequently during initial dosing, dose adjustments, or when risk of elevated MTX levels (eg, dehydration); has toxic effects on hematologic, renal, GI, pulmonary, and neurologic systems; discontinue if significant drop in blood cell counts occurs; fatal reactions reported when administered concurrently with NSAIDs
Etoposide (VePesid, Toposar)
Inhibits topoisomerase II and causes DNA strand breakage, resulting in arrest of cell proliferation in late S or early G2 portion of cell cycle.
Adult
100 mg/m2 IV for days 1-5
Pediatric
Not established
May prolong effects of warfarin and increase clearance of MTX; cyclosporine and etoposide have additive effects in cytotoxicity of tumor cells
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Bleeding and severe myelosuppression may occur
Romidepsin (Istodax)
Histone deacetylase (HDAC) inhibitor. Indicated for cutaneous T-cell lymphoma in patients who have received at least 1 prior systemic therapy.
Adult
14 mg/m2 IV infused over 4 h on days 1, 8, and 15 of 28-d cycle
Treatment discontinuation or interruption with or without dose reduction to 10 mg/m2 may be required to manage adverse effects
Pediatric
Not established
Binds to estrogen and may reduce effectiveness of estrogen-containing contraceptives; may increase effect of warfarin (prolonged PT, increased INR) when coadministered; coadministration with other drugs that prolong QT interval (eg, sotalol, dofetilide, erythromycin) may increase risk for serious arrhythmias
Strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) may increase serum levels
Potent CYP3A4 inducers (eg, dexamethasone, carbamazepine, phenytoin, rifampin, rifabutin, rifapentine, phenobarbital, St. John's wort) may decrease serum levels
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Common adverse effects include nausea, vomiting, anorexia fatigue, infections, anemia, thrombocytopenia, and leukopenia; may prolong QT interval and induce arrhythmias (monitor electrolyte [potassium, magnesium]) levels; monitor ECG in patients at risk for arrhythmia (eg, congenital long QT syndrome, history of significant cardiovascular disease, coadministration of drugs that significantly prolong QT interval)
Fusion proteins
Denileukin diftitox (Ontak)
Fusion protein (amino acid sequence of diphtheria linked to IL-2 amino acid sequence) that selectively delivers cytotoxic activity of diphtheria toxin to targeted cells. Used only in T-cell lymphoma whose malignant cells express CD25 component of IL-2 receptor. Interacts with high-affinity IL-2 receptor on surface of malignant cells to inhibit intracellular protein synthesis, which, in turn, causes cell death.
Adult
9-18 mcg/kg/d IV for 5 consecutive days administered q21d; duration of treatment not established; <2% response rate reported if no response by fourth cycle
Pediatric
Not established
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May impair immune function; associated with delayed-onset vascular leak syndrome (may occur within first 2 wk of infusion and persist or worsen after cessation); preexisting low serum albumin level may predispose or predict vascular leak syndrome; caution in preexisting cardiovascular disease and age >65 y; edema, hypotension, tachycardia, chest pain, headache, pain, nervousness, dizziness, hypocalcemia, and weight loss may occur
Bexarotene gel (Targretin Gel)
X-receptor–specific retinoid. May inhibit sebaceous gland differentiation and abnormal keratinization. Retinoid X-receptor–selective agonist.
Adult
1% gel qd qod for first week, then qd for 1 wk, then increase to up to qid
Pediatric
Not established
Pregnancy, documented hypersensitivity to medication or its class, vitamin A supplementation, diabetes mellitus if on insulin, or in patients taking gemfibrozil
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Bexarotene (Targretin)
An X-receptor–specific retinoid. May inhibit sebaceous gland differentiation and abnormal keratinization.
