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Non-Hodgkin lymphoma is not one disease but a family of more than sixty cancers of the lymphocytes, the white blood cells of the immune system. About 95 per cent come from B cells and the rest from T or NK cells; some grow over years and are watched, others grow over weeks and are treated to cure. The family is the map; the subtype is the disease, and the subtype is what decides the treatment.
What it is. Non-Hodgkin lymphoma is not a disease. It is the name given to every cancer of the lymphatic system that is not Hodgkin lymphoma, and it covers scores of separate diseases whose only shared feature is the cell they come from: the tables of the 2022 WHO classification list more than sixty mature B-cell, T-cell and NK-cell entities: a lymphocyte, one of the white blood cells that run the immune system. Two people both told they have non-Hodgkin lymphoma may have conditions that differ more from each other than breast cancer differs from bowel cancer. One may be watched for ten years without treatment; the other may start chemotherapy the week of diagnosis with the intention of cure. The single most useful thing to find out after the word lymphoma is the rest of the name on the report, because that is what decides everything.
How the classification is built, in plain words. The reference book is the fifth edition of the World Health Organization Classification of Haematolymphoid Tumours, published in 2022 and usually shortened to WHO-HAEM5. It does not use the phrase non-Hodgkin lymphoma at all. It sorts lymphomas on a tree: first by the class of cell, then into a family of related diseases, then into the entity that is the diagnosis. The first fork is B-cell on one side and T-cell and NK-cell on the other. B cells make antibodies; T cells and NK cells kill infected cells directly. In the United Kingdom the B-cell side is about 95 per cent of lymphoma diagnoses and the T-cell and NK-cell side about 5 per cent (Haematological Malignancy Research Network, 5,796 lymphomas in a population of nearly four million). That first fork matters because B cells carry a protein called CD20 on their surface and T cells do not, and the antibody that attaches to CD20, rituximab, is the drug that transformed B-cell lymphoma from 1997 onwards and has no equivalent on the T-cell side.
The second thing a reader is told is the pace, and it is the fork that decides what happens next week. Indolent lymphomas grow over years: follicular lymphoma, marginal zone lymphoma, lymphoplasmacytic lymphoma, most cutaneous T-cell lymphoma. They are generally not curable with the treatments in use today, and they are also not usually urgent, so a person with no symptoms may reasonably be watched rather than treated, sometimes for a decade. Aggressive lymphomas grow over weeks: diffuse large B-cell lymphoma, high-grade B-cell lymphoma, Burkitt lymphoma, most of the T-cell lymphomas. They are treated immediately and they are treated to cure. The sentence that surprises people most is that the aggressive ones are the ones more often cured, and the slow ones the ones more often lived with. Waiting is not neglect in an indolent lymphoma; it is the treatment that has been shown not to shorten life, and the glossary entry on watching and waiting says what is being watched for.
The third fork is where the lymphoma is. Nodal lymphoma arises in lymph nodes, the bean-sized filters strung along the lymphatic vessels, and shows itself as a painless lump in the neck, armpit or groin. Extranodal lymphoma arises in an organ that has lymphoid tissue in it but is not a lymph node: the stomach, the eye socket, the skin, the brain, the testis, the small bowel, the thyroid, the salivary gland. A substantial minority of non-Hodgkin lymphomas start outside the lymph nodes, and the site changes the disease. A marginal zone lymphoma in the stomach is usually caused by a bacterial infection and is usually cured by a fortnight of antibiotics; the same cell type in a lymph node is not. A large B-cell lymphoma in the testis, the eye or the brain behaves as one disease across those three sites, which WHO-HAEM5 recognised in 2022 by grouping them as lymphomas of immune-privileged sites, places the immune system does not patrol.
