Non Hodgkin's Lymphoma

What is Non-Hodgkin’s Lymphoma (NHL)?

Lymphoma begins when B cells, T cells, or NK cells in the lymphatic system change and grow uncontrollably, which sometimes may form a tumor. Hodgkin lymphoma is a specific type of lymphoma that is covered in another section of this website. Non-Hodgkin lymphoma (NHL) is a term that refers to the many other types of cancer of the lymphatic system, which can have different symptoms and signs, physical findings, and treatments.

Because lymphatic tissue is found in most parts of the body, NHL can start almost anywhere and can spread to almost any organ. It most often begins in the lymph nodes, liver, spleen, or bone marrow, but it can also involve the stomach, intestines, skin, thyroid gland, brain, or any other part of the body.

It is very important to know which type and subtype has been diagnosed because this information helps doctors determine the best treatment and a patient’s prognosis (chance of recovery).

Non-Hodgkin’s Lymphoma is more common in adults than children.

What Causes Non-Hodgkin’s Lymphoma and what are the risk factors?

Certain types of Non-Hodgkin’s Lymphoma are caused or triggered by Infections. Most common causes are as under :-

• EBV and Burkitts lymphoma
• Hepatitis C
• HTLV1
• Helicobacter Pylori causing lymphoma of the stomach.
• HIV infection increases the incidence of high grade lymphomas
• Long term intake of drugs suppressing the immune system as after solid organ transplants
• Primary immunodeficiency and autoimmune diseases
• Chemicals: polychlorinated biphenyls (PCBs), diphenylhydantoin, dioxin, and phenoxy herbicides.
• Medical treatments: like radiation therapy and chemotherapy
• Genetic diseases, like Klinefelter's syndrome, Chédiak-Higashi syndrome, ataxia telangiectasia syndrome
• Autoimmune diseases, like Sjögren’s syndrome, celiac sprue, rheumatoid arthritis, and systemic lupus erythematosus.

What are the risk factors for Non-Hodgkin’s Lymphoma?

• Being male: Non-Hodgkin’s Lymphoma is more common in men than in women.
• Age: Likelihood of getting Non-Hodgkin’s Lymphoma increases with age.
• Impaired immune system: NHL is most common among those who have an impaired immune system, an autoimmune disease, or HIV or AIDS. It also occurs among those who take immunosuppressant medicines, such as medicines following an organ transplant.
• Viral infections: A viral infection, such as Epstein-Barr virus, increases the risk of developing NHL.
• Bacterial infections: Infection with Helicobacter pylori increases the risk of lymphoma involving the stomach.
• Environmental exposure: Exposure to agricultural pesticides or fertilizers, solvents, and other chemicals may increase the risk of developing NHL.

What are the Symptoms?

The symptoms are protean. They range from painless lymph node enlargement to fits and paralysis. Most patients have ‘B symptoms’ defined by

• A painless swelling of the lymph nodes in the neck, underarms, or groin. This is the most common symptom.
• Fever above 380C (100.4 F)
• Drenching Night sweats.
• Feeling very tired.
• weight loss > 10% of baseline body weight
• Itchy skin.
• Reddened patches on the skin.
• A cough or shortness of breath.
• Pain in the belly or back.

How do we Diagnose Non-Hodgkin’s Lymphoma?

Biopsy and Histopathology

NHL is diagnosed from Biopsy of lymph gland or other involved tissues. Fine Needle aspiration Cytology (FNAC) might broadly categorise the disease as lymphoma, but further sub-classification is difficult.

• Histopathological diagnosis reveals two major subtypes: T cell Non-Hodgkin’s Lymphoma and B cell Non-Hodgkin’s Lymphoma.
• B cell Non-Hodgkin’s Lymphoma is more common
• This is further classified as HIGH GRADE and LOW GRADE
• Detection of cell surface antigens by Immunohistochemistry (IHC) is confirmatory.
• Complete Blood Count: Aanemia and Thrombocytopenia may be seen. Eosinophil count is often raised
• Bone Marrow Biopsy: This is necessary to ascertain the extent of the disease. Rarely, the presentation is with Bone Marrow Involvement alone.
• PET-CT Scan: This has revolutionised the diagnosis and management of NHL. In the early days, surgery was performed to find the extent of the disease in the abdomen. With the advent of Contrast-enhanced CT Scan, the need for surgery was obviated. However, the response of the disease was measured by complete disappearance of enlarged glands. Many a time this did not happen and a repeat biopsy was needed. PET scan allow us to see the metabolic activity in the affected areas and disappearance of NHL will be marked by absence of metabolic signal previously seen at the time of diagnosis.
• Additional Tests: Serum LDH, ECG, Echocardiogram and Lung Function Tests are done before starting treatment.

