Lymphoma is cancer of the lymphatic system. The lymphatic system consists of lymph nodes present all over the body, the lymph vessels that connect these lymph nodes with each other. Organs such as the spleen, thymus gland, bone marrow and tonsils are also part of the lymphatic system. Lymphocytes, which are white blood cells present in the blood and bone marrow are also part of the lymphatic system.
The function of the lymphatic system is to drain fluid from the organs and to protect the body from infections. When infection is present in a part of the body, the lymph nodes in that area try and stop the infection from spreading to other parts of the body. This can lead to enlargement of the lymph nodes as seen commonly.
There are two main types of lymphoma. One is called as Hodgkins lymphoma and the other one is called as Non Hodgkins Lymphoma.
Hodgkins lymphoma is named after the person who discovered the condition. When seen under the microscope, this lymphoma contains a type of cell called Reed sternberg cell. This lymphoma presents and behaves differently to other lymphomas and is treated differently to a Non Hodgkins lymphoma. It makes about 20% of all lymphomas.
Hodgkins lymphoma can again be of many types depending on how it looks under the microscope. These can be classified as
- Classical Hodgkins Lymphoma
- Nodular sclerosing
- Mixed cellularity
- Lymphocyte predominant
- Lymphocyte depleted
- Nodular lymphocyte predominant type
According to Globocan data 2018, there were 9115 new Hodgkin lymphoma cancers in India in 2018, making up 0.79% of all cancers.
Hodgkins Lymphoma can produce a number of symptoms. In patients with early disease, symptoms may be minimal or absent.
Swelling and Enlargement of Lymph nodes
A common symptom seen is enlargement of lymph glands in the body. This can be in the area of the neck, under the arm pit, groins or in other parts of the body such as in the chest or stomach. These swellings are usually painless but can occasionally cause pain. Lymph nodes can enlarge due to a number of reasons including infections and not always due to a lymphoma.
Other symptoms commonly associated with Hodgkins lymphoma include fever, loss of weight, excessive sweating at night, itchy skin, cough, difficulty breathing or stomach pains.
Symptoms due to anaemia or symptoms such as bruising, bleeding or infections can happen if there is involvement of the bone marrow by Hodgkins lymphoma.
When a lymphoma is suspected, either a Hodgkin or a Non-Hodgkin lymphoma, the following investigations are usually done.
A biopsy of the enlarged lymph node is done to confirm the presence of a lymphoma. This is either a core biopsy (core of a lymph node) or an excision biopsy where the entire lymph node is removed. Another type of biopsy called FNAC is not done in this setting. Immunohistochemistry (IHC) markers are special tests done on the biopsy sample to identify the specific type of lymphoma. Sometimes, a number of IHC markers are tested to know the exact type of lymphoma and to determine the right treatment. If a lump or a mass is present separate to a lymph node, a biopsy of the lump is done. Genetic tests to look for abnormalities in the chromosomes are sometimes done to confirm the presence or absence of a certain type of lymphoma.
CT scan or PET-CT scan
A CT scan or a PET-CT scan is an ideal test to look for the extent of spread of the lymphoma. The scan is used to help in the staging process of the condition and will give information as to where the cancer is present in the body. A PET-CT scan is better than a CT scan to diagnose and stage the lymphoma. These scans are also done in patients having chemotherapy for lymphoma, to see how well the cancer is responding to treatment.
Bone Marrow Biopsy
A bone marrow biopsy involves taking a sample of cells from the marrow of the bone. This is an important test in lymphoma to look for spread of this cancer into the bone marrow. This biopsy is done under local anaesthesia. A bone marrow test may not be done in patients where a PET-CT scan does not show any disease in the marrow.
A number of blood tests such as CBP, ESR, LDH, Liver function tests, Creatinine, Electrolytes and others are done routinely to assess the functions of various organs.
Other tests such as X rays, Ultrasound scan of the abdomen, MRI scans may also be used in some situations to gain more information about the disease. A lumbar puncture where a needle is placed in the spine to get a sample of fluid is done in some situations.
In stage 1, there is Involvement of a single lymph node region (I) or of a single extra lymphatic organ or site (IE) without lymph node involvement. A single lymph node region can include one node or a group of adjacent nodes.
In stage 2, there is involvement of two or more lymph node regions on the same side of the diaphragm (muscle separating chest and abdomen) alone (II) or with involvement of limited, contiguous organ or tissue that is not a lymph node (IIE).
In stage 3, there is involvement of lymph node regions or lymphoid structures on both sides of the diaphragm.
In stage 4, there is additional non-contiguous extra lymphatic involvement, with or without associated lymphatic involvement.
All lymphomas are sub classified to indicate the absence (A) or presence (B) of one or more of the following three symptoms: unexplained fevers to more than 101°F, drenching night sweats, or unexplained weight loss exceeding 10 percent of body weight during the six months prior to diagnosis. Fatigue, itching, and alcohol-induced pain are not considered B symptoms but should be noted.