Who gets it. Lymphoma is mostly a disease of later life: the median age at diagnosis in the HMRN population was 67.2 years for all lymphomas together and 69.1 years for the non-Hodgkin group, with men diagnosed younger than women and at higher rates at almost every age. But the family spans every age, and different subtypes dominate different ages: Burkitt lymphoma and Hodgkin lymphoma are the common lymphomas of childhood and early adult life, while above 60 the diffuse large B-cell, marginal zone and follicular subtypes account for more than 80 per cent of diagnoses. Most people with lymphoma have no identifiable cause. The known causes account for a minority and are worth naming because several are preventable or treatable: Epstein-Barr virus, the virus of glandular fever, which is involved in Burkitt lymphoma, in some diffuse large B-cell lymphomas and in extranodal NK/T-cell lymphoma; Helicobacter pylori in the stomach; hepatitis C; HIV; HTLV-1, which causes adult T-cell leukaemia/lymphoma; Kaposi sarcoma herpesvirus, which causes primary effusion lymphoma; coeliac disease, which precedes enteropathy-associated T-cell lymphoma; immune suppression after an organ transplant; and autoimmune diseases such as Sjogren syndrome and Hashimoto thyroiditis, which produce the lymphoid tissue that marginal zone lymphomas grow in. Cancer Research UK estimates that about 3 per cent of UK cases are preventable, which is the honest counterpart to the fact that most people did nothing to cause this.
How it is staged, and why the old words survive. Lymphoma is not staged with the TNM system used for solid tumours, because it does not have a primary tumour and lymph nodes in the way a breast or bowel cancer does: in lymphoma, the lymph nodes are the disease. The system in use is the Lugano classification, agreed at the International Conference on Malignant Lymphoma in Lugano in 2011 and published in 2014. It counts how many regions of lymph nodes are involved and whether they sit on one side of the diaphragm or both: stage I is one region, stage II is two or more on the same side, stage III is both sides, stage IV is disease that has spread diffusely into an organ such as the bone marrow, liver or lung. Lugano kept the descriptive language of the Ann Arbor system that preceded it, agreed at a meeting in Ann Arbor, Michigan in 1971 for Hodgkin's disease, which is why a report in 2026 may still say Ann Arbor stage IIA and mean the same thing. What Lugano changed is how the stage is measured: PET-CT scanning became the standard staging test for the lymphomas that take up the tracer, the A and B suffixes for fever, night sweats and weight loss are now recorded only for Hodgkin lymphoma, and a routine bone marrow biopsy is no longer needed to stage Hodgkin lymphoma or, in most cases, diffuse large B-cell lymphoma.
Stage is not the main thing. This is the largest difference between lymphoma and the cancers most people have heard of. In breast or bowel cancer the stage is the dominant fact; in lymphoma the subtype matters more, and within a subtype the prognosis is read from a score that counts clinical features rather than anatomy. The International Prognostic Index, built in 1993 from 2,031 patients with aggressive lymphoma treated across 16 institutions, counts five: age over 60, stage III or IV, a raised lactate dehydrogenase, a performance status of 2 or worse, and more than one site outside the lymph nodes. Follicular lymphoma has its own version (FLIPI), mantle cell lymphoma has MIPI, and the nodal T-cell lymphomas have the Prognostic Index for T-cell lymphoma, built from 385 patients in 2004. Stage IV lymphoma is a routine curable diagnosis, which is the opposite of what the word means in most other cancers, and it is worth saying out loud at the point where somebody has just been handed the number.
The state of the art, in one paragraph. The B-cell side has had thirty years of advances that compound. Rituximab, approved in 1997, was the first antibody ever licensed for a cancer, and adding it to chemotherapy raised both the proportion of people whose diffuse large B-cell lymphoma went away and the proportion still alive years later; the trial and its figures are on that page. CAR-T cell therapy, in which a patient's own T cells are collected, engineered to recognise CD19 and given back, was approved for relapsed large B-cell lymphoma in 2017 and now cures a proportion of people whose disease had come back after chemotherapy. Bispecific antibodies, which grip a lymphoma cell with one arm and a T cell with the other, arrived in 2023 and do a related job without the manufacturing wait. Antibody-drug conjugates deliver chemotherapy to the cell that carries a particular marker. The T-cell and NK-cell side has had almost none of this: there is no CD20 to aim at, the entities are individually rare, and brentuximab vedotin added to chemotherapy for CD30-positive disease is the only randomised first-line advance in twenty years. The gap between the two sides of the first fork is the largest unsolved problem in this family, and it is a gap in research effort as much as in biology.
