What is Lymphoma? How is Lymphatic Cancer Treated?

Lymphoma is a general term that describes cancers originating from the lymphatic system, which is part of the immune system. Lymphomas are commonly known as lymph node cancers, but the disease can also occur in organs without involving the lymph nodes.

What is Lymphatic Cancer, Lymphoma?

Lymphoma is a cancer of the lymphatic system. The lymphatic system is a network throughout the body that produces and stores white blood cells that fight infections. When lymphoma occurs, white blood cells multiply uncontrollably, leading to swelling in the lymph nodes. Lymphoma is generally divided into two types: Hodgkin lymphoma, which is more commonly seen in younger individuals, and non-Hodgkin lymphoma, which is more frequently seen in older individuals. Due to these differences, there are varying treatment approaches. Non-Hodgkin lymphoma is reported to be the fifth most common cancer type in the U.S. and the tenth most common in Turkey. One type seen in African countries is infectious, while the remaining types are mostly observed in organ transplant patients and individuals with diseases that weaken the immune system (e.g., AIDS). These groups represent a small fraction of all lymphoma patients. The cause of lymphoma is unknown for the vast majority of patients. Some types of lymphoma show fluctuating recovery periods; however, particularly aggressive types can lead to complications over time due to mass pressure or invasion of the bone marrow, where blood components are produced, by lymphoma cells.

Despite the many different subtypes of lymphoma, there are fundamentally two types:

• Hodgkin Lymphoma (Hodgkin Disease): This is one of the cancers that responds best to treatment. It is distinguished from other types of lymphoma by the presence of Reed-Sternberg cells.
• Non-Hodgkin Lymphoma (or all lymphomas other than Hodgkin lymphoma): According to the Leukemia & Lymphoma Society, approximately 601,180 people lived with lymphoma or achieved remission, a complete recovery, in 2009. About 148,460 of these individuals had Hodgkin lymphoma, while approximately 452,720 had non-Hodgkin lymphoma. It is estimated that 11.4% of all lymphoma diagnoses in 2009 were Hodgkin lymphoma cases.

HODGKIN LYMPHOMA

What are the risk factors?

Abnormal growth of cells in the lymphatic system can lead to spread to other organs. The disease is generally rare and occurs in adults aged 15-34 and those over 55. Each year, 3-4 new cases emerge per 100,000 people.

A documented history of infectious mononucleosis in young adults increases the risk of Hodgkin lymphoma threefold compared to the general population.
AIDS increases the likelihood of developing Hodgkin lymphoma.
Surgeries such as tonsillectomy and appendectomy increase the risk of Hodgkin lymphoma.
Familial clustering may be detected in some cases, similar to other types of cancer. The frequency of occurrence is high among siblings of patients with Hodgkin lymphoma.

What are the symptoms?

The most common finding in Hodgkin lymphoma is the presence of one or more enlarged lymph nodes. These nodes are usually painless and are most commonly found in the neck, upper chest, abdomen, or groin.

The most common symptoms include:

• Painless lumps: This is the most frequently observed symptom. These are swellings in the lymph nodes that are painless and typically larger than one centimeter in diameter. The lumps that are most likely to be noticed appear in the neck, armpits, or groin. These swellings do not cause pain or other symptoms but often increase in size over time. It should be noted that swelling of the lymph nodes is a very common condition, and a significant portion of individuals with swollen lymph nodes has diagnoses other than lymphoma. The most common cause of swollen lymph nodes is infection, and these swollen nodes usually shrink after the infection resolves.
• Fever of unknown origin: This is when body temperature exceeds 38ºC without any identifiable cause.
• Night sweats: The patient experiences severe night sweats that are enough to wet their clothing and sheets.
• Weight loss: This refers to losing more than 10% of body weight within six months.
• Persistent fatigue: This is a state of severe and ongoing weakness or fatigue.
• Cough and shortness of breath.
• Itching of the skin.

Is early diagnosis possible?

Worldwide, 62,000 people are diagnosed with Hodgkin disease each year; 58% (166,000) of the patients are male, and 42% (120,000) are female. Approximately 25,000 deaths occur globally each year due to this disease.

If the complaints mentioned above persist for more than two weeks, consult a physician.

How is the diagnosis made?

