Treatment of cutaneous T cell lymphoma: 2001.

The neoplastic cells of mycosis fungoides (MF) and Sézary syndrome are recognized to be clonal expansions of "memory" T cells that home into the upper dermis and epidermis via the interplay of adhesion molecules and chemokines, and this may account for the marked effectiveness and even curative potential of various skin-directed therapies utilized to treat clinically early disease. However, because neoplastic T cells freely circulate and are detectable in extracutaneous tissues by PCR prior to other methods, effective long-term control of more advanced MF and Sézary syndrome, i.e. reduction of tumor burden and decreased risk of transformation into aggressive lymphoma, often requires long-term administration of a therapy with systemic activity in addition to skin-directed therapies. Therapies with immunomodulatory activities, e.g. interferon alfa, bexarotene or extracorporeal photochemotherapy (ECP), are probably superior to traditional cytotoxic drugs in this regard although the response rates are relatively low. Selected patients with advanced or biologically aggressive CTCL should be considered for an allogeneic stem cell transplantation regimen to induce a graft-versus-tumor response. New and emerging treatments include immunotoxins such as denileukin diftitox that selectively target neoplastic T cells, potent immunomodulatory cytokines such as rIL-12 to enhance innate antitumor immune mechanisms, novel immunotherapeutic approaches that use dendritic cells loaded with tumor-associated antigens or vaccination using synthetic peptides or DNA plasmids that express the variable region of the T cell receptor beta chain, and possibly gene and protein transduction therapy to correct intracellular defects in neoplastic T cells. Overall the future of therapy for CTCL seems quite optimistic.