A note on names. Because two classifications were published in 2022 and they do not agree about everything, a British report, an American report and a trial protocol may give the same disease three names. Where that happens the pages in this family give both and say which book each name comes from. The glossary entry on the two classifications lists the disagreements that change what a patient is called.
It is the commonest group of blood cancers.
Averages across everyone diagnosed, often years ago. A median is the middle of a group: half the people counted lived longer than the figure shown, and some lived far longer. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
Leukaemias, myeloma and MDS live in the marrow and blood; lymphomas grow in lymph nodes and spleen. The node stations are the disease map, not a route of spread, and staging counts them.
In lymphoma the node stations are the disease itself; staging (Ann Arbor / Lugano) counts how many regions and sides of the diaphragm are involved.
Same organ: High-grade B-cell lymphoma with MYC and BCL2 rearrangements (double-hit lymphoma), Mediastinal grey zone lymphoma, Primary effusion lymphoma, Plasmablastic lymphoma, T-cell/histiocyte-rich large B-cell lymphoma, EBV-positive diffuse large B-cell lymphoma, Primary large B-cell lymphoma of the testis, Gastric MALT lymphoma, Ocular adnexal MALT lymphoma, Extranodal NK/T-cell lymphoma, Adult T-cell leukaemia/lymphoma, ALK-positive anaplastic large cell lymphoma, ALK-negative anaplastic large cell lymphoma, Breast implant-associated anaplastic large cell lymphoma, Primary cutaneous anaplastic large cell lymphoma, Lymphomatoid papulosis, Mycosis fungoides, Enteropathy-associated T-cell lymphoma, Monomorphic epitheliotropic intestinal T-cell lymphoma, Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), Splenic marginal zone lymphoma, Nodal marginal zone lymphoma, Primary cutaneous marginal zone lymphoma, Primary cutaneous follicle centre lymphoma, Sezary syndrome, Nodal T-follicular helper cell lymphoma, angioimmunoblastic type (angioimmunoblastic T-cell lymphoma), Hepatosplenic T-cell lymphoma, Intravascular large B-cell lymphoma, Lymphomatoid granulomatosis, T-cell prolymphocytic leukaemia, Splenic B-cell lymphoma/leukaemia with prominent nucleoli (formerly B-cell prolymphocytic leukaemia and hairy cell leukaemia variant), T-cell large granular lymphocytic leukaemia, Mixed-phenotype acute leukaemia, Myeloid leukaemia of Down syndrome, Burkitt leukaemia, Marginal zone lymphoma, Cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome), Primary mediastinal (thymic) large B-cell lymphoma, Leukaemia (all types), Acute myeloid leukaemia, Acute lymphoblastic leukaemia, Chronic lymphocytic leukaemia, Chronic myeloid leukaemia (CML), Diffuse large B-cell lymphoma, Follicular lymphoma, Hodgkin lymphoma, Mantle cell lymphoma, Multiple myeloma, Myelodysplastic syndromes / neoplasms (MDS), Myeloproliferative neoplasms (PV, ET, myelofibrosis), Polycythaemia vera (PV), Essential thrombocythaemia (ET), Waldenström macroglobulinaemia, Hairy cell leukaemia, Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma), Blastic plasmacytoid dendritic cell neoplasm (BPDCN), Burkitt lymphoma, HIV-associated (AIDS-related) lymphomas, Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms, Systemic mastocytosis, Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms, Langerhans cell histiocytosis (LCH), Post-transplant lymphoproliferative disorder (PTLD), FLT3-mutated acute myeloid leukaemia, IDH1- and IDH2-mutated acute myeloid leukaemia, NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia, Secondary