Non-Hodgkin Lymphoma (NHL)

Non-Hodgkin lymphoma (NHL) is a group of cancers that start in lymphocytes — white blood cells of the immune system found in lymph nodes, spleen, bone marrow and other organs.

There are more than 60 subtypes, from slow-growing (indolent) lymphomas that may need no immediate treatment, to aggressive lymphomas that need prompt therapy but are often curable. An exact diagnosis is therefore the foundation of good care.

What causes non-Hodgkin lymphoma?

Most people have no clear cause. Risk factors include:

• A weakened immune system (HIV, organ transplant medicines, some autoimmune diseases)
• Infections such as Epstein–Barr virus, Helicobacter pylori, hepatitis C and HTLV-1
• Older age
• Exposure to certain pesticides and chemicals
• Previous chemotherapy or radiation therapy

Symptoms

• Painless swelling of lymph nodes in the neck, armpit or groin
• Fever, drenching night sweats and unexplained weight loss
• Tiredness, itching
• Cough or breathlessness (lymphoma in the chest); abdominal pain or swelling

Common types

• Diffuse large B-cell lymphoma (DLBCL) — the most common aggressive lymphoma
• Follicular lymphoma — the most common slow-growing lymphoma
• Mantle cell, marginal zone and Burkitt lymphoma
• T-cell lymphomas, such as peripheral T-cell and anaplastic large cell lymphoma

Diagnosing NHL needs a tissue sample and a full staging work-up to show the exact subtype and where the disease is in the body.

Complete blood count (CBC)

Together with LDH, kidney and liver tests and screening for hepatitis B, C and HIV before treatment.

Biopsy

An excisional or core-needle biopsy of an enlarged lymph node (or another affected organ) is examined by an experienced hematopathologist. A whole node gives the most information.

Flow cytometry and immunohistochemistry

Markers on the lymphoma cells (such as CD20, CD10, BCL2, BCL6, Ki-67) identify the subtype and possible targets for therapy.

Fluorescent in situ hybridization (FISH)

Detects gene rearrangements such as MYC, BCL2 and BCL6 ("double-hit" lymphoma) that change treatment.

Imaging tests

PET-CT is the main scan for staging most lymphomas and for checking response. CT and MRI are used in specific situations.

Bone marrow biopsy and lumbar puncture

Performed for certain subtypes or when there is a risk of spread to the marrow or central nervous system.

Staging

The Lugano system (stages I–IV) describes whether the lymphoma is in one area, on one or both sides of the diaphragm, or spread to organs outside the lymph system.

Treatment depends on the subtype, stage, how fast the lymphoma is growing, and the patient's age and health.

Treatment plans take into account:

• Lymphoma subtype and genetic features
• Stage and bulk of disease
• Symptoms and organ involvement
• Age, fitness and personal preferences

Chemotherapy and immunotherapy

Combinations such as R-CHOP or Pola-R-CHP for DLBCL, and bendamustine or other regimens for indolent lymphomas, with the anti-CD20 antibody rituximab or obinutuzumab.

Targeted therapy

BTK inhibitors, bispecific antibodies (glofitamab, epcoritamab, mosunetuzumab), antibody–drug conjugates and other new agents are used in selected and relapsed lymphomas.

Radiation therapy

Used alone for some early-stage indolent lymphomas and after chemotherapy for bulky or residual disease.

Bone marrow transplant

High-dose chemotherapy with an autologous stem cell transplant is an established treatment for relapsed aggressive lymphoma and for some mantle cell and T-cell lymphomas. Allogeneic transplant is considered in selected cases.

CAR T-cell therapy

For large B-cell, follicular and mantle cell lymphomas that relapse or do not respond, CAR T-cell therapy can produce long-lasting remissions.

Watchful waiting

Some slow-growing lymphomas without symptoms can be safely monitored until treatment is needed.

Our lymphoma specialists, hematopathologists and transplant physicians plan care together.