The treatment of Hodgkin lymphoma is dependent on a number of factors such as stage, sub type of Hodgkin lymphoma, patient’s age and general fitness.
Early stage Hodgkin Lymphoma
Early stage Hodgkin lymphoma is treated with a combination of chemotherapy and Radiotherapy. The chemotherapy is usually with a treatment called ABVD. This is a combination of 4 drugs called Doxorubicin, Bleomycin, Vinblastine and Dacarbazine. It is given in the vein for 2-4 cycles, each cycle lasting 28 days. In the 28 days, treatment is given twice, on day 1 and day 15. This is followed by Radiotherapy. Radiotherapy for early stage lasts for 2-3 weeks.
Advanced stage Hodgkin Lymphoma
Advanced stage Hodgkin lymphoma is treated mainly with Chemotherapy. Usually ABVD treatment is used for 4 cycles. Sometimes, other chemotherapy regimens are used depending on the condition of the patient.
Radiotherapy is used in some settings as a consolidation treatment after completion of chemotherapy.
Relapsed or Refractory Hodgkin Lymphoma
When the disease comes back after being controlled with initial treatment, it is called as relapsed disease. When the disease does not respond or only responds partially to treatment, it is called as refractory disease.
In situations where there is relapsed or refractory disease, a different chemotherapy option is used and if the patient is physically fit, a bone marrow transplant is considered.
Chemotherapy is an important part of treatment of Hodgkin lymphoma. Chemotherapy in this condition is given in different forms. The different types of treatments used are listed below. Some of these regimens are used as first line treatments, that is at the time of diagnosis and others are used when the lymphoma has recurred after initial treatment.
This is a common regimen of chemotherapy used in Hodgkin Lymphoma particularly in early stage disease. ABVD stands for four drugs, Adriamycin (Doxorubicin), Bleomycin, Vinblastine and Dacarbazine. This treatment is given as cycles, each cycle lasting 28 days. In the 28 days, treatment is given on day 1 and day 14. Up to 2-4 cycles are given depending on the stage of disease.
This is another type of chemotherapy used mainly in higher stage disease. This regimen consists of seven drugs including Doxorubicin, Vinblastine, Vincristine, Mustine, Etoposide, Bleomycin and steroids.
This regimen consists of Bleomycin, Etoposide, Doxorubicin, Cyclofosfamide, Vincristine, Procarbazine and Prednisolone.
This type of chemotherapy contains Chlorambucil, Vinblastine, Procarbazine and Prednisolone.
This chemotherapy consists of Gemcitabine, Cisplatin and Prednisolone and is used to treat disease that has relapsed.
This treatment consists of Cisplatin, Cytarabine, Etoposide and Prednisolone and is used to treat disease that has relapsed.
This treatment consists of Mustine, Etoposide, Cytarabine and Melphalan and is used prior to Stem Cell transplant.
Side effects of chemotherapy
Chemotherapy for lymphoma is associated with side effects. These depend on the drugs that are administered. Some of these side effects can be well controlled with medications. Tolerability of chemotherapy varies from person to person. Some people cope with treatment very well without any side effects, while other may have side effects. common side effects are
This is common with the mentioned chemotherapy regimens. Hair loss usually starts after the second week of the first cycle. Hair grows back after chemotherapy is finished
Nausea and vomiting
This is a well-known side effect of chemotherapy, but with modern medications, these symptoms are very well controlled. Nausea is the sensation of feeling like vomiting.
Tiredness is a common side effect. It is usually more in the first week and then gradually improves after that.
Soreness in the mouth
This is common after chemotherapy and will settle by itself.
This symptom can occasionally occur after chemotherapy.
Constipation is a common side effect of chemotherapy. This can happen as a result of the chemotherapy drug itself but mainly it is due to the effect of the anti-vomiting drugs that are given along with chemotherapy. Constipation happens in the first few days of chemotherapy.
Risk of Infection
This is an important side effect of chemotherapy. It happens as chemotherapy reduces the capacity of the body to fight infections. Therefore, it is very important to contact your doctor urgently if you have a fever at any time (even if it is in the middle of the night) during chemotherapy.
This is common with chemotherapy and therefore food wont taste as before. Taste will recover after chemotherapy is finished.
Tingling in Hands and feet
Some chemotherapy drugs produce this side effect.
This can happen as a result of chemotherapy. Usually this can just be observed and it will improve after treatment finishes. Sometimes blood transfusion or other treatment is necessary to improve it.
There is a small risk of bleeding with chemotherapy. If this happens, you need to contact your doctor straight away.
