ONCOLOGY Vol 21 No 2_Suppl_1 | Oncology

Cutaneous T-Cell Lymphoma: Molecular and Cytogenetic Findings

February 01, 2007

Chromosomal changes have been identified early in the disease process in cutaneous T-cell lymphoma (CTCL): both losses and gains of chromatin have been found on several chromosomes. The extent of chromosomal aberrations increases with disease stage and in more aggressive subtypes of the disorder. Changes in specific genes, such as NAV3, have been characterized in patients with CTCL, and may produce a proliferation advantage for affected cells. In addition, the expression of some genes can discriminate between controls and patients with CTCL. Therefore, the over- or under-expression of certain genes may be of diagnostic and pathogenic relevance in this disease, and may allow the development of selective treatments.

The Pathology of Cutaneous T-Cell Lymphoma

February 01, 2007

The diagnosis of cutaneous T-cell lymphoma (CTCL) requires accurate histopathology, including immunocytochemistry, as well as careful clinical appraisal and analysis for T-cell clonality. This paper reviews the key histologic features of mycosis fungoides (MF) and its variants, and of lymphomatoid papulosis (LyP). Mycosis fungoides is an epidermotropic CTCL that evolves through distinct disease stages of patch, plaque, and tumor, often leading to transformation in the final stages. Disease staging is made clinically, and diagnosis may be difficult during the early stages because several common dermatologic conditions share features with MF. Therefore, clinical appraisal plus the presence of characteristic histopathologic features are needed to ensure accurate diagnosis. Clinical information is particularly important in the diagnosis of LyP, as the disease appears malignant histologically, but has a benign clinical course. Several other T-cell lymphomas were defined in a recent classification of these cutaneous lymphomas, and some key features of these disorders are also briefly reviewed.

Optimal Combination With PUVA: Rationale and Clinical Trial Update

February 01, 2007

Cutaneous T-cell lymphoma (CTCL) is relatively benign in its early stages, but survival rates decrease dramatically as the disease progresses. As no curative therapies are currently available, the goal of therapy is preventing or delaying progression from early disease stages while minimizing long-term toxicity. No single agent, including psoralen plus ultraviolet A (PUVA), can control disease progression fully, so combination therapy is needed to improve response rates. In addition, low-dose combination therapy may improve treatment safety and tolerability. A combination of PUVA and interferon (IFN)α in early disease has been shown to be effective and well tolerated. Likewise, small studies of PUVA and bexarotene (Targretin) indicate good efficacy for this combination. Reduced doses of these combinations may also be effective as maintenance therapies following complete remission. Other treatment combinations shown to be effective in early disease stages include bexarotene with IFNα, and bexarotene with denileukin diftitox (Ontak). In advanced stages of CTCL, liposomal-encapsulated doxorubicin or extracorporeal photopheresis may be combined with bexarotene or IFNα.

Is There a Role for Hemopoietic Stem-Cell Transplantation in CTCL?

February 01, 2007

The role of autologous and allogeneic stem-cell transplantation (SCT) in the treatment of cutaneous T-cell lymphoma (CTCL) is reviewed. Patients most likely to benefit are those with advanced-stage disease, multiple relapses, and short remissions; chemosensitive disease is also a prerequisite for these treatments. Autologous SCT produces high response rates in patients with peripheral T-cell lymphoma, but these are generally of short duration. This therapy is relatively safe to administer, with little transplant-related mortality. In contrast, allogeneic SCT may be highly toxic and result in transplant-related mortality, but it has the potential to produce long-lasting responses. Prospective studies of these treatments in patients with CTCL are required. Nevertheless, selected patients could be considered for allogeneic SCT, preferably early in their disease when their performance status is still good.

Choices in the Treatment of Cutaneous T-Cell Lymphoma

February 01, 2007

Mycosis fungoides is responsive to treatment in the early stages; patients have a long duration of survival but are rarely cured of the disease. Therefore, patients require long-term, sequential therapies with as little toxicity as possible. In the early stages, skin-directed therapies, such as psoralen plus ultraviolet A in combination with retinoids or interferon, generally produce good, long-term responses. Once the disease progresses, systemic agents such as cytokines and retinoids are introduced. The cytokines provide a rational treatment approach for cutaneous T-cell lymphoma (CTCL) and produce good, long-lasting responses with few immunosuppressant effects. Denileukin diftitox (Ontak) has also been shown to produce good treatment effects, and its toxic effects can usually be controlled using prophylactic therapies. The synthetic retinoid bexarotene (Targretin) is taken orally and produces high response rates in CTCL, with a good long-term tolerability profile. Conventional systemic chemotherapies produce rapid responses and high response rates in CTCL, but these are generally of short duration and accompanied by myelosuppression and immunosuppression. Current treatment strategies therefore consist of the use of initial skin-directed therapies, with the addition of low-toxicity systemic biologic agents as the disease progresses; patients who do not respond to biologic agents should then receive conventional chemotherapies, starting with single agents and progressing to combination therapies.

Systemic Monotherapy vs Combination Therapy for CTCL: Rationale and Future Strategies

February 01, 2007

There are few approved therapies for cutaneous T-cell lymphoma (CTCL). The retinoids are the major biologic response modifiers used in CTCL, producing good response rates but few complete responses. For patients with early-stage disease, the oral retinoids can be combined with other therapies, such as psoralen plus ultraviolet A or interferon α, to improve response rates. Combined-modality therapy with oral retinoids, combined chemotherapy, electron-beam therapy, and topical mustargen has also proved effective. For the treatment of advanced-stage disease, the targeted therapy denileukin diftitox (Ontak) provides a nonimmunosuppressive alternative to conventional chemotherapy or radiation therapy. Of the conventional chemotherapies that have been tested in CTCL, gemcitabine (Gemzar) has demonstrated good efficacy in producing responses, particularly in patients with tumors. This agent can be used in combination with a maintenance therapy of bexarotene (Targretin) to manage the plaques and patches of mycosis fungoides. Several other targeted therapies are now also in testing, for example, alemtuzumab (CamPath), HuMax-CD4, several histone deacetylase inhibitors, and the transition-state inhibitor forodesine. These drugs, in combination with currently used therapies, may increase the number and combinations of therapies available for the treatment of this chronic condition to optimize long-lasting responses in CTCL.