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Sezary syndrome (SS) is a rare, leukemic variant of cutaneous lymphoma accounting for less than 5% of all types of cutaneous lymphomas. It is defined by the presence of erythroderma, lymphadenopathy, and clonal malignant T cells (>1000 abnormal cells/uL) in the blood that typically match the clone present in the skin. The malignant T cells, or Sezary cells, are analyzed by either cytopathologic assessment or, more commonly, flow cytometry and are defined as CD4+CD7− or CD4+CD26− cells. The malignant T cells appear to be derived from circulating central memory T cells that express cutaneous lymphocyte antigen (CLA), L-selectin, and high levels of the chemokine receptors CCR4 and CCR7 and are distinct from the skin-resident effector memory T cells that are the malignant T cells in mycosis fungoides.1 Treatment selection is typically based on stage of disease and is also guided by a number of additional factors including disease tempo, patient age, comorbidities, access to and cost of treatment, and prognostic factors (age >57, tumor burden, increased LDH, large cell transformation, high burden of Sezary cells in the peripheral blood > 5000/mm3, the presence of identical clones in the skin and blood, elevated blood eosinophils, presence of folliculotropism, and refractory disease). Systemic treatment is often required, but skin-directed treatment or topical therapy is often used as adjunctive treatment and patients benefit from a multidisciplinary approach at a specialty center. In addition to management of disease, it is important to address pruritus, which can be quite severe in many patients, and the prevention and treatment of infection (topical and oral antibiotics and avoidance of indwelling catheters). Response to treatment is measured monthly via clinical assessment of skin, lymph node, liver, and spleen in addition to a complete blood count, lactate dehydrogenase (LDH), complete metabolic panel, and peripheral blood flow cytometry. Time to response to treatment varies and treatment is continued if there is no evidence of disease progression and until maximal response is achieved. Treatment is then gradually tapered and continued as maintenance treatment. Clinical trials and allogeneic hematopoietic stem cell transplant are important options for refractory or high-risk disease. Clinical guidelines for diagnosis and management are frequently updated and published by the National Comprehensive Cancer Network.2 See Table 113-1.
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