Hodgkin lymphoma is common in young people and one potential side effect is reduced fertility in man and women. As a result of chemotherapy, the function of the ovaries in a female and the sperm production in a male can be reduced. This function can recover after chemotherapy is completed but it is advised for young patients planning to have children in the future to consult a fertility specialist to discuss options prior to start of chemotherapy. Such options include storage of sperm (sperm banking) in a male and oocyte preservation in a female.
In older adults particularly those in late 40’s or early 50’s there is a risk of early menopause after chemotherapy as the ovary function does not recover after completion of chemotherapy.
Cough and Breathlessness
This is a potential side effect of ABVD chemotherapy due to the drug Bleomycin. This drug can cause side effects related to the lung such as cough and shortness of breath. If such side effects occur, the doctor should be informed quickly.
Radiotherapy is used as a treatment in Hodgkin Lymphoma in different settings.
Early stage Hodgkin Lymphomas
In early stage lymphomas, radiotherapy is used after chemotherapy is completed. Radiotherapy is given for about 2-3 weeks duration and the side effects with this treatment are minimal. The treatment is given to the area where the lymphoma was found prior to start of chemotherapy. Possible side effects of radiotherapy in Hodgkin lymphoma will include tiredness, mild skin redness in the area treated and other side effects depending on the area of the body that is being treated.
Advanced Stage Hodgkin Lymphoma
In advanced stage Hodgkin lymphomas, radiotherapy is sometimes used as consolidation treatment after completion of chemotherapy. This is particularly used in situations where the lymphoma was large at the time of diagnosis or there is lymphoma still present in an area after completion of chemotherapy.
In other situations, with advanced disease, radiotherapy may be used to control local symptoms such as pain etc.
Bone marrow transplant or stem cell transplant is a type of treatment used in Hodgkin lymphoma when the cancer has come back (relapsed) after initial treatment or the disease does not go away with initial chemotherapy.
Prior to having a bone marrow transplant, the patient is given a high dose of chemotherapy, for example a regimen of chemotherapy like BEAM. The aim of this chemotherapy is to kill off all lymphoma cells. As this chemotherapy is high dose, it kills off normal cells present in the bone marrow also.
The function of the bone marrow normally is to produce blood cells such as red blood cells which help the blood to carry oxygen, white blood cells which protect against infections and platelets which help stop bleeding. A significant lowering of these cells in the blood is dangerous to the patient and hence a transplant of these cells is needed after a high dose of chemotherapy.
Collection of Stem Cells
Stem cells are a type of blood cells that have the capacity to develop into any kind of blood cell such as red blood, white blood cell or platelets. These stem cells are present in the blood stream and bone marrow and are initially collected from the patient before the patient receives high dose chemotherapy. This process of collection of stem cells from the patient and infusing them back into the same patient after high dose chemotherapy is called as Autologous Stem cell transplant.
If the stem cells are from another person(donor), then it is called an Allogenic stem cell transplant. The donor can be related, usually a brother or a sister, or unrelated but matched donor. A donor may be used in situations when there is cancer present in the marrow or an Autologous transplant was done before, but the disease has relapsed again.
Before collection of stem cells, the patient may have chemotherapy and injections with G-CSF which will increase the number of stem cells in the blood to achieve a successful collection.
On the day of collection of stem cells, the patient is connected to a machine and the patient’s blood is taken out from one vein and it passes through the machine to collect the stem cells present in the blood. The blood then passes back into the patient through another vein. This process is done over a few hours.
Once the stem cells are collected, the patient receives the high dose chemotherapy. After the chemotherapy, the stem cells are infused back into the patient. These cells go into the bone marrow and start making blood cells again.
Stem cell transplant is more commonly used these days as compared to bone marrow transplant.
Collection of bone marrow
Bone marrow is the spongy material that is present inside the bones. For a bone marrow transplant, the marrow needs to be collected prior to giving high dose chemotherapy. The procedure to collect the marrow is done under general anaesthesia usually in an operation theatre. The marrow may be taken out from different places in the bones and about 1 litre of it may be taken out at the procedure. Once taken out, it is stored and infused into the patient when needed.
Risks and side effects of Stem cell and Bone marrow Transplant
Having a stem cell or bone marrow transplant is a complex process and is associated with side effects. This procedure usually involves staying in hospital for a few weeks for the blood cells in the marrow and blood to recover to normal levels after the transplant is done. Common side effects associated with this procedure include
Nausea, Vomiting, Hair loss, altered function of the liver are potential side effects of this treatment.
Risk of Infection as white blood cells are low and the patient to prone to get an infection. The infections could be bacterial, viral or fungal and will usually need antibiotics to control them.
Mucositis is due to the effect of chemotherapy on the inside lining of the mouth and digestive tract. This can limit the amount of food taken by the patient and other methods of feeding may be used in that instance.
Bleeding is a risk associated with this procedure due to low platelet count, but platelet transfusion can be given to keep the platelet counts up.
Graft versus host disease This is a reaction of the body to the transfused cells particularly if the stem cells or marrow is from a donor.