What is Sézary syndrome (cutaneous T-cell lymphoma)?

From the Guidelines

Sézary syndrome should be treated with extracorporeal photopheresis (ECP) as the primary treatment modality, either alone or in combination with other therapies such as interferon alpha, retinoids, and total skin electron beam therapy, due to its overall response rates ranging from 30% to 80% and complete response rates ranging from 14% to 25%. This approach is based on the most recent and highest quality study available, which suggests that ECP is a effective treatment option for Sézary syndrome 1. The treatment of Sézary syndrome typically involves a multidisciplinary approach, combining systemic therapies with skin-directed therapies to manage symptoms and control the disease.

Key Considerations

• Sézary syndrome is a systemic disease, and therefore, systemic treatment is required.
• Skin-directed therapies like PUVA or potent topical steroids may be used as adjuvant therapy to manage skin symptoms.
• The standard regimen often begins with photopheresis sessions twice monthly, combined with oral bexarotene and possibly interferon alfa.
• The disease results from the proliferation of abnormal CD4+ T-cells with a memory phenotype that have lost normal immune function, leading to immune dysregulation and increased susceptibility to infections.

Treatment Options

• Extracorporeal photopheresis (ECP) is the primary treatment modality, with overall response rates ranging from 30% to 80% and complete response rates ranging from 14% to 25% 1.
• Interferon alpha, retinoids, and total skin electron beam therapy may be used in combination with ECP to enhance treatment efficacy.
• Low-dose methotrexate, bexarotene, denileukin diftitox, alemtuzumab, and multiagent chemotherapy have been recommended as second-line treatment options for Sézary syndrome 1.

Management and Monitoring

• Sézary syndrome requires ongoing management, with treatment adjusted based on response.
• Patients should be monitored closely for signs of infection, as immune dysregulation and increased susceptibility to infections are common complications of the disease.
• Vigilant monitoring and prompt treatment of infections are essential to prevent morbidity and mortality.

From the Research

Definition and Characteristics of Sezary Syndrome

• Sezary syndrome (SS) is a rare and aggressive variant of cutaneous T-cell lymphoma characterized by erythroderma, generalized lymphadenopathy, and atypical lymphocytes in peripheral blood 2.
• It is accompanied by generalized pruritus and poor quality of life 3.

Treatment Options for Sezary Syndrome

• Extracorporeal photopheresis (ECP) is recommended for the treatment of SS, and can be used as a monotherapy or in combination with other systemic agents 4, 5, 6.
• Combination therapies, such as ECP, interferon-alpha, PUVA, and topical corticosteroids, can increase response rates to ECP 4.
• Other treatment options include ultraviolet phototherapy, histone deacetylase inhibitors, novel immunotherapy agents, low-dose methotrexate, and chemotherapy 5.

Efficacy and Survival Rates of Treatment Options

• The overall response rate to ECP can range from 42% to 62%, with some patients achieving complete or partial remission 4, 6.
• The median overall survival time for SS patients can range from 31.5 months to 120 months, depending on the treatment protocol and patient population 2, 5.
• Early commencement of ECP at treatment lines 1 to 3 can result in a longer time to next treatment and improved overall survival 5.

Prognostic Variables and Markers

• Prognostic variables, such as hypereosinophilia, highly elevated β2µglobulin, male sex, and highly elevated LDH, can affect survival rates and treatment outcomes 2.
• The number of Sezary cells, CD4/CD8 ratio, and WBC count can also be used as indicators for response to treatment 4.