Hodgkin's Lymphoma

What is Hodgkin's lymphoma?

Hodgkin's lymphoma is a distinct cancer of lymphoid tissue derived from germinal B cells of lymph glands, defined by the presence of very characteristic cells called REED-STERNBERG cells or its variants with characteristic immunophenotype in a background of different types of cells.

What are the types of Hodgkin's lymphoma?

• Nodular sclerosing HL
• Mixed-cellularity subtype
• Lymphocyte-rich or Lymphocytic predominance
• Lymphocyte depleted
• Nodular lymphocyte predominant Hodgkin’s lymphoma (NLPHL)

What are the Symptoms of Hodgkin’s lymphomas?

• Painless swelling of the lymph nodes in neck, armpits, groin (swollen glands)
• Fatigue
• Fever and chills that come and go (380C / 100.4 F)
• Unexplained Itching all over the body
• Loss of appetite
• Soaking night sweats
• Unexplained Weight loss

Other symptoms that may occur with this disease:

• Coughing, chest pains, or breathing problems if there are swollen lymph nodes in the chest
• Excessive sweating
• Pain or feeling of fullness below the ribs due to swollen spleen or liver
• Pain in lymph nodes after drinking alcohol
• Skin blushing or flushing

What Causes Hodgkin's lymphoma?

• The exact cause of Hodgkin disease is not known
• Most Hodgkin's lymphomas occur when an infection-fighting cell called a B cell develops a mutation in its DNA.

What are the factors that increase the risk of Hodgkin's lymphoma?

• Age: Generally Age group 15-35 and 55 years and above are diagnosed with Hodgkin's lymphoma
• Sex: Mostly Male are suspected to be on higher risk of Hodgkin's lymphoma
• Previously exposed to the Epstein-Barr virus (EBV), a common virus that causes glandular fever
• Medical condition that weaken immune system, such as HIV
• Previous treatment with chemotherapy or radiotherapy for Non-Hodgkin’s Lymphoma

How do we diagnose Hodgkin lymphomas?

• Lymph node biopsy: Hodgkin's lymphoma is diagnosed from Biopsy of lymph gland or other involved tissues.
• Histopathology reveals five subtypes: Nodular Sclerosis and Mixed cellularity are more common. The other varieties are Lymphocyte Depleted and Nodular Lymphocyte Predominant Hodgkin's lymphoma (NLPHL).
• Detection of cell surface antigens by Immunohistochemistry (IHC) is confirmatory. Expression of CD30 and CD15 are seen in the RS cells, except in NLPHL, where these cells express CD20 rather than CD30 or Cd15.
• Blood tests: Sample of blood is examined in a lab to see if anything in the blood indicates the possibility of cancer. e.g. a low haemoglobin, low platelet counts and may be raised eosinophil etc.
• Imaging tests: Imaging tests used to diagnose Hodgkin's lymphoma include X-rays, computerized tomography (CT) scan, magnetic resonance imaging (MRI) and positron emission tomography (PET).
• Bone Marrow Biopsy: This is necessary to ascertain the extent of the disease. Rarely, the presentation is with Bone Marrow Involvement alone.
• Additional Tests: Serum LDH, ECG, Echocardiogram and Lung Function Test before starting treatment.

How is Hodgkin disease staged?

• Stage I: Hodgkin disease is found in only 1 lymph node area or lymphoid organ such as the thymus (I). The cancer is found only in 1 area of a single organ outside the lymph system (IE).
• Stage II: Hodgkin disease is found in 2 or more lymph node areas on the same side of (above or below) the diaphragm — the muscle beneath the lungs that separates the chest and abdomen (II). The cancer extends locally from one lymph node area into a nearby organ (IIE).
• Stage III: Hodgkin disease is found in lymph node areas on both sides of (above and below) the diaphragm (III). Hodgkin disease is in lymph nodes above and below the diaphragm, and has also spread to a nearby organs (IIIE), to the spleen (IIIS), or to both (IIIES).
• Stage IV: Hodgkin disease has spread widely through 1 or more organs outside of the lymph system. Cancer cells may or may not be found in nearby lymph nodes. Hodgkin disease is found in organs in 2 distant parts of the body (and not in nearby lymph nodes). Hodgkin disease is in the liver, bone marrow, lungs (other than by growing there directly from another site), or cerebrospinal fluid (the fluid that surrounds the brain and spinal cord).

How is Hodgkin disease treated?

Several types of treatment options are available for Hodgkin disease:

• Chemotherapy
• Radiation therapy
• High-dose chemotherapy and Bone Marrow transplant
• Favourable, Limited Stage Disease: Treated with short course chemotherapy and involved field radiotherapy; >95% cure rate.
• Unfavourable, Limited Stage Disease: Similar treatment but more intensive; > 90% cure rate
• Advanced Disease: ABVD/BEACOPP >60%-80% cure rates.

However, use of radiotherapy is not favoured in small children unless absolutely necessary.

BMT for Hodgkin's lymphoma

What to do when Hodgkin's lymphoma recurs?

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

Once Hodgkin's lymphoma relapses, the treatment is well-defined and is 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.

Is there any role of BMT upfront?

If a patient achieves a complete remission, even in advanced disease, there is no need to perform an Autologous BMT upfront. However, when the disease does not remit completely or even progresses and is not sensitive to first line chemotherapy, Autologous BMT might cure 20-30% of such patients.

When is Allogeneic BMT needed for Hodgkin's lymphoma?

• When the disease recurs after Autologous BMT
• When PBSC cannot be mobilised for Autologous BMT

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

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

70% patients are cured with this procedure.