{"entity":{"id":"sezary-syndrome","kind":"cancer","name":"Sezary syndrome","aka":["Sézary syndrome","Sezary disease","Sézary disease","Leukaemic cutaneous T-cell lymphoma","Sezary syndrome (erythroderma with blood involvement)"],"tldr":"Sezary syndrome is the leukaemic form of skin lymphoma: the whole skin turns red and scaly, the lymph nodes swell, and malignant T cells circulate in the blood. It is treated to control rather than cure, with photopheresis, the antibody mogamulizumab, and drugs such as bexarotene and interferon, and a stem cell transplant is the only treatment that can cure it in fit patients.","summary":"WHO-HAEM5 keeps Sezary syndrome as a distinct entity from mycosis fungoides, defined by the triad of erythroderma, generalised lymphadenopathy and clonal neoplastic T cells in skin, nodes and blood, with a blood tumour burden of 1,000 or more Sezary cells per microlitre or equivalent flow cytometry criteria (Alaggio 2022; EORTC 2023). The EORTC consensus recommendations, updated in 2017 and 2023, set the stage-adapted treatment for mycosis fungoides and Sezary syndrome, noting that controlled studies remain few; the 2023 update incorporates chlormethine, brentuximab vedotin and mogamulizumab, recommends pegylated interferon after the withdrawal of unpegylated interferons, and adds guidance on supportive care and older patients (EORTC 2017; EORTC 2023). Mogamulizumab, the anti-CCR4 antibody, is the drug with a randomised trial in this setting (MAVORIC, linked here).\n\nHow it differs from its parent: the parent page covers mycosis fungoides, in which most patients have a normal life expectancy with skin-directed treatment; Sezary syndrome is advanced-stage disease by definition, blood-borne, immunosuppressing and life-shortening, treated systemically from the outset.\n\nHow common: no figure for the syndrome alone in the sources read; cutaneous T-cell lymphoma overall is about 6 per million a year (Criscione and Weinstock 2007).\n\nTreatment: extracorporeal photopheresis with or without interferon or bexarotene as first-line systemic therapy; mogamulizumab (MAVORIC) or low-dose methotrexate, pralatrexate, brentuximab vedotin in CD30-positive disease, or histone deacetylase inhibitors later; allogeneic stem cell transplant for fit patients with a response; skin-directed therapy and infection control throughout (EORTC 2023).","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/S%C3%A9zary_disease","links":[{"label":"NCI PDQ: mycosis fungoides (including Sezary syndrome) treatment","url":"https://www.cancer.gov/types/lymphoma/patient/mycosis-fungoides-treatment-pdq"},{"label":"Alaggio 2022, Leukemia: the 5th edition WHO classification of haematolymphoid tumours, lymphoid neoplasms","url":"https://doi.org/10.1038/s41375-022-01620-2"},{"label":"EORTC consensus recommendations for mycosis fungoides and Sezary syndrome, update 2023 (Eur J Cancer)","url":"https://doi.org/10.1016/j.ejca.2023.113343"},{"label":"EORTC consensus recommendations for mycosis fungoides and Sezary syndrome, update 2017 (Eur J Cancer)","url":"https://doi.org/10.1016/j.ejca.2017.02.027"},{"label":"Criscione and Weinstock 2007, Arch Dermatol: incidence of cutaneous T-cell lymphoma in the United States 1973 to 2002","url":"https://doi.org/10.1001/archderm.143.7.854"}],"tags":["subtype-page","wave4","haematologic","rare"],"related":["cutaneous-t-cell-lymphoma","peripheral-t-cell-lymphoma","t-cell-prolymphocytic-leukaemia","primary-cutaneous-marginal-zone-lymphoma","ig-tcr-clonality"],"cancers":[],"sections":[],"technologies":["allogeneic-hsct","flow-cytometry-mrd","clonality-testing"],"targets":["ccr4","cd52","stat3","stat5","jak1","jak3"],"drugs":["mogamulizumab","methoxsalen-ecp","bexarotene","interferon-alfa","methotrexate","pralatrexate","brentuximab-vedotin","romidepsin","vorinostat","resminostat","alemtuzumab","chlorambucil"],"companies":[],"institutions":[],"pathways":["jak-stat"],"terms":["allogeneic-transplant","lymphoma-tx-skin-directed-therapy","lymphoma-tx-pjp-and-infection-prophylaxis","lymphoma-bio-lineage-antigen-cost"],"trials":["mavoric","nct04930653","nct02953301"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"haematologic","burden":"A