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Immune response boost benefits patients with T-cell lymphoma.

NEW ORLEANS -- Normalizing the immune system with biologic response modifiers is perhaps the best hope for increasing disease-free intervals and improving quality of life for patients with cutaneous T-cell lymphoma.

Evidence supports the importance of a host antitumor immune response for controlling the progression of this disease, said Erin Boh, M.D., at a dermatology update sponsored by Tulane University.

"Early on in the disease, a number of cytotoxic T cells are trying to curb the proliferation of a malignant clone," said Dr. Boh, professor of dermatology at Tulane in New Orleans. "So, treatments with agents that upregulate the immune response have the best results."

However, there are no studies showing that even early, aggressive treatment prolongs survival, she noted.

Topical treatment is used in the early stages of the disease, but as the tumor grows, additional therapies must be implemented.

Denileukin diftitox has been very effective in treating cutaneous lymphoma; it causes rapid tumor lysis by inhibiting protein synthesis in cells that express the interleukin-2 receptor.

The drug is infused intravenously once a day for 5 days every 3 weeks. Infusion-site symptoms are common; patients who are hypoalbuminic may experience capillary leak syndrome leading to hypotension. After four to six treatment cycles, patients are maintained with bexarotene or PUVA, with or without interferon.

During treatment with bexarotene, it's important to monitor the lipid levels frequently. "The drug increases lipids incredibly," Dr. Boh said. "You have to pretreat with lipid-lowering drugs." Bexarotene also induces hypothyroidism, so thyroxine treatment is necessary.

Extracorporeal photopheresis has increased survival from an average of 24 months to 60 months. The combination of UVA and Oxsoralen normalizes the patient's T-cell phenotype balance. "You're developing more cytotoxic T cells that are then directed against the malignant clone," she said at the meeting, also sponsored by the International Academy of Cosmetic Dermatology.

Dr. Boh also mentioned two variants of the disease: subcutaneous panniculitis-like T-cell lymphoma and granulomatous slack skin.

The subcutaneous panniculitis-like variant is uncommon and usually occurs in young adults or even in children. It is characterized by fat necrosis, multiple subcutaneous nodules with fever, hepatosplenomegaly, mucosal ulcers, and serosal effusions. Biopsies of affected organs reveal extensive hemorrhage and histiocytes phagocytizing red blood cells. The prognosis is very poor with visceral involvement. "These patients do very poorly, and nothing really helps them," Dr. Boh said.

Granulomatous slack skin is a rare variant of cutaneous lymphoma. Patients exhibit large erythematous plaques in intertriginous or flexural areas. Histology shows dense granulomatous infiltrate with pleomorphic T cells and multinucleated giant cells. The elastin in the skin breaks down, resulting in circumscribed areas of pendulous lax skin.


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Title Annotation:Dermatology
Author:Sullivan, Michele G.
Publication:Internal Medicine News
Geographic Code:1USA
Date:Nov 1, 2004
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