Non-Hodgkin Lymphoma

See Lymphomas — Overview for the Hodgkin vs non-Hodgkin comparison table.

A heterogeneous group of cancers of B- or T-cell lymphocytes. Typically involves multiple node groups at different sites, and is generally more advanced at presentation with a worse prognosis than Hodgkin lymphoma. Classified as:

• Indolent — slowly progressive, responsive to therapy, but not typically curable with standard approaches.
• Aggressive — rapidly progressive but responsive to chemotherapy and often curable. Almost always the type seen in children.

Demographics: more common than Hodgkin lymphoma — the sixth most common cancer in the US, ~4% of all new cancer diagnoses; incidence rises with age. Cause unknown, but may be viral (EBV, HIV, hepatitis B/C, HTLV-1, HHV-8) or bacterial (H. pylori). One of the most common cancers in HIV patients.

Pattern: malaise + fever/night sweats + lymphadenopathy.

History

Painless lymphadenopathy — localised or widespread. Constitutional symptoms (sweating, fevers, weight loss) can be the first manifestation, especially in aggressive subtypes, sometimes without palpable lymphadenopathy — these patients need CT or PET imaging to find the lesion. Pruritus is possible but uncommon.

Examination

Lymphadenopathy — usually diffuse, multiple regions affected; nodes are typically rubbery, discrete, and painless, and later coalesce into larger masses (unlike the tender nodes of viral infection). Splenomegaly may be present.

Investigations

• Anaemia present in 30% at diagnosis (hypersplenism-related haemolysis or Coombs-positive haemolytic anaemia are possible mechanisms). May show peripheral lymphocytosis, as in leukaemia.
• Lymph node biopsy (core or excisional) is diagnostic — should be reviewed by a pathologist with lymphoma expertise, since correct subtype classification drives treatment choice; bone marrow biopsy may be needed for staging.
• Screen for HIV and hepatitis B/C at diagnosis (also HTLV-1 if adult T-cell leukaemia/lymphoma is suspected).

Management

Chemotherapy, radiotherapy, immunotherapy, and other options depending on staging and patient factors.

• Indolent, asymptomatic disease — “watch and wait” is a reasonable strategy; stage I disease can sometimes be cured with radiotherapy alone.
• Aggressive B-cell NHL (e.g. DLBCL) — R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) is standard; complete response in 70–80% of cases, overall cure rate ~60–70%.
• Relapsed/refractory aggressive B-cell NHL — autologous stem cell transplant, or CAR-T cell therapy (e.g. axicabtagene ciloleucel, tisagenlecleucel) once patients have failed ≥2 prior lines or progressed within 12 months of frontline therapy; roughly 60% of second-line and 30% of later-line CAR-T recipients achieve a durable response.

Treatment complications: neutropenia and subsequent infection. Later complications: in the first 10 years, myelodysplasia or acute leukaemia from chemotherapy-related bone marrow damage; after 10 years, risk of secondary cancers rises, especially with chest radiotherapy.