small fraction of cutaneous T-cell lymphoma, which itself had an age-adjusted incidence of 6.4 per million a year in the United States over 1973 to 2002, higher in men (8.7) than women (4.6) and in black (9.0) than white (6.1) Americans (Criscione and Weinstock 2007). No registry figure for Sezary syndrome alone is in the sources read.","subtypes":["Sezary syndrome arising de novo (the usual form)","Sezary syndrome evolving from erythrodermic mycosis fungoides","Sezary syndrome with large-cell transformation"],"biomarkers":["Sezary cell count of 1,000 per microlitre or more, or CD4:CD8 ratio of 10 or more with loss of CD7 or CD26","Clonal T-cell receptor rearrangement matching in skin and blood","CCR4 expression (mogamulizumab target)","CD30 expression (brentuximab vedotin)"],"standardOfCare":[{"setting":"First-line systemic","approach":"Extracorporeal photopheresis with or without interferon or bexarotene (EORTC 2023).","refs":["methoxsalen-ecp","bexarotene","interferon-alfa","cutaneous-t-cell-lymphoma"]},{"setting":"Later lines","approach":"Mogamulizumab (MAVORIC), methotrexate, pralatrexate, brentuximab vedotin for CD30-positive disease, romidepsin or vorinostat; allogeneic transplant for fit responders.","refs":["mogamulizumab","mavoric","methotrexate","pralatrexate","brentuximab-vedotin","romidepsin","vorinostat","allogeneic-transplant"]},{"setting":"Sezary syndrome: treatment aimed at the blood as well as the skin","approach":"Sezary syndrome is the leukaemic form: erythroderma covering most of the body, lymphadenopathy, intractable itch and a clone of malignant T cells in the blood. It is treated as advanced disease from the start, and treatment has to reduce the blood compartment, not only the skin.\n\nExtracorporeal photopheresis is the treatment most specific to it: the patient's white cells are drawn off, exposed to methoxsalen and ultraviolet A light, and returned, usually on two consecutive days every two to four weeks. It is well tolerated, works slowly over months, and is often combined with interferon alfa or bexarotene. It has been approved for the skin manifestations of cutaneous T-cell lymphoma in the United States since 1999.\n\nMogamulizumab is the systemic drug of choice where the blood is heavily involved, because in MAVORIC the response rate in the blood compartment was 68 per cent, far above its skin response; median progression-free survival was 7.7 against 3.1 months for vorinostat. Other options are bexarotene, interferon, low-dose methotrexate, romidepsin, alemtuzumab at low subcutaneous dose, chlorambucil with prednisolone for an older patient, and allogeneic transplant with reduced-intensity conditioning for fit younger patients, which is the only treatment that produces durable remission.\n\nSkin care, control of itch and prevention of staphylococcal sepsis matter at least as much as the lymphoma treatment; erythrodermic skin loses heat, fluid and protein and is an open door to infection.","refs":["methoxsalen-ecp","mogamulizumab","bexarotene","interferon-alfa","methotrexate","romidepsin","alemtuzumab","chlorambucil","prednisone","allogeneic-hsct","paper-mavoric-mogamulizumab-lancet-oncol-2018","lymphoma-tx-skin-directed-therapy","lymphoma-tx-pjp-and-infection-prophylaxis"],"guideline":{"version":"NCCN Primary Cutaneous Lymphomas; ESMO; MAVORIC","url":"https://www.cancer.gov/types/lymphoma/hp/mycosis-fungoides-treatment-pdq"}}],"stateOfArt":["Sezary syndrome is the leukaemic form, so the measurement is in blood rather than in skin: flow cytometry counts the circulating clone, and the same immunoglobulin or T-cell receptor sequence can be followed afterwards.","CCR4 is expressed in more than 80% of cases, which is why mogamulizumab is used; depleting it also removes regulatory T cells, with the rash and the transplant risk that follow.","JAK-STAT lesions recur in this family of diseases, and the STAT5B N642H substitution, which prolongs the active phosphorylated form, is the best-characterised of them."],"history":[],"pipeline":[],"openProblems":[],"parent":"cutaneous-t-cell-lymphoma"},"route":"/cancers/sezary-syndrome/","neighbours":{"cancer":[{"id":"cutaneous-t-cell-lymphoma","kind":"cancer","name":"Cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome)","route":"/cancers/cutaneous-t-cell-lymphoma/"},{"id":"lymphomatoid-papulosis","kind":"cancer","name":"Lymphomatoid papulosis","route":"/cancers/lymphomatoid-papulosis/"},{"id":"mycosis-fungoides","kind":"cancer","name":"Mycosis fungoides","route":"/cancers/mycosis-fungoides/"},{"id":"peripheral-t-cell-lymphoma","kind":"cancer","name":"Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)","route":"/cancers/peripheral-t-cell-lymphoma/"},{"id":"primary-cutaneous-anaplastic-large-cell-lymphoma","kind":"cancer","name":"Primary cutaneous anaplastic large cell lymphoma","route":"/cancers/primary-cutaneous-anaplastic-large-cell-lymphoma/"},{"id":"primary-cutaneous-marginal-zone-lymphoma","kind":"cancer","name":"Primary cutaneous marginal zone lymphoma","route":"/cancers/primary-cutaneous-marginal-zone-lymphoma/"},{"id":"t-cell-prolymphocytic-leukaemia","kind":"cancer","name":"T-cell prolymphocytic leukaemia","route":"/cancers/t-cell-prolymphocytic-leukaemia/"}],"biomarker":[{"id":"ig-tcr-clonality","kind":"biomarker","name":"Immunoglobulin and T-cell receptor clonality","route":"/biomarkers/ig-tcr-clonality/"}],"technology":[{"id":"allogeneic-hsct","kind":"technology","name":"Allogeneic stem cell transplantation","route":"/technologies/allogeneic-hsct/"},{"id":"palliative-care","kind":"technology","name":"Early integrated palliative care","route":"/technologies/palliative-care/"},{"id":"exercise-during-chemotherapy","kind":"technology","name":"Exercise during chemotherapy and radiotherapy","route":"/technologies/exercise-during-chemotherapy/"},{"id":"clonality-testing","kind":"technology","name":"Immunoglobulin and T-cell receptor clonality testing","route":"/technologies/clonality-testing/"},{"id":"multidisciplinary-tumour-board","kind":"technology","name":"Multidisciplinary tumour boards","route":"/technologies/multidisciplinary-tumour-board/"},{"id":"flow-cytometry-mrd","kind":"technology","name":"Multiparameter flow cytometry MRD","route":"/technologies/flow-cytometry-mrd/"},{"id":"fertility-preservation","kind":"technology","name":"Oncofertility and fertility preservation","route":"/technologies/fertility-preservation/"},{"id":"peer-support-groups","kind":"technology","name":"Peer support and support groups","route":"/technologies/peer-support-groups/"},{"id":"prehabilitation","kind":"technology","name":"Prehabilitation before cancer surgery","route":"/technologies/prehabilitation/"},{"id":"psycho-oncology","kind":"technology","name":"Psycho-oncology and distress screening","route":"/technologies/psycho-oncology/"},{"id":"survivorship-care-plan","kind":"technology","name":"Survivorship care and late-effects surveillance","route":"/technologies/survivorship-care-plan/"}],"target":[{"id":"ccr4","kind":"target","name":"CCR4","route":"/targets/ccr4/"},{"id":"cd52","kind":"target","name":"CD52","route":"/targets/cd52/"},{"id":"jak1","kind":"target","name":"JAK1","route":"/targets/jak1/"},{"id":"jak3","kind":"target","name":"JAK3","route":"/targets/jak3/"},{"id":"stat3","kind":"target","name":"STAT3","route":"/targets/stat3/"},{"id":"stat5","kind":"target","name":"STAT5 (STAT5A, STAT5B)","route":"/targets/stat5/"}],"drug":[{"id":"alemtuzumab","kind":"drug","name":"Alemtuzumab","route":"/drugs/alemtuzumab/"},{"id":"bexarotene","kind":"drug","name":"Bexarotene","route":"/drugs/bexarotene/"},{"id":"brentuximab-vedotin","kind":"drug","name":"Brentuximab vedotin","route":"/drugs/brentuximab-vedotin/"},{"id":"chlorambucil","kind":"drug","name":"Chlorambucil","route":"/drugs/chlorambucil/"},{"id":"interferon-alfa","kind":"drug","name":"Interferon alfa-2a/2b","route":"/drugs/interferon-alfa/"},{"id":"methotrexate","kind":"drug","name":"Methotrexate","route":"/drugs/methotrexate/"},{"id":"methoxsalen-ecp","kind":"drug","name":"Methoxsalen (extracorporeal photopheresis)","route":"/drugs/methoxsalen-ecp/"},{"id":"mogamulizumab","kind":"drug","name":"Mogamulizumab","route":"/drugs/mogamulizumab/"},{"id":"pralatrexate","kind":"drug","name":"Pralatrexate","route":"/drugs/pralatrexate/"},{"id":"prednisone","kind":"drug","name":"Prednisone","route":"/drugs/prednisone/"},{"id":"resminostat","kind":"drug","name":"Resminostat","route":"/drugs/resminostat/"},{"id":"romidepsin","kind":"drug","name":"Romidepsin","route":"/drugs/romidepsin/"},{"id":"vorinostat","kind":"drug","name":"Vorinostat","route":"/drugs/vorinostat/"}],"pathway":[{"id":"jak-stat","kind":"pathway","name":"JAK-STAT signalling","route":"/pathways/jak-stat/"}],"term":[{"id":"allogeneic-transplant","kind":"term","name":"Allogeneic stem cell transplant (allo-SCT)","route":"/terms/allogeneic-transplant/"},{"id":"cancer-related-fatigue","kind":"term","name":"Cancer-related fatigue (tiredness)","route":"/terms/cancer-related-fatigue/"},{"id":"central-venous-access","kind":"term","name":"Central venous access (port, PICC line)","route":"/terms/central-venous-access/"},{"id":"febrile-neutropenia","kind":"term","name":"Febrile neutropenia","route":"/terms/febrile-neutropenia/"},{"id":"financial-toxicity","kind":"term","name":"Financial toxicity","route":"/terms/financial-toxicity/"},{"id":"lymphoma-tx-pjp-and-infection-prophylaxis","kind":"term","name":"Infection prophylaxis in lymphoma: PJP, herpes, fungal risk and vaccination","route":"/terms/lymphoma-tx-pjp-and-infection-prophylaxis/"},{"id":"late-effects","kind":"term","name":"Late effects and survivorship toxicity","route":"/terms/late-effects/"},{"id":"neutropenia","kind":"term","name":"Neutropenia","route":"/terms/neutropenia/"},{"id":"lymphoma-tx-skin-directed-therapy","kind":"term","name":"Skin-directed therapy in mycosis fungoides: creams, light and small radiotherapy fields","route":"/terms/lymphoma-tx-skin-directed-therapy/"},{"id":"lymphoma-bio-lineage-antigen-cost","kind":"term","name":"What it costs to aim at a lineage antigen","route":"/terms/lymphoma-bio-lineage-antigen-cost/"}],"trial":[{"id":"nct04930653","kind":"trial","name":"Extracorporeal Photopheresis and Mogamulizumab for the Treatment of Erythrodermic Cutaneous T Cell Lymphoma","route":"/trials/nct04930653/"},{"id":"mavoric","kind":"trial","name":"MAVORIC","route":"/trials/mavoric/"},{"id":"nct02953301","kind":"trial","name":"Resminostat for Maintenance Treatment of Patients With Advanced Stage Mycosis Fungoides (MF) or Sézary Syndrome (SS)","route":"/trials/nct02953301/"}],"paper":[{"id":"paper-mavoric-mogamulizumab-lancet-oncol-2018","kind":"paper","name":"MAVORIC: mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma","route":"/key-papers/paper-mavoric-mogamulizumab-lancet-oncol-2018/"}]}}