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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
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.
| Setting | Approach | Guideline |
|---|---|---|
| Aggressive B-cell (DLBCL and related) | Curative immunochemotherapy (R-CHOP or Pola-R-CHP); CAR-T or bispecific antibodies at relapse. See the DLBCL page. | not mapped |
| Indolent B-cell (follicular, marginal zone) | 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. | not mapped |
| Mantle cell lymphoma and CLL | BTK inhibitors and venetoclax-based regimens have largely replaced chemotherapy. See the mantle cell and CLL pages. | not mapped |
| T-cell lymphomas | CHOP-based chemotherapy, brentuximab vedotin for CD30-positive disease, transplant in first remission for fit patients. See the peripheral T-cell lymphoma page. | not mapped |
| How the treatment of a non-Hodgkin lymphoma is decided | 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. | not mapped |
| Supportive care that belongs to lymphoma specifically | 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. | not mapped |
| Where British and American practice differ | 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. | not mapped |
| Treatments that did not work, and are worth not being offered | 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. | not mapped |