Non-Hodgkin’s lymphoma (NHL) is not a distinct disease but a group of lymphatic tumours, including various forms of lymphoma.
Although different types of NHL have some common characteristics, the diseases differ regarding how the cells look under a microscope, how the cancer cell grows and how the tumour influences the body.
Non-Hodgkin’s lymphomas are divided into two main types:
- B-cell lymphomas (developing from abnormal B-lymphoid cells)
- T-cell lymphomas (developing from abnormal T-lymphoid cells)
Non-Hodgkin lymphomas are also differentiated on the basis of clinical ‘behaviour’ and treatment principles:
- indolent or low-grade malignant lymphoma
- aggressive or high-grade malignant lymphoma
for example, diffuse large-cell, Burkitt and lymphoblastic lymphomas
In the case of indolent lymphoma, the patient may not need treatment at first; the patient will be monitored and the need for treatment may develop later. The aim of the treatment is keeping the disease under control for as long as possible.
Aggressive lymphomas grow very rapidly and need immediate treatment.
How non-Hodgkin’s lymphoma develops
The exact cause of the disease is not known.
Non-Hodgkin’s lymphoma may develop in any lymph node and any organ of the lymphatic system (for example, in the lymphoid tissue of the spleen, stomach or intestines).
As the lymphoid cells can move to all body parts via lymph vessels and circulation, abnormal lymphatic cells can spread throughout the body.
Although some non-Hodgkin’s lymphomas are local, some may have spread to different parts of the body by the time of diagnosis.
Most people with the mentioned risk factors will never have the disease. In some diagnosed cases, risk factors are not found.
Scientists have found several possible risk factors promoting the development of NHL.
- NHL usually occurs in people with immune system disorders:
- auto-immune diseases (chronic autoimmune thyroiditis, coeliac disease)
- immunodeficiency (severe combined immunodeficiency, hypogammaglobulinemia, HIV)
- NHL occurs somewhat more often in persons who have a family history of lymphoma, but this risk is very small.
- People who have had certain viral infections may develop NHL.
- People with HTLV (Human T-Lymphotropic virus) infection may have NHL more often than others.
- EBV (Epstein-Barr virus) has a role in the development of several types of lymphoma.
- Helicobacter pylori has been associated with the development of gastric lymphoma.
- Recently, it has been found that the hepatitis C virus may increase the probability of lymphoma.
- There seems to be a higher probability of developing NHL in people exposed to insecticides, solvents or fertilisers compared with those who are not exposed to them. At the same time, the association between them has still not been proven.
How common is non-Hodgkin’s lymphoma?
The number of annual diagnosed NHL cases in Estonia has doubled in 30 years. In 2018, 227 cases of non-Hodgkin’s lymphoma were diagnosed in Estonia (104 cases in 2004, 80 cases in 2005).1
Lymphoma incidence is higher in elderly people and in men.
Treatment of non-Hodgkin’s lymphoma
With current treatment, 45-70% of patients with aggressive or high-grade malignancy NHL can be cured.
Although NHL types with slow growth or low-grade malignancy cannot yet be cured, the prognosis of the disease is very good and patients can survive for more than 20 years.
Most NHL patients receive chemotherapy, radiotherapy, biological therapy or combinations of treatment methods. Sometimes, a bone marrow transplant or surgical operation can be used.
The biological therapy of non-Hodgkin’s lymphoma uses monoclonal antibodies (MAb), which attack cancer cells in the body. Antibodies influence the cancer cells in several ways. They recognise the cancer cell with the help of an antigen situated on the cell surface like a target and signal to the body’s immune system that the cell is abnormal and should be destroyed. Binding to the antibody hinders the development of the cancer cell and inhibits cancer growth and spread to other organs.
In the case of lymphomas, chemotherapy is currently often combined with monoclonal antibodies, so-called biological therapy, which improves treatment efficacy and increases the number of patients cured from lymphoma.
Mitte–Hodgkini lümfoomi bioloogilises ravis kasutataksemonoklonaalseid antikehasid (MAb), mis ründavad organismis vähirakke. Antikehad mõjutavad vähirakke mitmel erineval moel. Nad tunnevad vähiraku ära antigeeni järgi, mis asub rakupinnal nagu märklaud ja annavad organismi enda immuunsüsteemile märku, et rakk on ebanormaalne ja tuleb hävitada. Antikehaga seondumine takistab vähiraku arengut, pidurdab vähi kasvu ja levikut teistesse organitesse.
In the case of non-Hodgkin’s lymphoma, radiotherapy is usually applied to lymph nodes and the surrounding area.
Bone marrow transplantation
Bone marrow transplantation means the transfer of haematopoietic stem cells to the patient to restore normal haematopoiesis.
Bone marrow situated in bones contains primary cells called stem cells that develop into the cells found in blood:
- Red blood cells transporting oxygen to different parts of the body and removing carbon dioxide that has formed as residue of vital activities
- White blood cells protecting the body against inflammation
- Platelets allowing the blood to clot
How are haematopoietic stem cells obtained?
