Non-Hodgkin Lymphoma: Description

Brief overview

  • Description: Non-Hodgkin’s lymphoma is an umbrella term for certain cancers of the lymphatic system.
  • Symptoms: General symptoms such as painless swollen lymph nodes, fever, weight loss, profuse night sweats, fatigue, itching.
  • Prognosis: Low-malignant NHL is usually curable only in early stages; high-malignant NHL is in principle curable in all stages with the right treatment.
  • Examinations and diagnosis: taking the patient’s history, physical examination, blood and tissue tests; imaging procedures to examine tumor spread.
  • Treatment: depending on the type and stage of the disease, e.g. Watch & Wait, radiotherapy, chemotherapy, antibody therapy, CAR-T cell therapy or stem cell transplantation, if necessary.

What is non-Hodgkin’s lymphoma?

Non-Hodgkin’s lymphoma occurs at all ages, but older people are more susceptible.

The lymphatic system

The lymphatic system, which is distributed throughout the body, consists of the lymphatic vascular system and lymphoid organs such as the bone marrow, thymus, spleen, tonsils and lymph nodes. It collects and transports excess tissue fluid – lymphatic fluid or lymph for short.

B lymphocytes (B cells) are primarily responsible for producing antibodies against invading pathogens. T lymphocytes (T cells), on the other hand, directly attack pathogens in the body and direct the defense response.

Classification into B- and T-cell lymphomas

B-cell lymphomas are by far the more common group: about eight out of ten non-Hodgkin lymphomas derive from B lymphocytes or their precursor cells.

Lymphoma cells circulating in the blood often get “stuck” in a lymph node, where they take hold and continue to multiply. Therefore, non-Hodgkin’s lymphomas usually originate in lymph nodes.

Classification according to malignancy

  • Low-malignant (indolent) non-Hodgkin’s lymphomas: They develop slowly over years to decades. As a result, therapy here is usually not as effective as with faster-growing (highly malignant) forms of NHL.

Overview: Types of Non-Hodgkin Lymphoma

Here is a tabular overview of selected B-cell and T-cell non-Hodgkin lymphomas:

B-cell non-Hodgkin lymphoma

T-cell non-Hodgkin’s lymphoma

low-malignant

high malignant

What are the symptoms of non-Hodgkin’s lymphoma?

Non-Hodgkin’s lymphoma symptoms vary depending on the course of the disease. However, there are common symptoms that occur very often: For example, permanently or increasingly enlarged, painless lymph nodes are typical of non-Hodgkin’s lymphoma. Mainly lymph nodes in the neck are affected, but often also others, for example those in the armpit, groin, chest and abdomen.

The general symptoms include other complaints that physicians summarize under the term B-symptomatics:

  • Fever or episodes of fever: Increase in body temperature to over 38 °C without an obvious cause such as an infection.
  • Night sweats: heavy sweating during the night, which often causes sufferers to wake up “soaking wet,” change into their pajamas, and change into a new bed.
  • Weight loss of more than ten percent of body weight within six months

Itchy skin all over the body can also be observed in some patients. The exact causes of itching are not yet known. It is possible that the degenerated blood cells release chemical substances near the sensitive skin nerves and thus trigger the itching.

All these symptoms are not characteristic of non-Hodgkin’s lymphoma, but can also have other causes! For example, lymph nodes are also swollen during infections, but then hurt during palpation and quickly shrink again after the infection. B-symptomatics can also occur with other cancers as well as other serious diseases such as tuberculosis.

What is the life expectancy with non-Hodgkin’s lymphoma?

In principle, the degree of malignancy plays a particularly important role here:

Highly malignant NHL with its high cell division rate responds much better to treatment. In principle, a cure is therefore possible at all stages of the disease.

In individual cases, however, other factors influence the prognosis for non-Hodgkin’s lymphoma. Life expectancy and the success of treatment depend, for example, on the age and general condition of the patient and on whether and how many cancer foci are present outside the lymph nodes.

What causes non-Hodgkin’s lymphoma?

Risk factors discussed or known include the following:

Infections

Some non-Hodgkin’s lymphomas develop in association with certain infections. For example, Epstein-Barr virus (EBV) contributes to the development of certain forms of Burkitt lymphoma. This is a highly malignant B-cell non-Hodgkin lymphoma. However, this virus is better known as the causative agent of Pfeiffer’s glandular fever (mononucleosis).

Mucosa-associated lymphoid tissue (MALT) lymphoma originates from lymphoid tissue of the mucosa and most commonly arises in the stomach. It is then a rare form of gastric cancer. It often develops based on chronic infection with the gastric germ Helicobacter pylori.

Adult T-cell lymphoma (ATLL) develops in association with so-called HTL viruses (human T-lymphotropic viruses).

Earlier cancer therapy

Immunosuppressive therapy

After an organ transplant or in the case of HIV infection, patients receive drugs that suppress the immune system. These immunosuppressive drugs may promote the development of lymphoma.

