13.          Non-Hodgkin’s Lymphoma, extranodal primaries

13.2        Primary cutaneous lymphomas

13.2.1 B- cell lymphoma

Primary cutaneous B-cell lymphoma (CBCL) is generally an indolent disease with a good prognosis. Although local cutaneous recurrences are often observed, dissemination outside the skin usually occurs late in the course of the disease.

The majority of cases is highly responsive to radiotherapy. Polychemotherapy (e.g. COP/CHOP) should, therefore, be reseved for involvement of non- contiguous anatomic sites or those with extracutaneous spread.

Literature: for review

            PANDOLFINO et al, J. Clin. Oncol. 18 (2000): 2152-2168

13.2.2 T-cell lymphoma

13.2.2.1                  General considerations

Cutaneous T-cell lymphomas (CTCL) comprise a number of clonal T-cell malignancies with primary manifestation in the skin.

The most common “ classical” subset of these diseases includes mycosis fungoides and Sezary’s syndrome, its aggressive variant that is characterized by erythroderma and leukemia.

Therapeutic options should primarily be determined by the clinical stage and extent of disease involvement. Patients with early patch/plaque mycosis fungoides are candidates for skin-directed therapies such as phototherapy with psoralen+ ultraviolet A (PUVA) with or without interferon alpha, topical chemotherapy (nitrogen mustard), ionizing radiation or systemic biological response modifiers including retinoids. Patients with IIB disease usually require more intensive therapy, like total skin electron beam radiation, retinoids (e.g. bexarotene) or the recombinant fusion toxin denileukin diftitox. Systemic chemotherapy may be required in patients with disease refractory to skin-directed treatment. Patients with stage III disease or Sezary’s syndrome who have leukemic involvement are often best treated with extracorporeal photopheresis as monotherapy or in combination with interferon, retinoids or radiation. Patients with advanced extracutaneous disease require more aggressive therapies such as systemic chemotherapy and/or investigational approaches (e.g. the anti-CD52 monoclonal antibody alemtuzumab). Allogeneic hematopoietic stem cell transplantation may have the potential for sustained remission and the possibility of cure for selected young patients with advanced or biologically aggressive CTCL.

            Literature: for review

                        APISARNTHANARAX et al, Am. J. Clin. Dermatol. 3 (2002): 193-215

GUITART et al, Arch. Dermatol. 138 (2002): 1359-1365 (allogeneic hematopoietic stem cell transplantation)

                        STADLER, Skin Pharmacol. Appl. Skin Physiol. 15(2002): 139 – 146

                        VONDERHEID, Recent Results Cancer Res. 160 (2002): 309 – 320

13.2.2.2                  Bexarotene

The capsules are taken as a once-daily dose with meals. The time to response is generally within 2 months. A topically applicable gel formulation is also available.

            Literature:

BRENEMAN et al, Arch, Dermatol. 138 (2002): 325-332 (phase I and II trial of  bexarotene gel)

DUVIC et al, J. Clin. Oncol. 19 (2001): 2456-2471 (multinational phase II and III trial results)

TALPUR et al, J. Am. Acad. Dermatol. 47 (2002): 672-684 (oral bexarotene as monotherapy and in combination with other active agents)

13.2.2.3                  Denileukin diftitox (DAB- IL2)

            Every 3 weeks (max 8 cycles or 6 months of therapy) with corticosteroid premedication.

For the treatment of patients with persistent or recurrent cutaneous T-cell lymphoma whose malignant cells express the CD25 component of the IL-2 receptor.

            Literature:

                        DUVIC et al, Clin. Lymphoma 2 (2002): 222-228 (quality of life aspects)

                        OLSEN et al, J. Clin. Oncol. 19 (2001): 376- 388 (phase III pivotal trial)