• Physical examination: All lymph nodes throughout the body should be thoroughly examined.
• Biopsy: Definitive diagnosis is made through histopathological examination. Therefore, in patients with lymph node enlargement, surgical removal of the lymph node and histopathological examination are necessary. If radiological examinations indicate the presence of enlarged lymph nodes in the thoracic or abdominal cavity in patients where lymph nodes are not palpable during physical examination, lymph node biopsy may need to be performed under general anesthesia.
• Bone marrow biopsy: Every patient diagnosed with lymphoma should also undergo a bone marrow biopsy to determine the stage of the disease. Assessing whether the disease has spread to the bone marrow is crucial for deciding on the appropriate treatment method.
• Imaging: This is usually a painless procedure that does not require anesthesia. Direct X-ray images, computed tomography (CT) scans of the neck, thorax, abdomen, and/or pelvis should be performed. Magnetic resonance imaging (MRI) should be planned if brain and spinal cord involvement is suspected. Lymphangiography, a rarely used method, provides a radiological evaluation of the lymphatic system. Gallium scanning is a imaging technique used in lymphoma, taking advantage of the accumulation of radioactive gallium in certain tumors.
• Blood count: Evaluation of the number and appearance of different blood cells, including red blood cells, white blood cells, and platelets, is necessary. An abnormality in these cells can sometimes be the first indication of lymphoma.
• Biochemical tests: These tests can provide information about whether the tumor has spread to the liver, kidneys, or other parts of the body.
• Central nervous system examination: Lymphoma can sometimes spread to the nervous system. When this occurs, abnormalities may be present in the cerebrospinal fluid found in the spinal cord and brain, and cancer cells may be detected in this fluid. To determine this, a physician may suggest a lumbar puncture, where fluid is collected from the lower back using a thin needle.
• Other tests: Echocardiography and some radionuclide tests may be necessary to assess heart and lung function.

What are the stages of the disease?

Hodgkin lymphoma consists of four clinical stages:

• Stage I: The disease is present in a single lymph node region.
• Stage II: The disease is present in multiple lymph nodes in either the thoracic or abdominal region.
• Stage III: The disease is present in lymph nodes in both the thoracic and abdominal regions.
• Stage IV: The disease is present in organs outside the lymph nodes, such as the liver, bone marrow, or lungs.

In staging, A, B, and E are important. The presence of systemic symptoms during diagnosis is classified as B, while their absence is classified as A. Systemic symptoms include fever, night sweats, and weight loss. The letter E is used when the disease has spread from a lymph node to an organ or when the disease involves a single organ outside the lymphatic system.

How is Hodgkin lymphoma treated?

In early stages, more than 90% of patients achieve complete recovery, while in advanced stages, this rate is between 60-80%. Therefore, definitive staging is performed first, and then Hodgkin lymphoma treatment is planned according to the disease stage. Following the staging process, treatment for early-stage Hodgkin lymphoma patients typically consists of 2-4 cycles of chemotherapy called ABVD, followed by radiation therapy to the affected area. For more advanced disease, treatment regimens with effective cancer drugs (such as ABVD and MOPP) should be administered in 6-8 cycles.

With appropriate treatment in early stages, the chance of complete recovery reaches up to 80%, and even in advanced stages, a lower percentage continues. Factors influencing treatment success in Hodgkin disease include the patient’s age, histopathological type of the disease, disease stage, and the presence of “B group” symptoms (systemic symptoms at the time of diagnosis). After 2-4 cycles of treatment, the status of the patients’ disease is assessed via PET scan, and in those with insufficient response or those who improve but later relapse, high-dose chemotherapy treatment using autologous stem cell transplantation is applied. If the patient does not recover, reduced-dose regimens for allogeneic stem cell transplantation from a suitable sibling may be planned. With these treatments, 50% of patients achieve recovery.

Radiotherapy: Treatment can be administered to limited areas or larger fields. Radiation is painless. Expected side effects of radiotherapy include fatigue, loss of appetite, throat irritation, nausea, cough, dry mouth, skin rashes, and hair loss.

Biological therapies: Biological therapies, including immunotherapy, utilize the body’s capacity to fight disease. Monoclonal antibodies are made against specific antigens. Cancer cells are eliminated using monoclonal antibodies created against certain antigens. Radioimmunotherapy allows for direct irradiation of the tumor by adding a radioactive molecule to monoclonal antibodies.

In interferon therapy, the effect of alpha interferon, a substance that occurs naturally in the body, in directly killing tumor cells is utilized.

Is it possible to prevent Hodgkin lymphoma?

The most effective behavior that can be recommended in this regard is for individuals to keep their immune systems strong through proper nutrition and adequate protection from infections. Individuals should undergo all recommended examinations and share them with their physicians if they suspect any conditions.

NON-HODGKIN LYMPHOMA (NHL)

What are the risk factors?

Non-Hodgkin lymphoma (NHL) refers to lymphomas that are not Hodgkin lymphoma and arise from lymphocytes. It has been reported that NHL occurs more frequently in individuals with congenital immune deficiencies or those whose immune systems are suppressed (such as in AIDS), as well as in those exposed to certain viral diseases (HTLV-1, EBV, HHV, HCV), medications (TNF-alpha inhibitors used in rheumatoid arthritis treatment, certain drugs used for epilepsy treatment, and chemotherapeutics used in cancer treatment), and certain occupations (such as those working in the paint industry, carpentry, leather industry, and roofing). It is known that herbicides and pesticides used in agriculture can lead to the development of NHL. Individuals living and working in areas with high concentrations of these substances in the soil and water are at risk.

While a direct link to diet cannot be established, it has been reported that individuals consuming a diet rich in animal fats and red meat have a higher incidence of NHL compared to those who consume a diet predominantly consisting of vegetables and fruits. The ratio is lower in those who consume more vegetables, particularly fiber-rich vegetables, compared to those who consume fruit.

What are the symptoms?