Toxins

Weed killers (herbicides) are also discussed as possible triggers of non-Hodgkin’s lymphoma.

Diseases of the immune system

It is possible that some diseases of the immune system promote the occurrence of NHL. For example, there are indications of rheumatoid arthritis, Sjögren’s syndrome, lupus erythematosus, celiac disease, and some congenital or acquired immunodeficiencies such as Wiscott-Aldrich syndrome or HIV.

How is non-Hodgkin’s lymphoma diagnosed?

Medical history and physical examination

The first step in the clarification of symptoms is a detailed doctor-patient consultation to obtain a medical history (anamnesis). Among other things, the doctor will ask about your exact symptoms and any previous or underlying diseases. Possible questions include:

  • Have you noticed any swelling in your neck?
  • Have you woken up sweaty at night lately?
  • Have you lost body weight unintentionally in the last few months?
  • Have you had frequent nose or gum bleeds lately?

The interview is usually followed by a physical examination. Among other things, the doctor will palpate your lymph nodes (for example, on your neck) and spleen for enlargement.

Blood tests

If the number of red blood cells (erythrocytes) is reduced, doctors call this erythrocytopenia. This usually leads to anemia. The level of blood platelets (thrombocytes) sometimes also drops sharply (thrombocytopenia), increasing the tendency to bleed.

Whether the lymphocyte subgroup is responsible for this increase can be seen in the so-called differential blood count. This indicates the percentage of the various leukocyte subgroups such as lymphocytes and monocytes. The differential blood count is therefore very informative when CLL or another form of NHL is suspected.

  • Mature B lymphocytes carry the protein CD20 on their surface even when they develop into cancer cells (B lymphoma cells). Then this protein is found in even higher numbers on the cell surface.
  • In contrast, the surface protein CD3 is typical for T lymphocytes and the cancer cells that develop from them (T lymphoma cells).

This enzyme is found in different variants in most organs of the body and is usually elevated in the presence of a tumor. If its concentration rises, this indicates increased cell death. For this reason, it is also used to monitor the progress of tumor treatment.

Tissue examinations

Imaging procedures

If the suspicion of non-Hodgkin’s lymphoma is confirmed by tissue examinations, imaging procedures help the doctor to find out how far the cancer has already spread in the body. To do this, he uses X-rays and ultrasound scans, for example, as well as computed tomography (CT) and sometimes positron emission tomography (PET). The results help determine the stage of non-Hodgkin’s lymphoma (“staging”).

Physicians generally divide non-Hodgkin’s lymphomas into four tumor stages according to Ann-Arbor (modified after Cotswold (1989) and Lugano (2014)) based on their spread in the body. Only chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) use other classifications for staging.

The Ann Arbor staging provides that the further a non-Hodgkin’s lymphoma has already spread in the body, the higher the tumor stage.

Stage

Tumor spread

I

II

Involvement of two or more lymph node regions or localized extranodal foci – but only on one side of the diaphragm (i.e., either in the chest or abdomen)

III

Involvement of two or more lymph node regions or localized extranodal foci – buton both sides of the diaphragm (i.e. both in the chest and abdomen)

IV

What is the therapy for non-Hodgkin’s lymphoma?

Non-Hodgkin’s lymphoma therapy depends primarily on whether it is low-malignant or high-malignant NHL. This is generally more important than tumor stage. Other factors that influence the planning of therapy include a patient’s age and general condition.

Therapy for low-malignant NHL

In more advanced stages (III and IV), low-malignant NHL can usually no longer be cured. Then there are generally two options:

  • “Watch-and-wait” strategy: Doctors often do not treat a very slow-growing tumor, but initially only monitor it closely – for example, if the non-Hodgkin’s lymphoma does not (yet) cause any symptoms.

This antibody therapy supports the immune system in its fight against cancer. It is thus one of the so-called immune therapies.

Therapy for highly malignant NHL

As with low-malignant forms, physicians usually combine this chemotherapy with rituximab (antibody therapy) if the cancer is B-cell lymphoma.

CAR T-cell therapy

If the therapeutic measures described above do not help or patients relapse, CAR T-cell therapy is sometimes used. This is a new form of immunotherapy that works as follows:

  • First, healthy T lymphocytes (T cells) are filtered out of the blood of the patient.
  • Now the patient receives chemotherapy to reduce the number of lymphoma cells and dampen the activity of the immune system. This later makes it easier for the CAR-T cells to do their work.
  • In the next step, the patient receives the CAR-T cells by infusion. In the body, thanks to their specific docking sites (CAR), these cells bind specifically to the tumor cells and destroy them.

Special therapy approaches

For some forms of non-Hodgkin’s lymphoma, doctors use special therapeutic approaches. Example:

Patients receive chemotherapy and/or targeted therapy (with rituximab or other artificially produced antibodies or so-called signal pathway inhibitors). In individual cases, stem cell transplantation or radiation therapy is also useful.

Read more about the treatment of CLL here.