# Hepatosplenic T-cell lymphoma

Source: https://onco.cc/cancers/hepatosplenic-t-cell-lymphoma/  
OnCo record `hepatosplenic-t-cell-lymphoma` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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).

How 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.

How common: no registry share in the sources read; rare.

Treatment: 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).

## Fields

- Kind: Cancer
- Last checked: 2026-09-24
- Also known as: HSTCL; HSTL; Hepatosplenic gamma-delta T-cell lymphoma; Enteropathy-associated and hepatosplenic T-cell lymphoma
- Tags: subtype-page; wave4; haematologic; rare
- 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

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/hepatosplenic-t-cell-lymphoma/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/hepatosplenic-t-cell-lymphoma/#overview
- What it is (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/hepatosplenic-t-cell-lymphoma/#what-it-is [3 subtypes]
- Finding it (on the hub): How it shows itself, how it is confirmed, what screening exists, and the biomarkers clinicians test for. https://onco.cc/cancers/hepatosplenic-t-cell-lymphoma/#finding-it [4 biomarkers]
- Treating it (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/hepatosplenic-t-cell-lymphoma/#treating-it [1 setting, 1 decision with options]
- Evidence (on the hub): Trials recruiting now, the landmark trials, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/hepatosplenic-t-cell-lymphoma/#evidence
- The science (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/hepatosplenic-t-cell-lymphoma/#science [2 targets, 1 pathway]
- Where you are (own page): Cases by country, the UK and NHS pathway and other country lenses, and the expert centres with trials on record. https://onco.cc/cancers/hepatosplenic-t-cell-lymphoma/where-you-are/
- Living with it (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/hepatosplenic-t-cell-lymphoma/#living-with-it [8 questions, 3 red cards]
- What is coming (own page): Everything in development, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/hepatosplenic-t-cell-lymphoma/coming/ [3 medicines]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/hepatosplenic-t-cell-lymphoma/data/ [12 connected records]

## Standard of care

- All cases: Intensive platinum- and cytarabine-based induction rather than CHOP, then allogeneic or autologous transplant in first remission for fit patients. ([Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)](https://onco.cc/cancers/peripheral-t-cell-lymphoma/), [Cytarabine](https://onco.cc/drugs/cytarabine/), [Cisplatin](https://onco.cc/drugs/cisplatin/), [Allogeneic stem cell transplant (allo-SCT)](https://onco.cc/terms/allogeneic-transplant/))

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Hepatosplenic_T-cell_lymphoma
- NCI PDQ: adult non-Hodgkin lymphoma treatment: https://www.cancer.gov/types/lymphoma/patient/adult-nhl-treatment-pdq
- Alaggio 2022, Leukemia: the 5th edition WHO classification of haematolymphoid tumours, lymphoid neoplasms: https://doi.org/10.1038/s41375-022-01620-2
- McKinney 2017, Cancer Discovery: the genetic basis of hepatosplenic T-cell lymphoma, 68 cases: https://doi.org/10.1158/2159-8290.cd-16-0330
- Clin Gastroenterol Hepatol 2011: factors contributing to hepatosplenic T-cell lymphoma in inflammatory bowel disease: https://doi.org/10.1016/j.cgh.2010.09.016

## Connected records

- cancers: [Nodal T-follicular helper cell lymphoma, angioimmunoblastic type (angioimmunoblastic T-cell lymphoma)](https://onco.cc/cancers/angioimmunoblastic-t-cell-lymphoma/), [Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)](https://onco.cc/cancers/peripheral-t-cell-lymphoma/), [Post-transplant lymphoproliferative disorder (PTLD)](https://onco.cc/cancers/post-transplant-lymphoproliferative-disorder/), [T-cell large granular lymphocytic leukaemia](https://onco.cc/cancers/t-large-granular-lymphocytic-leukaemia/)
- targets: [STAT3](https://onco.cc/targets/stat3/)
- drugs: [Cisplatin](https://onco.cc/drugs/cisplatin/), [Cytarabine](https://onco.cc/drugs/cytarabine/), [Etoposide](https://onco.cc/drugs/etoposide/)
- pathways: [JAK-STAT signalling](https://onco.cc/pathways/jak-stat/)
- terms: [Allogeneic stem cell transplant (allo-SCT)](https://onco.cc/terms/allogeneic-transplant/)

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JSON: https://onco.cc/api/v1/entities/hepatosplenic-t-cell-lymphoma.json