Sézary syndrome

People with Sézary syndrome usually have red, itchy, peeling skin over most of the body (erythroderma). A skin doctor (dermatologist) usually takes small skin samples (skin biopsies). The changes in these samples can be subtle, so more than one biopsy, read by an experienced pathologist, is often needed.

Blood tests are central, because in Sézary syndrome the lymphoma cells are in the blood. A complete blood count (CBC) and a count of Sézary cells are done. Flow cytometry looks for T cells that have lost markers such as CD7 or CD26. A gene test (T-cell receptor gene rearrangement) checks whether many T cells come from one abnormal family, or clone. The usual rule is a T-cell clone in the blood plus at least 1,000 Sézary cells in each microliter of blood.

To see how far the lymphoma has spread (staging), the team may take a lymph node sample and order a chest x-ray, CT or PET scans. Skin and blood cancer specialists often work together on the diagnosis and the plan.

Treatment usually includes systemic therapy, often combined with skin-directed measures. Options include extracorporeal photopheresis, retinoids, interferon, mogamulizumab and other targeted agents according to the disease pattern, previous treatment and availability.

Photopheresis treats a collected portion of the patient’s white blood cells with a light-sensitive medicine and ultraviolet light before returning them. It is a treatment using the patient’s own cells, not a donor stem cell transplant.

Allogeneic transplantation may be considered for eligible patients with an appropriate disease response and risk-benefit balance. It can produce durable remission, but relapse and serious complications remain possible. Previous medicines, particularly mogamulizumab, can influence transplant planning and graft-versus-host disease risk.

When a transplant from a donor is planned, the team usually tests brothers and sisters first. Each full sibling has about a one in four chance of being a full match.

Most patients do not have a matched relative. In the words of NMDP, the U.S. registry, “75% of patients don’t have a fully matched donor in their own family.” The team then searches registries of volunteer donors around the world and banks of donated cord blood. In some transplants, a half-matched parent, child or sibling can also be the donor.

Matching depends on inherited tissue markers called HLA, so a patient is most likely to match someone who shares their ancestry. Every person who joins makes the search a little more likely to succeed, especially for patients from groups that are underrepresented on registries.

Sézary syndrome is a serious lymphoma, and standard medicines usually control it rather than cure it. Many treatments can calm the skin and lower the number of lymphoma cells in the blood, but with most treatments the benefit tends not to last long. U.S. experts describe a donor stem cell transplant as the only treatment now available that may cure it. It is an option for only some people, because it carries serious risks.

Infections are a major danger, because the immune system is weakened. The outlook depends on things such as age and stage (how far the lymphoma has spread to the blood, lymph nodes and organs). For people who have a transplant, results are better when the disease is well controlled beforehand. In U.S. registry data, survival improved modestly between 2000 and 2021.