For the transplantation to succeed, it is important to obtain stem cells. Stem cells can be collected from bone marrow, peripheral blood and umbilical cord blood.
Stem cells can be obtained from another person (allogeneic transplant) or the patient’s own cells are transplanted. In this case, the sick cells have been previously removed (autologous transplant).
Before stem cell transplantation, the patient usually receives chemotherapy in very large doses with the aim of maximum (final) destruction of the tumour.
It is important to find a compatible stem cell donor as the body rejects cells that differ too much from the body’s own stem cells. The donor’s compatibility is tested with several blood indicators. Close relatives are the best donor candidates. In a HLA test, six important proteins or antigens on the surface of the white blood cells of the donor and the recipient are compared to see if the cells are compatible.
When a suitable donor for transplantation is not found among close relatives, it is possible to find the donor from the so-called registry of non-relative donors. Allogeneic transplantation is associated with serious risks; therefore, there are certain indications for allotransplantation.
Autologous transplant allows the administration of large chemotherapy (or radiotherapy) doses to the patient that cannot be used for ordinary chemotherapy due to the risk of adverse effects and thus gives a better anti-tumour effect. Most transplants (90%) in the case of lymphomas are autologous.
For example, in the case of recurrent (when the disease recurs after chemotherapy) aggressive lymphoma, full recovery is possible with autotransplantation in some patients.
In patients with indolent lymphoma, the aim of the autologous transplantation is to prolong the remission or disease-free period.
What factors influence the success of treatment?
On the basis of certain factors such as the histological type of the tumour, the patient’s age, performance status and LDH and haemoglobin levels in the blood, the spread of disease outside the lymph nodes and the disease stage, it is possible to determine the so-called prognostic index (IPI – International Prognostic Index), which helps to predict treatment success.
Age. Treatment is usually more effective in patients under 60 years of age. Younger patients tolerate the treatment better as they have less concurrent health problems (e.g. heart or lung disease) limiting treatment method or dosing.
Performance status. Performance status is a person’s ability to follow a certain way of life. Usually, better treatment results are obtained in people with good performance status (active people) than in people with poor performance status (people with chronic health problems). Patients with good performance status tolerate more intensive treatment.
Performance status is evaluated with a score from 0-4, where 0 means good and 4 poor performance status.
Blood LDH content. LDH (lactate dehydrogenase) is an enzyme in the blood. A high level of LDH can be an indicator of aggressive lymphoma. Patients with a low LDH content have better treatment results than patients with a high LDH content.
Haemoglobin level. A low haemoglobin level (<120 g/L) may indicate a worse prognosis in lymphoma patients
Extranodal disease (disease outside lymph nodes). If NHL has spread outside the lymph nodes (for example, to the bone marrow or central nervous system), the prognosis for recovery is generally worse than for patients whose disease is limited to lymph nodes.
Disease stage. Stages I and II mean local disease and stages III and IV more extensively spread or advanced disease. Chance for improvement of stages III and IV is smaller than in case of stages I and II.
Additionally, the stages are divided into A and B depending on the presence of B symptoms (fever, sweating, weight decrease).
Terms describing possible treatment result
Primary treatment is the treatment that the patient gets for non-Hodgkin’s lymphoma as an initial treatment method. Primary treatment is prescribed taking into consideration the nature of the disease as well as the patient’s age and general health status.
The following outcomes can be achieved with primary treatment:
- Complete response or remission. This term is used when all signs of disease have disappeared after treatment. It doesn’t mean that the disease has completely disappeared (although this may be the case) but that disease signs have disappeared and changes characteristic to lymphoma are not found in analyses. When treatment response persists for a long time, it is called permanent remission. The longer the patient is in remission, the better the prognosis is. As with other cancerous tumours, the disease may still come back (recur) and therefore the patient needs to be monitored for a long time.
- Cure. When there are no signs of disease recurrence, doctors can cautiously use the word ‘cure’. NHL curing chances depend on the type of lymphoma. It is possible to cure some aggressive lymphomas (complete cure). Lymphomas with a low stage of malignancy grow slowly and usually show little symptoms but may come back (recur) after a shorter or longer disease-free period (i.e. usually are not cured). Although lymphoma with a low stage of malignancy is incurable, patients usually live for years with the disease.
- Partial treatment response. This term is used when the tumour is reduced to less than half of its original size as a result of treatment.
- Poor response. This term is used when the tumour is reduced as a result of treatment, but its size is still more than half of the original size.
- Unchanged condition. The disease does not get better or worse after the treatment.
- Advancing disease. A tumour not responding to treatment.
- Disease progression. When the disease gets worse or the tumour grows during treatment, it is called disease progression or treatment failure.
Text compilation was consulted by: Dr Katrin Palk
Last updated: 16/02/2021