Non-Hodgkin's Lymphoma

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.

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

• 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.

Risk Factors

• 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 other viral infections.
• 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 getting NHL.

The symptoms are protean. They range from painless lymph node enlargement to fits and paralysis. Most commonly, patients present with 'B symptoms' defined by:

• A painless swelling of the lymph nodes in the neck, underarms, or groin. This is the most common symptom of NHL.
• Fever above 38°C (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.

Biopsy and Histopathology

NHL is diagnosed from Biopsy of lymph gland or other involved tissues. Fine Needle aspiration Cytology (FNAC) is not enough for diagnosis of Lymphoma.

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: Anemia 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 and Blood involvement.

PET-CT Scan: This has revolutionised the diagnosis and management of NHL. In the early days, surgery was performed to stage the disease.

Additional Tests: Serum LDH, ECG, Echocardiogram and Lung Function Tests are done before starting treatment.

Treatment plans are designed to meet the unique needs of each person with lymphoma. Treatment decisions are made depending on: the type of NHL; the stage; how quickly the NHL is growing (grade); prognostic factors; person's age; person's overall health status; 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 groups have a poorer outcome and require upfront BMT. 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 Other Than BMT

• Chemotherapy: Single chemotherapy drugs or combinations of drugs can be given.
• Biological therapy: May be used on its own or in combination with chemotherapy.
• Radiation therapy: External beam radiation therapy may be used on its own to treat localized areas of early stage lymphoma.
• Surgery: Surgery is mainly used to remove all or part of a lymph node (biopsy) to diagnose lymphoma.
• Follow-up: It is important to have regular follow-up visits, especially during the first 2 years after treatment.

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:

1. Salvage Chemotherapy
2. Autologous Peripheral Blood Stem Cell Collection
3. High Dose Chemotherapy and Autologous BMT

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, the cure rate is only 20%.

When is Upfront BMT Required?

• Patients with more advanced disease
• T cell NHL
• Mantle Cell Lymphoma

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 toxicity transplantation. 70% patients are cured with this procedure. The children have more aggressive varieties of NHL. The cure rates in children are much higher.