Adult
300 mg/m2/d PO single dose w/meal; may be given with PUVA for treatment of resistant CTCL
Pediatric
Not established
On basis of metabolism of bexarotene by cytochrome P-450 3A4, ketoconazole, itraconazole, erythromycin, gemfibrozil, grapefruit juice, and other inhibitors of cytochrome P-450 3A4 may increase serum levels; rifampin, phenytoin, phenobarbital, and other inducers of cytochrome P-450 3A4 may reduce plasma; caution when administering to patients using insulin, agents enhancing insulin secretion, or insulin sensitizers (may enhance their action)
Documented hypersensitivity; uncontrolled hyperlipidemia or hypothyroidism before drug initiation; do not administer to patients with risk factors for pancreatitis
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
When used in women of childbearing potential, obtain a negative pregnancy test 1 wk prior to therapy and monthly thereafter; instruct women of childbearing potential to use 2 reliable forms of contraception simultaneously, unless abstinence is the chosen method of contraception, for 1 mo prior, during, and 1 mo following discontinuation of drug; instruct male patients with sexual partners who are pregnant or have childbearing potential to use condoms during sexual intercourse while taking the drug and 1 mo afterward; perform fasting blood lipid determinations before therapy is initiated and qwk until lipid response to drug is established; obtain and serially monitor baseline CBC counts, liver function, and thyroid function tests; advise patients to limit vitamin A supplements and minimize exposure to sunlight and artificial UV
Biological response modulators
Immunomodulator/biologic agents.
Interferon alfa-2a (Intron-A)
Protein product manufactured by recombinant DNA technology. Mechanism of antitumor activity is not clearly understood; however, direct antiproliferative effects against malignant cells and modulation of host immune response may play important roles.
Adult
Induction: 36 million U/d for 10-12 wk IM/SC
Maintenance: 36 million U 3 times/wk IM/SC (may escalate dose to 3-9-18 million U qd over 3 consecutive days followed by 36 million U/d for remaining 10-12 wk)
Pediatric
Not established
Theophylline may increase toxicity by reducing clearance; cimetidine may increase antitumor effects; zidovudine and vinblastine may increase toxicity
Documented hypersensitivity; avoid in patients who have anaphylactic sensitivity to mouse immunoglobulin (IgG), egg protein, or neomycin; autoimmune hepatitis
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Depression and suicidal ideation may be adverse effects of treatment; infrequently, severe or fatal GI hemorrhage reported in association with therapy
Regarding bone marrow suppression, prior to initiation of therapy, perform tests to quantitate peripheral blood hemoglobin, platelets, granulocytes, hairy cells, and bone marrow hairy cells
Monitor patient periodically (eg, monthly) during treatment to determine response to treatment; if patient does not respond within 6 mo, discontinue treatment; if response occurs, continue treatment until no further improvement observed (not known whether continued treatment after that time is beneficial)
Antineoplastic agents
Monoclonal antibody against antigen on T cells.
Alemtuzumab (Campath)
Monoclonal antibody against CD52, an antigen found on B cells, T cells, and almost all CLL cells. Binds to CD52 receptor of lymphocytes, which slows proliferation of leukocytes
Adult
3-10 mg IV over 2 h initially; titrate slowly to 30 mg and administer 3 times/wk for up to 12 wk if no adverse effects
Pediatric
Not established
May increase virulence of live viral vaccines
Documented hypersensitivity; active systemic infections; underlying immunodeficiency (eg, AIDS)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May cause pancytopenia, thrombocytopenia, autoimmune hemolytic anemia, and serious infusion reactions (premedicate with acetaminophen, diphenhydramine, and hydrocortisone, and gradually increase dose); fatal bacterial, viral, fungal, and protozoan infections reported; hypotension may occur with IV administration (can control by discontinuing or slowing rate of infusion); antibody is not selective for cancerous B cells and T cells and may eradicate all normal lymphocytes of B- and T-cell lineage (resulting lymphopenia; risk of infection can be profound and long-lasting); posttransplant lymphoproliferative disorders, nausea, and diarrhea may occur
Topical chemotherapy agents
Topical carmustine (BCNU)
Alkylates and cross-links DNA strands, inhibiting cell proliferation.
Adult
Solution: 100 mg in 50 mL of 95% ethanol, then 5 mL solution mixed with 60 mL tap water and applied qd
Ointment: 100 mg in 50 mL 95% ethanol, then 20-40 mg mixed with 100 g of petrolatum and applied qd
Pediatric
Not established
Coadministration with cimetidine may increase toxicity; coadministration with etoposide may cause severe hepatic dysfunction (hyperbilirubinemia, ascites, and thrombocytopenia)
Documented hypersensitivity; myelosuppression from previous chemotherapy; pregnancy
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in patients with depressed platelet, leukocyte, or erythrocyte count or with hepatic or renal impairment; perform baseline pulmonary function tests
Mechlorethamine solution or ointment (Mustargen)
Topical nitrogen mustard. Alkylating agent that inhibits DNA replication.
Adult
Topical aqueous solution: 10 mg in 60 mL tap water applied qd
Topical ointment: 10 mg in 10 mL 95% absolute alcohol, then mixed with 100 g white petrolatum and applied qd
Pediatric
Not established
None reported
Documented hypersensitivity to medication or its class of drugs; pregnancy
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Delayed hypersensitivity (35-60%) can be overcome with use of topical steroids or desensitization; less common with use of ointment; associated with an increased risk of nonmelanoma skin cancers
Topical immune response modifiers
Imiquimod 5% cream (Aldara)
Binds to Toll-like receptors 7 and 8 and induces secretion of interferon alfa and other cytokines; mechanism of action unknown.
Adult
Apply qd
Pediatric
Not established
None reported
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Retinoids
Regulate genes that control cellular differentiation and proliferation.
Alitretinoin (Panretin)
Naturally occurring endogenous retinoid. Inhibits growth of Kaposi sarcoma by binding to retinoid receptors.
Adult
0.1% gel: Apply topically bid/qid to affected cutaneous lesions
Pediatric
Not established
Increases toxicity of DEET if used concurrently
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Preexisting CTCL; do not use occlusive dressing; avoid UV light exposure of treated areas
Tazarotene gel (Avage, Tazorac)
Retinoid prodrug whose active metabolite modulates differentiation and proliferation of epithelial tissue; may also have anti-inflammatory and immunomodulatory properties.
Adult
Apply thin film qd to cover lesion (2 mg/cm2); not to exceed >20% of BSA
Pediatric
Children: Not established
Adolescents: Administer as in adults
None reported
Documented hypersensitivity
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
May cause burning or stinging sensations; discontinue if excessive irritation; rinse thoroughly if contact with eyes, eyelids, or mouth; may cause severe irritation in eczematous skin; photosensitivity may occur
Steroids
Prednisone (Deltasone)
Immunosuppressant; should be used together with other agents such low-dose chlorambucil and interferon alfa.
Adult
10-20 mg/d with low-dose chlorambucil and interferon alfa
Pediatric
Not established for this usage
Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Documented hypersensitivity; viral infection, peptic ulcer disease, hepatic dysfunction, connective-tissue infections, and fungal or tubercular skin infections; GI bleeding or ulceration
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Abrupt discontinuation of may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use
More on Cutaneous T-Cell Lymphoma |
| Overview: Cutaneous T-Cell Lymphoma |
| Differential Diagnoses & Workup: Cutaneous T-Cell Lymphoma |
 Treatment & Medication: Cutaneous T-Cell Lymphoma |
| Follow-up: Cutaneous T-Cell Lymphoma |
| Multimedia: Cutaneous T-Cell Lymphoma |
| References |
| « Previous Page | Next Page » |
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Further Reading
Keywords
CTCL, mycosis fungoides, patch stage mycosis fungoides, large plaque parapsoriasis, plaque stage mycosis fungoides, tumor stage mycosis fungoides, d'emblee mycosis fungoides, primary cutaneous pleomorphic mycosis fungoides, medium-sized T-cell lymphoma, large cell CD30+ T-cell lymphoma, large cell CD30- T-cell lymphomas, solitary mycosis fungoides, unilesional mycosis fungoides, unilesional pagetoid reticulosis, Woringer-Kolopp disease, follicular mycosis fungoides, Sézary syndrome, Sezary syndrome, Sezary's syndrome, erythrodermic mycosis fungoides, granulomatous slack skin, granulomatous CTCL, granulomatous mycosis fungoides, angiocentric CTCL, subcutaneous CTCL, panniculitis-like CTCL, panniculitislike CTCL, lipotropic CTCL, panniculotropic CTCL, subcutaneous mycosis fungoides, suppressor T-cell CTCL, CD8+ CTCL, delta/gamma CTCL, NK cell CTCL, natural killer CTCL, KI-1+ large cell CTCL