How do we treat Non-Hodgkin’s Lymphoma?

Treatment plans are designed to meet the unique needs of each person with lymphoma. Treatment decisions for non-Hodgkin lymphoma (NHL) are based on:

• the type of NHL
• the stage of NHL
• how quickly the NHL is growing (grade) – whether it is slow growing (indolent) or fast growing (aggressive)
• prognostic factors
• person's age
• person's overall health status and if he has other medical conditions that may interfere with treatment
• previous treatment, if any

General Principles

HIGH GRADE B CELL NHL: Chemotherapy called R-CHOP regimen remains the gold standard for primary treatment.

However, based on GENE EXPRESSION PROFILE, Diffuse large B cell Lymphoma (DLBCL) is classified in three groups, GCB, ABC and PMBCL. The latter two do not respond as well to CHOP and might benefit from alternate combinations.

However, we do not favour use of radiotherapy in small children unless absolutely necessary.

LOW GRADE B CELL NHL: These lymphomas occur exclusively in older individuals and are treated in the same way as CLL.

T CELL NHL: They are mostly high grade and some of them are triggered by HTLV-1 virus. The response to CHOP is less encouraging. This group of patients require early BMT.

Treatment options for NHL OTHER THAN BMT

• Chemotherapy - The chemotherapy drugs used depend on the type and stage of NHL being treated. Single chemotherapy drugs or combinations of chemotherapy drugs are often used to treat NHL.
• Biological therapy - Biological therapy may be used on its own to treat certain types and stages of NHL. It may also be used in combination with chemotherapy.
• Radiation therapy - External beam radiation therapy may be used on its own to treat localized areas of early stage lymphoma. It may also be used along with chemotherapy as part of a combination of treatments. However, Radiation Therapy is not recommended in children unless absolute necessary.
• Surgery - Surgery is mainly used to remove all or part of a lymph node (biopsy) to diagnose lymphoma. More extensive surgery is rarely used to treat NHL. The spleen may be removed (splenectomy) in certain situations.
• Follow-up after completing the treatment - It is important to have regular follow-up visits, especially during the first 2 years after treatment, because that is when the risk of recurrence is greatest.

Role of BMT in the treatment of Non-Hodgkin’s Lymphoma

What to do when Non-Hodgkin’s Lymphoma recurs?

About 30% patients with advanced disease and 10% patients with Limited disease relapse.

Once Non-Hodgkin’s Lymphoma relapses, the treatment is well-defined and as follows:

• Salvage Chemotherapy
• Autologous Peripheral Blood Stem Cell Collection
• High Dose Chemotherapy and Autologous BMT

What is the cure rate with Autologous BMT?

If the patient is PET negative before BMT, 80% of the patients are cured. If the patient is PET positive before BMT, only 50% patients are cured.

When is upfront BMT required?

• Patients with more advanced disease
• T cell NHL
• MantleCell Lymhoma

When is Allogeneic BMT needed for Non-Hodgkin’s Lymphoma?

• When the disease recurs after Autologous BMT
• When Peripheral Blood Stem Cells cannot be mobilised for Autologous BMT
• T cell NHL
• Relapsed Low Grade NHL
• Relapsed Mantle Cell Lymphoma

There is a strong Graft versus Tumour effect against NHL in the setting of Allogeneic BMT

In the setting of High Risk and Relapsed NHL, best results are obtained with HAPLOIDENTICAL DONOR and REDUCED INTENSITY CONDITIONING.

70% patients are cured with this procedure.

The children have more aggressive varieties of NHL. The cure rates in children are much higher.