and therapy-related acute myeloid leukaemia, Acute promyelocytic leukaemia, Acute myeloid leukaemia in older or unfit patients, Smouldering multiple myeloma, Newly diagnosed multiple myeloma, transplant-eligible, Newly diagnosed multiple myeloma, transplant-ineligible, Relapsed or refractory multiple myeloma, Plasma cell leukaemia, Lower-risk myelodysplastic syndromes, Higher-risk myelodysplastic syndromes, Chronic lymphocytic leukaemia, first treatment, Relapsed or refractory chronic lymphocytic leukaemia, Richter transformation of chronic lymphocytic leukaemia, Chronic myeloid leukaemia, chronic phase, Chronic myeloid leukaemia, accelerated and blast phase, Primary myelofibrosis, Standard-risk B-cell acute lymphoblastic leukaemia in children, High-risk acute lymphoblastic leukaemia in children (high-risk B-ALL and T-ALL), Philadelphia chromosome-positive acute lymphoblastic leukaemia in children (Ph-positive ALL), Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like or BCR::ABL1-like ALL), Infant acute lymphoblastic leukaemia (KMT2A-rearranged, under one year), Relapsed and refractory acute lymphoblastic leukaemia in children, Acute myeloid leukaemia in children, Erdheim-Chester disease, Rosai-Dorfman-Destombes disease, Single-system Langerhans cell histiocytosis (bone, skin or one other organ), Multisystem Langerhans cell histiocytosis (with or without risk-organ involvement), Indolent and smouldering systemic mastocytosis, Advanced systemic mastocytosis (aggressive SM, SM with an associated haematological neoplasm, mast cell leukaemia), Early-stage classical Hodgkin lymphoma (stage I to II), Advanced-stage classical Hodgkin lymphoma (stage III to IV), Nodular lymphocyte-predominant Hodgkin lymphoma (nodular lymphocyte-predominant B-cell lymphoma), Relapsed and refractory classical Hodgkin lymphoma
Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads.
Nothing recorded yet.
Also on OnCo: Symptoms and red flags · Early detection roadmap.
Curative immunochemotherapy (R-CHOP or Pola-R-CHP); CAR-T or bispecific antibodies at relapse. See the DLBCL page.
Watch and wait when asymptomatic; rituximab alone or with bendamustine or CHOP when treatment is needed; bispecifics and CAR-T for later relapses. See the follicular lymphoma page.
BTK inhibitors and venetoclax-based regimens have largely replaced chemotherapy. See the mantle cell and CLL pages.
CHOP-based chemotherapy, brentuximab vedotin for CD30-positive disease, transplant in first remission for fit patients. See the peripheral T-cell lymphoma page.
Three questions, in order. Is it aggressive or indolent? Aggressive lymphomas (diffuse large B-cell, high-grade B-cell, Burkitt, most T-cell lymphomas, blastoid mantle cell) are treated immediately, with combination chemotherapy, with the intention to cure. Indolent lymphomas (follicular, marginal zone, lymphoplasmacytic) may not need treatment at all for years, and when they do the aim is control rather than cure. Is it a B-cell or a T-cell lymphoma? B-cell lymphomas carry CD20 and almost all first-line regimens contain an anti-CD20 antibody; T-cell lymphomas do not, which is the main reason their outcomes lag. Where is it, and what does it threaten? A lymphoma in the stomach, the brain, the testis, the eye or the skin is treated by rules specific to that site, not by the rules for nodal disease. The things that must be done before the first dose are the same across the family: a proper biopsy reported to the current WHO classification, PET-CT staging reported by the Lugano classification, hepatitis B and HIV testing, and a fertility conversation.