The most common symptoms of NHL include:

• Painless lumps in the neck, armpit, or groin,
• Unexplained weight loss,
• Fever,
• Excessive night sweats,
• Cough, breathing difficulties, or chest pain,
• Persistent fatigue and weakness,
• Abdominal pain, swelling, or a feeling of fullness.

The above symptoms are not solely indicative of cancer; they can also develop in infections or other health issues. Therefore, it is advisable for individuals experiencing these symptoms for more than two weeks to see a physician.

Is early diagnosis possible?

Early diagnosis is possible if the patient notices the above complaints and seeks medical attention. If the complaints mentioned above persist for more than two weeks, it is advisable to consult a doctor.

Every year, approximately 286,000 people worldwide are diagnosed with Non-Hodgkin lymphoma; 60% of the patients (38,000) are male, and 40% (24,000) are female. An average of 161,000 deaths occur globally each year due to this disease.

How is the diagnosis made?

The diagnostic procedures to determine whether the patients' complaints are consistent with NHL are outlined below:

• Physical examination: A comprehensive medical history is taken, and a physical examination is performed for patients presenting with the aforementioned complaints.
• Blood tests: In addition to a complete blood count, levels of other cells and/or substances (e.g., lactate dehydrogenase [LDH]) in the blood are investigated.
• Radiological examinations: Chest X-rays are performed to check for the presence of swollen lymph nodes in the chest cavity.
• Biopsy: To confirm the diagnosis and plan treatment, samples are taken from accessible swollen lymph nodes and sent for pathological evaluation.

What are the stages of the disease?

The staging of the disease is done according to the Ann Arbor staging system. According to this system:

• Stage I: The disease is present in a single lymph node region.
• Stage II: The disease is present in lymph nodes in multiple areas in either the chest or abdominal region.
• Stage III: The disease is present in lymph nodes in both the chest and abdominal regions.
• Stage IV: The disease is present in organs outside of the lymph nodes, such as the liver, bone marrow, or lungs.

How is it treated?

In the initial step of planning treatment for NHL, certain information must be obtained. This includes the type of NHL at the cellular level (e.g., follicular lymphoma), stage, disease progression rate, the patient’s age, and any additional health issues. There are slow, fast, and very fast progressing types of Non-Hodgkin lymphoma. Treatment options vary depending on whether the disease is slow or fast progressing. In slow-progressing lymphoma, radiotherapy or chemotherapy is administered in the early stage, whereas no treatment is given if the patient has no complaints in the advanced stage. This is because patients can live for a long time, and treatment does not extend their lifespan.

Despite obtaining a response to chemotherapy in NHL patients, recurrence of the disease (relapse) occurs at varying rates depending on the subtype of lymphoma after treatment. When patients who have completed treatment and are being monitored without medication begin to experience excessive swelling of the lymph nodes, weight loss, fever, and sweating, suspicion of the disease returning should arise. After 2-4 cycles of treatment, the condition of the patients is evaluated; in those with insufficient response or those who improve with treatment but later relapse, high-dose chemotherapy treatment is performed using autologous stem cell transplantation. If there is still no improvement, reduced-dose regimen allogeneic stem cell transplantation from a matched sibling may be planned. For certain types of lymphoma (like mantle cell lymphoma) or advanced-stage T-cell lymphoma, autologous stem cell transplantation is planned following initial chemotherapy.

• Radiotherapy: This is given after chemotherapy for patients with early-stage disease or those with significantly enlarged lymph nodes in advanced stages. Special machines that produce external radiation are used for this purpose.
• Immunotherapy: In recent years, drugs that recognize and kill lymphoma cells have been developed. In some patients, interferon-alpha is used to try to extend the duration of remission (the disease-free period).
• Stem cell transplantation: Autologous stem cell transplantation is performed in suitable patients with NHL. Allogeneic stem cell transplantation from another donor is rarely performed. In patients under 60-65 years old with relapsed disease after chemotherapy or those who do not respond to initial treatment, transplantation of stem cells prepared from their own bone marrow (autologous stem cell transplantation) should be performed.

Is it possible to prevent lymphoma?

The most effective behavior that can be recommended in this regard is for individuals to strengthen their immune systems through proper nutrition and adequate protection against infections. In cases where individuals are suspected by their doctor, they should undergo all recommended examinations and share the results with their physician.

Is there a place for non-drug alternative therapies in lymphoma?

Alternative treatments such as nettle, pollen, herbal teas (boiled and consumed as a beverage), parsley juice, etc., in patients with lymphoma can cause significant side effects and may render standard chemotherapy ineffective, leading to an increased tendency for infections. These treatments are not recommended.

Targeted therapy in lymphoma

Targeted therapies are particularly promising in lymphoma treatment. The diversity of these treatments is rapidly increasing as genetic characteristics related to lymphoma cells are understood through advanced diagnostic methods. Prof. Dr. Serdar Turhal, a Medical Oncology Specialist at Anadolu Health Center, emphasizes that the chance of success in lymphoma treatment depends on the type of cell; in well-behaving Hodgkin lymphoma, success rates exceed 90%, while in some aggressive non-Hodgkin lymphomas, it may be below 30%. However, he notes that targeted therapy could increase these rates.