{"entity":{"id":"hepatosplenic-t-cell-lymphoma","kind":"cancer","name":"Hepatosplenic T-cell lymphoma","aka":["HSTCL","HSTL","Hepatosplenic gamma-delta T-cell lymphoma","Enteropathy-associated and hepatosplenic T-cell lymphoma"],"tldr":"Hepatosplenic T-cell lymphoma is a rare, very aggressive lymphoma of young men in which gamma-delta T cells fill the liver, spleen and bone marrow without forming lumps in the nodes. It is linked to long-term immune suppression, above all thiopurines with or without anti-TNF drugs for inflammatory bowel disease, and is treated with intensive chemotherapy then a stem cell transplant where possible.","summary":"WHO-HAEM5 keeps hepatosplenic T-cell lymphoma as an entity of cytotoxic, usually gamma-delta T cells with sinusoidal infiltration of spleen, liver and marrow, isochromosome 7q and an aggressive course (Alaggio 2022). Whole-exome sequencing of 68 cases defined its drivers: chromatin-modifying genes (SETD2, INO80, ARID1B) mutated in 62 percent, SETD2 the most frequently silenced and shown to act as a tumour suppressor, and STAT5B (31 percent), STAT3 (9 percent) and PIK3CD (9 percent) mutations that activate targetable signalling (McKinney 2017). Of 36 patients with the lymphoma arising during treatment of inflammatory bowel disease, 20 had received infliximab with a thiopurine and 16 a thiopurine alone; 27 of 30 with known age were under 35 and only 2 of 31 were women (Clin Gastroenterol Hepatol 2011).\n\nHow it differs from its parent: no lymphadenopathy, a leukaemic and hepatosplenic pattern, a young male population, an iatrogenic immunosuppression association, and an outcome worse than most peripheral T-cell lymphomas, with median survival under two years in the older literature and CHOP alone rarely producing durable remission.\n\nHow common: no registry share in the sources read; rare.\n\nTreatment: intensive induction (ICE, IVAC or similar platinum- and cytarabine-containing regimens rather than CHOP) followed by allogeneic or autologous stem cell transplant in first remission for fit patients, as on the parent page; JAK-STAT and PI3K-delta inhibitors are the rational targets from the genetics but have no trial (McKinney 2017).","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Hepatosplenic_T-cell_lymphoma","links":[{"label":"NCI PDQ: adult non-Hodgkin lymphoma treatment","url":"https://www.cancer.gov/types/lymphoma/patient/adult-nhl-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":"McKinney 2017, Cancer Discovery: the genetic basis of hepatosplenic T-cell lymphoma, 68 cases","url":"https://doi.org/10.1158/2159-8290.cd-16-0330"},{"label":"Clin Gastroenterol Hepatol 2011: factors contributing to hepatosplenic T-cell lymphoma in inflammatory bowel disease","url":"https://doi.org/10.1016/j.cgh.2010.09.016"}],"tags":["subtype-page","wave4","haematologic","rare"],"related":["peripheral-t-cell-lymphoma","angioimmunoblastic-t-cell-lymphoma","t-large-granular-lymphocytic-leukaemia","post-transplant-lymphoproliferative-disorder"],"cancers":[],"sections":[],"technologies":[],"targets":["stat3"],"drugs":["cytarabine","cisplatin","etoposide"],"companies":[],"institutions":[],"pathways":["jak-stat"],"terms":["allogeneic-transplant"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"haematologic","burden":"Rare and usually fatal, affecting mainly men under 35 (Clin Gastroenterol Hepatol 2011); the largest genetic study holds 68 cases (McKinney 2017). No registry share is in the sources read.","subtypes":["Hepatosplenic T-cell lymphoma, gamma-delta type (the usual form)","Hepatosplenic T-cell lymphoma, alpha-beta type","Hepatosplenic T-cell lymphoma after thiopurine or anti-TNF therapy (inflammatory bowel disease, transplant)"],"biomarkers":["Sinusoidal infiltration of spleen, liver and marrow; gamma-delta T-cell receptor","Isochromosome 7q and trisomy 8","SETD2, STAT5B, STAT3 and PIK3CD mutations","History of thiopurine or anti-TNF exposure"],"standardOfCare":[{"setting":"All cases","approach":"Intensive platinum- and cytarabine-based induction rather than CHOP, then allogeneic or autologous transplant in first remission for fit patients.","refs":["peripheral-t-cell-lymphoma","cytarabine","cisplatin","allogeneic-transplant"]}],"stateOfArt":[],"history":[],"pipeline":[],"openProblems":[],"parent":"peripheral-t-cell-lymphoma"},"route":"/cancers/hepatosplenic-t-cell-lymphoma/","neighbours":{"cancer":[{"id":"angioimmunoblastic-t-cell-lymphoma","kind":"cancer","name":"Nodal T-follicular helper cell lymphoma, angioimmunoblastic type (angioimmunoblastic T-cell lymphoma)","route":"/cancers/angioimmunoblastic-t-cell-lymphoma/"},{"id":"peripheral-t-cell-lymphoma","kind":"cancer","name":"Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)","route":"/cancers/peripheral-t-cell-lymphoma/"},{"id":"post-transplant-lymphoproliferative-disorder","kind":"cancer","name":"Post-transplant lymphoproliferative disorder (PTLD)","route":"/cancers/post-transplant-lymphoproliferative-disorder/"},{"id":"t-large-granular-lymphocytic-leukaemia","kind":"cancer","name":"T-cell large granular lymphocytic leukaemia","route":"/cancers/t-large-granular-lymphocytic-leukaemia/"}],"target":[{"id":"stat3","kind":"target","name":"STAT3","route":"/targets/stat3/"}],"drug":[{"id":"cisplatin","kind":"drug","name":"Cisplatin","route":"/drugs/cisplatin/"},{"id":"cytarabine","kind":"drug","name":"Cytarabine","route":"/drugs/cytarabine/"},{"id":"etoposide","kind":"drug","name":"Etoposide","route":"/drugs/etoposide/"}],"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/"}]}}