Five things, each with its own entry. Tumour lysis syndrome: predictable from bulk, LDH and histology, prevented with fluids, allopurinol and, in high-risk patients, rasburicase; screen for glucose-6-phosphate dehydrogenase deficiency first. Hepatitis B reactivation: test surface antigen and core antibody before any anti-CD20 antibody and give entecavir or tenofovir prophylaxis, which in a randomised trial cut reactivation from 30 to 6.6 per cent against lamivudine. Pneumocystis and herpes prophylaxis with steroid-containing, purine-analogue, PI3K-inhibitor, CAR-T and bispecific regimens. Immunoglobulin replacement for those left with low IgG and recurrent infection after B-cell depletion. Cytokine release syndrome and ICANS after CAR-T and bispecific antibodies, graded by the ASTCT criteria and treated with tocilizumab and steroids. Fertility preservation before alkylating chemotherapy, arranged in days rather than weeks.
In advanced Hodgkin lymphoma, the United States moved to nivolumab with AVD after SWOG S1826 while Germany moved to PET-guided BrECADD after HD21 and British practice sits between the two. In older mantle cell lymphoma, the British-led ENRICH trial made ibrutinib with rituximab a first-line option without chemotherapy, with the benefit concentrated against R-CHOP rather than against bendamustine-rituximab. In first-line diffuse large B-cell lymphoma, pola-R-CHP is the American default for IPI 2 and above while R-CHOP remains the commonest first treatment in England. Central nervous system prophylaxis has been dropped faster in the United Kingdom than in the United States. Access to bispecific antibodies and CAR-T exists in both countries by different routes: national commissioning and panel approval in England, insurance authorisation at an accredited centre in the United States.
DA-EPOCH-R as a general upgrade to R-CHOP failed in Alliance/CALGB 50303. Obinutuzumab in place of rituximab in diffuse large B-cell lymphoma failed in GOYA, although it works in follicular lymphoma in GALLIUM. Lenalidomide maintenance after R-CHOP lengthened progression-free survival but not life in REMARC. Tisagenlecleucel in second line failed in BELINDA while two other CAR-T products succeeded in the same setting. Four gray in two fractions is inferior to 24 gray for curative radiotherapy of indolent lymphoma in FoRT. Central nervous system prophylaxis did not lower central nervous system relapse below the rate predicted by CNS-IPI in the largest cohort that received it.
Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year.
Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Lymphoma Action says a small number of people have more serious problems such as seizures or swelling of the brain, treated with steroids and intensive care, and that most improve within a few days of treatment starting. This is 999.
Breathing very fast, confusion or slurred speech, blue, pale or blotchy skin, a very high or very low temperature, shivering, or a rash that does not fade when pressed: the NHS says call 999 or go to A and E, and do not drive yourself.
A rising potassium level can disturb the heart rhythm, which is the reason blood is checked frequently during the first cycle. The triage standard sends chest pain or tightness straight to 999 whatever the cause.
Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
Any new neurological symptom that is not explained. Brentuximab vedotin carries a boxed warning for progressive multifocal leukoencephalopathy, a brain infection; the label says to hold the drug and investigate at the first suspicion.
Blood in stool or urine, vomiting blood, a bleed that will not stop, or a severe headache; fatal bleeding events have occurred and the labels advise considering the risk around surgery and with blood thinners.
See all on the product pages:BendamustineBrentuximab vedotinCD20 bispecific antibodies: step-up dosing, fixed duration and what it is like to take oneCentral venous access (port, PICC line)Cytokine release syndrome (CRS)Cytokine release syndrome and ICANS: grading and managementFebrile neutropeniaHypogammaglobulinaemia and infection risk after B-cell therapiesIbrutinibICANS (neurotoxicity)NeutropeniaThe CAR-T pathway in lymphoma: referral, apheresis, bridging and the waitingTumour lysis syndrome (TLS)Tumour lysis syndrome in lymphoma: who is at risk, and rasburicase·Printable cards in the navigator
Newly diagnosed? Read the first 60 days with Non-Hodgkin lymphoma, then print the one-page appointment sheet with room for the answers.
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Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record.
Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked.