Non-Hodgkin's lymphoma treatment

Non-Hodgkin Lymphoma Treatment

Non-Hodgkin's lymphoma is the most common type of lymphoma, and it appears in many types, most of which are outside the lymphatic system, and its diagnosis and treatment requires the best and most skilled hands of Turkish doctors.

What is lymphoma?

The concept of lymphoma is derived from the cells affected by the disease, which are lymphocytes (a type of white blood cell), especially type B lymphocytes (therefore, they are classified as blood cancers), where the section lymph refers to lymphocytes and suffix oma means tumor, that is, lymphocyte tumor.
Lymphomas usually develop when a change or mutation occurs within lymphocytes, causing the abnormal (neoplastic) cell to multiply faster than normal lymphocytes or to live longer and not undergo programmed cell death (Apoptosis).
Cancerous lymphocytes can travel through the blood and lymph system and spread and grow in many parts of the body, including the lymph nodes, spleen, bone marrow and many other organs.
 
Lymphomas are divided into two main categories:
Hodgkin's lymphoma (It was called Hodgkin's disease):  It includes certain cell types characteristic of this disease (we will mention them later).
Non-Hodgkin lymphoma: It is the most common, and includes all tumors that do not fall under the classification of Hodgkin lymphoma.
Each type spreads, divides and responds to treatment differently, so it is necessary to know which type the patient has to choose the optimal treatment plan, whether for Hodgkin's tumors or non-Hodgkin's tumors.

Overview of the lymphatic system and lymphocytes

Before we talk about the pathological or cancerous state of the cells and the lymphatic system, we will mention an overview of the normal physiological state of the lymphatic system and lymphocytes.

The lymphatic system is an important part of the immune system in the human body and it rids the body of many toxins and eliminates many pathogens that attack the body.
The lymphatic system consists of the lymph, lymph vessels, lymph nodes, bone marrow, spleen, thymus gland, and tonsils.

Picture of the lymphatic system in the human body and a section of the lymph node
Overview of the lymphatic system to facilitate understanding of non-Hodgkin's lymphoma
 
 B and T lymphocytes arise from the bone marrow (which is a primary lymphoid organ) and are initially precursors and then develop into mature lymphocytes in the same bone marrow for type B, while T cells develop in thymus.
The mature B cells then migrate to the lymph nodes (secondary lymphoid organs) where they gather as follicles in the lymph node cortex.
Mature T cells congregate in the paracortex.
 
On the surface of B lymphocytes, there are protein complexes called CD (cluster of differentiation) with different numbers that act as markers that identify the body's cells and help your body distinguish different types of cells.
B cells in the normal state express CD20 and CD45.
 
In the event that an antigen binds to the surface of the B cell, this cell activates, and some of it develops into plasma cells that secrete IgM, which are usually found in the middle of the lymph nodes in the so-called medulla, and some of them travel to the center of the lymphatic follicle and develop into a centroblast. The centroblast then divides and multiplies and forms what's called the germ center, where a rearrangement occurs in the immunoglobulin genes of these cells and they develop into centrocytes, some of which secrete IgA and others IgG.
 
The centrocytes then differentiate into either plasma cells or memory cells, and the latter circulates in the blood, where part of it remains, or settles in the spleen or in the mucosa-associated lymphoid tissue known as MALT.
While the development and differentiation of T lymphocytes begins in the thymic gland.
Mature cells express either CD4, in this case, helper T cells, or CD8, called killer or suppressor T cells.

Non-Hodgkin's Lymphoma

Non-Hodgkin's lymphoma is a type of hematological neoplasm that specifically affects lymphocytes, and is sometimes abbreviated and called NHL.
It is the other more common type of lymphoma, as it is the seventh most common cancer affecting adults around the world.
The incidence of this cancer is estimated at about 72,000 cases annually, with the number expected to increase significantly in upcoming years.
 
Non-Hodgkin's Lymphoma is not a single disease as some think, but rather a group of diseases that affect lymphocytes, as it has been estimated that there are more than 86 types of Non-Hodgkin's Lymphoma.

How do doctors distinguish Hodgkin's lymphoma from non-Hodgkin's lymphoma?

It can be distinguished by the location of the tumor and its accompanying symptoms, but the main difference on which the diagnosis is based is the microscopic characteristics, where in Hodgkin's lymphoma there are tumor cells called Reed-Sternberg cells with a distinctive appearance, As they look like an owl's eye.
Also what helps distinguishing between the two types is that Hodgkin's Lymphoma arises mostly in the lymph nodes and is rarely seen outside these nodes, unlike non-Hodgkin's lymphoma, which is often seen outside the lymphatic system.
 
In Non-Hodgkin's Lymphoma, there is a change or mutation (for several reasons we will mention later) in the genes of lymphocytes, where these cells become not subject to programmed cell death and divide randomly, and the immune system cannot control the division of these cells, giving these random divisions Nonfunctional tumor cells.
These cells can grow in any organ of the body and symptoms vary depending on the affected organ.

Types of Non-Hodgkin's Lymphoma

As we mentioned, Non-Hodgkin's lymphoma has many types (more than 86 types), but to make understanding and classification of the disease easier, Non-Hodgkin's lymphoma cancer types have been classified in two main categories:

B-cell lymphoma

This lymphoma constitutes about 85% of non-Hodgkin's lymphoma cases, and it is either slow-growing indolent or fast-growing aggressive and includes different types, including:

Diffuse Large B Cell Lymphoma

It is the most common type of lymphoma from B-cell lymphomas, and it accounts for approximately 22% of them, and it is diagnosed in one out of every three cases with Non-Hodgkin's lymphoma.
It is characterized by being rapidly growing, and it affects the elderly more, especially those in their sixties, and usually appears as a mass in the abdomen, chest, or lymph nodes and gives metastases to multiple sites such as the liver, digestive tract, and even the brain, spinal cord and thyroid gland.
Symptoms are usually B symptoms (will be mentioned later in the Symptoms and Signs section), and may be asymptomatic at first.
 
It is highly responsive to treatment and treatable despite its rapid growth and it is usually associated with metastases.
There are many types of Diffuse Large B cell Lymphoma, and we mention only one of them due to its importance, which is Primary mediastinal diffuse B lymphoma It often appears in young women behind the sternum and can cause respiratory symptoms due to pressure on adjacent structures, or even cause swelling of the face and neck when it compresses the superior vena cava.

Follicular lymphoma

It is the most common indolent lymphoma, with 1 in 5 patients diagnosed with Non-Hodgkin's lymphoma, and the average age of infection is in the sixties.
The tumor arises in the lymph nodes and bone marrow, and this type of lymphoma is a chronic disease that is often incurable, as patients live for many years despite having this lymphoma.
This lymphoma can develop into diffuse large B-cell lymphoma.

Chronic lymphocytic leukemia/Small lymphocytic lymphoma (CLL/SLL)

They are almost the same disease, as they arise at the expense of small lymphocytes, but the difference is in the location of the tumor, where CLL arises in the blood and bone marrow, while SLL arises in the lymph nodes and spleen.
Treating them is difficult, but the patient often lives for long periods of time.

Burkitt Lymphoma

It is a rare, fast-growing (aggressive) type of non-Hodgkin's lymphoma, named after the doctor who first described it in children in sub-Saharan Africa.
It has three sub-types:
  • Endemic Burkitt: As we mentioned, it is spread in children and adolescents in Africa and is often associated with infection with the Epstein-Barr virus, and it often affects their jaw and facial bones, and it can also arise in the intestines, kidneys and other organs.
Photo of an African boy with Burkitt lymphoma in the jaw
Picture showing endemic Burkitt's lymphoma, which is widespread in Africa in enfants and young people and can cause serious facial disfigurements
  • Isolated Sporadic Burkitt: They are isolated cases that appear in different parts of the world, and in this case they often arise in the abdomen.
  • Immunodeficiency-associated Burkitt: It is associated with acquired immunodeficiency syndrome (AIDS).
  • Burkitt's lymphoma under the microscope looks like a starry sky at night, due to the presence of Tingible bodies, which are large macrophages that have ingested the tumor cells.

    It needs immediate and intensive treatment due to its rapid spread and growth, although half of the patients recover after intensive chemotherapy.

    We note the characteristic microscopic appearance of Burkitt's lymphoma and the presence of Tingible bodies (white spots)
    We note the characteristic microscopic appearance of Burkitt's lymphoma and the presence of Tingible bodies (white spots), which are large macrophages that have ingested the neoplastic cells.

    Mantle Cell Lymphoma

    It is a rare type of non-Hodgkin's lymphoma, arises in the mantle zone of the lymph nodes, and is often fast growing (can be indolent).
    Often this lymphoma is not diagnosed until late stages and is often difficult to treat and cure.
    There is an increase in the synthesis of the protein Cyclin D, which makes it easy to diagnose this lymphoma with a biopsy.

    Marginal Zone Lymphoma MZL

    It is slow growing and often appears after the age of sixty and is divided into three sub-types:
    • Extra-Nodal MZL: the most common, It arises in areas outside the lymph nodes, often in MALT, where this type can be called MALT lymphoma, and it is either gastric or Intestinal, this type appears with a medical history of chronic infection (mostly with H.Pylori).
    • Nodal MZL: it arises in the lymph nodes or bone marrow.
    • Splenic MZL: it arises in the spleen, blood, or bone marrow.

    Lymphoplasmacytic Non-Hodgkin's Lymphoma

    It usually arises in the bone marrow, lymph nodes, and spleen.
    It is characterized by the secretion of immunoglobulins by tumor cells called immunoglobulins M, which accumulate in the blood at high levels. This accumulation leads to an increase in the thickness and viscosity of the blood, and this case is calledWaldenstrom Macroglobulinemia.

    T cell non-Hodgkin's lymphoma

    They account for approximately 7% of non-Hodgkin's lymphoma cases and have many types, but they are rare.
    To make it easier, it is divided into two parts, depending on the degree of differentiation of the T cells from which the tumor arises:

    T-lymphocytic leukemia

    It is rare and arises at the expense of T cells in its initial stages, and it first arises in the thymus gland and grows to large sizes that can affect breathing and cause swelling in the face and neck.
    The disease is rapidly spreading and growing, but responds well to chemotherapy and is curable if detected early.

    Peripheral T-cell lymphoma

    They arise at the expense of more mature T cells, a general term that includes many subtypes depending on where the tumor originates, and we will mention them briefly:
    • Anaplastic Large Cell Lymphoma: ALCL can be systemic (occurring all over the body) or cutaneous (limited to the skin). Systemic ALCL is usually at an advanced stage when diagnosed and is fast-growing.
      The systemic type is further categorized into two types based on ALK (Anaplastic Lymphoma Kinase) positivity or negativity. Systemic ALCL responds well to treatment, especially ALK-positive disease, but ALK-negative patients may require more aggressive treatments, and relapse occurs more frequently than ALK-positive disease. .
    • Angioimmunoblastic T-cell lymphoma: It is a rare, severe type that accounts for about seven percent of all patients with T-cell lymphoma in the United States.
      Most patients are middle-aged to elderly and are diagnosed at an advanced stage, and there is some evidence that AITL develops from a persistent immune response possibly due to an underlying viral infection (eg Epstein-Barr virus).
      Initial symptoms often include fever, night sweats, rash, itching, some autoimmune disorders such as autoimmune hemolytic anemia and immune thrombocytopenia and with elevated levels of gamma globulin in the blood.
    • Cutaneous T-cell Lymphoma: It is a general term that includes several under slow-growing types, most of which are specific to the skin, and one of these types is Mycosis Fungoides, which is the most common type and is characterized by the presence of papules, plaques, and itchy skin lesions on the course of the body. Another type is Sézary syndrome, a syndrome that affects the blood and skin and appears with red skin. Severely itchy in most parts of the body and tumor T cells called Sézary cells can be seen.
    • Lymphoblastic lymphoma: It is rare and arises from lymphoblasts and is more common on the expense of T-cell lymphoblasts.
     
    There are many other types, but they are not mentioned due to the lack of their clinical importance.

    Causes and risk factors for non-Hodgkin lymphoma

    The cause of non-Hodgkin's lymphoma has not yet been clearly established.
    As we mentioned earlier, the mechanism of cancer formation through different genetic mutations in the genes of lymphocytes is agreed upon, but no real and clear reason for the emergence of these mutations has been discovered.
    There are some risk factors that often have a role in the emergence of these mutations in non-Hodgkin's lymphoma patients, including:
    • Age: The older the patient, the higher the incidence of Non-Hodgkin's lymphoma, as more than a third of cases were diagnosed in the elderly over 75 years.
    • Gender: Where there is a slight tendency for lymphoma to occur in males more than in females.
    • Race: It is believed that white people have a tendency to develop non-Hodgkin lymphoma more than people with black skin, but this belief needs more detailed studies.
    • Family History: The incidence of Non-Hodgkin's lymphoma increases when there is a case among first-degree relatives (brother, father, son...).
    • Obesity Recent studies have shown that obese people have an increased risk of some types of Hodgkin lymphoma.
    • Hereditary Immune diseases: Such as hypogammaglobulinemia or Wiscott-Aldrich syndrome.
    • History of previous exposure to radiation: Such as those who underwent previous radiotherapy or, rarely, survivors of nuclear and chemical disasters.
    • Autoimmune diseases: Such as rheumatic fever, Sjögren's disease, systemic lupus erythematosus (SLE) or celiac disease have all been linked to non-Hodgkin's lymphoma, and AIDS, caused by HIV, may also have a role in this cancer.
    • EBV and Human T-lymphotrophic Virus type I: It has been proven that they have a significant role in the occurrence of genetic mutations in patients with non-Hodgkin lymphoma.
    • Chronic infections: Such as infection caused by H. pylori, hepatitis virus and Chlamydia psittaci.

    Symptoms and Signs

    Symptoms and signs of non-Hodgkin lymphoma vary greatly, due to the presence of many types and the possibility of cancer arising in almost any organ of the body.
    Lymphoma may not have any symptoms until the tumor has grown to a certain size.
    The most common presentation in patients with non-Hodgkin's lymphoma is Painless swelling of the lymph nodes Especially in the cervical, axillary and groin lymph nodes.
    Other symptoms include:
    • Profuse night sweats
    • Unexplained weight loss
    • Rashes or lumps with itchy skin all over the body
    • Unexplained fever
    • Constant feeling of tiredness and fatigue
    • Increased possibility of bleeding, such as nosebleeds and heavy menstruation
    • Breathlessness
    • Feeling full after eating a small amount of food
    • Frequent infections
    Symptoms (night sweats, weight loss, fever) are called B symptoms.
    The appearance of some other symptoms of lymphoma depends on the place of metastases from non-Hodgkin's lymphoma. The symptoms are often mechanical. Intestinal obstruction occurs if there is metastases to the digestive system, or a lack of blood cell formation occurs in the case of bone metastases. It may also cause compression of the spinal cord if there is a metastasis next to it.

    Diagnosis of Non-Hodgkin's Lymphoma in Turkey

    The Diagnostic and investigative methods has evolved significantly in Turkey, especially in the field of oncology.
    Non-Hodgkin's lymphoma patients often present with an enlarged lymph node history and sometimes some other symptoms, but the lymph nodes enlarge for other reasons that are more common than Non-Hodgkin's Lymphoma and the most common cause of Lymph nodes swelling is Infection.
     
    Diagnosis depends mainly on the doctor's skill and experience, and many costly procedures can be dispensed with if the diagnosis is directed in the right direction.
    First, the clinical history must be taken in detail, and then a clinical examination of the patient is conducted, and then the doctor proceeds to other, more specific procedures.
    To help diagnose Non-Hodgkin's Lymphoma, the following may be done:
    • Medical-Based Imaging: Such as ultrasound, CT, positron emission tomography (PET-Scan), simple chest radiograph, and magnetic resonance imaging (MRI).
    • Blood tests: Such as a complete blood count (CBC), and blood chemical tests, as well as titration of certain enzymes in case of suspicion of a particular type of non-Hodgkin's lymphoma.
    • Bone Scan.
    • biopsy: It is the most important and most accurate diagnostic method, but it is not requested until after other causes and their types are denied, and it includes bone marrow biopsy.

    If you have any problem or question then Bimaristan medical center will answer all your questions, feel free tocontact us,Bimaristan center is your family in Turkey.

    Classification of non-Hodgkin's lymphoma

    The same classification in Hodgkin's Lymphoma is used here, and it's called Lugano classification.

    Classification of non-Hodgkin's lymphoma (Lugano classification)
    The staging of non-Hodgkin's lymphoma (Lugano's classification) depends on the number and location of affected nodes as well as near and far metastases.

    Non-Hodgkin's Lymphoma Treatment in Turkey

    Choosing Non-Hodgkin's lymphoma treatment depends on several factors, including the patient's age and the type and stage of non-Hodgkin's lymphoma.

    It is not always necessary to resort to treatment if non-Hodgkin's lymphoma is diagnosed, as it can be monitored if there are no symptoms or the patient's life is not affected.
    Among the most common treatments in Turkey:

    Chemotherapy for non-Hodgkin's lymphoma

    It is the most common treatment for non-Hodgkin's lymphoma, and Chemotherapy in Turkey has evolved significantly until it became one of the leading countries in the field of chemotherapy.
    Chemo drugs target any cell that is constantly dividing in the body, including cancer cells, and as a result, they have many side effects. Cancer cells are not the only cells that renew quickly and constantly in the body (hair cells, skin, blood cells… are also constantly renewed).
    Treatment is usually given in the form of drug combinations between several drugs to get a better result and includes many combinations of drugs used in Chemotherapy for non-Hodgkin's lymphoma include the monoclonal antibody rituximab (Rituxan), which is usually abbreviated with the letter R and placed at the beginning or end of the abbreviation for a co-administration, such as R-CHOP or CHOP-R consisting of cyclophosphamide, doxorubicin, vincristine, prednisone.

    Intrathecal (into the spinal canal or subarachnoid space) chemotherapy may also be used to treat primary lymphomas that originate in the testicles or sinuses, diffuse large B-cell lymphoma, Burkitt's lymphoma, lymphoblastic lymphoma or some Aggressive (rapidly growing) T-cell lymphomas, given to reduce the spread of lymphoma cells to the brain and spinal cord.

    Intrathecal injection of chemotherapy drugs into the spinal canal or subarachnoid space (the Ommaya Reservoir is the area where the cerebrospinal fluid drains).
     Intrathecal injection of chemotherapy drugs into the spinal canal or subarachnoid space (the Ommaya Reservoir is the area where the cerebrospinal fluid drains).

    Immune lymphoma treatment protocol

    The field of Immunotherapy in Turkey has expanded significantly in recent times and new generations of drugs and synthetic molecules have appeared to reduce collateral damage, and Studies on Immunotherapy methods are still being developed and conducted.
    Immunotherapy is based mainly on strengthening the human body's natural immunity or using synthetic antibodies to eliminate deformed cancerous cells. The most common of these methods are:

    Monoclonal antibodies

    They are synthetic proteins that attack cells with certain markers, which greatly reduces side effects, including:

    • Antibodies that target the CD20 antigen: CD20 is a protein found on the surface of B cells. These drugs include rituximab (Rituxan), obinutuzumab (Gaziva), ofatumab (Azera) and ibritumumab tuxitan (Zevalin).
    • Antibodies targeting the CD30 antigen: It is a protein found on the surface of T cells. An example of this drug is brentuximab vedotin (Adcetris).
    • Antibodies targeting CD52 antigen: It is a protein found on the surface of T cells, and a drug that targets this antigen is alemtuzumab.

    There are many other drugs, but they are not mentioned here for lack of usage.

    Chimeric Antigen Receptor (CAR) T cells

    This method is considered a quantum leap in the treatment of Non-Hodgkin's lymphoma and Studies is still ongoing about this method.
    In this method, T cells are taken from a person's blood and modified in the laboratory to have specific receptors on their surface. These chimeric receptors can attach to proteins on the surface of cancerous lymphoma cells, and this binding enables the T cells to destroy tumor cells.

    ADC Antibody-Drug Conjugate

    It is a monoclonal antibody loaded with a chemical drug, and after the monoclonal antibody binds with the cancer cell, it releases the chemical drug that works to kill and disrupt the tumor cell by a certain mechanism.

    Approved antibody conjugates and drugs include:

    • Brentuximab Vedotin (Adcetris)
    • Loncastuximab Tesirine-lpyl (ZYNLONTA)

    Targeted non-Hodgkin's lymphoma treatment

    Targeted therapy is a type of specialized treatment that targets the proteins that control how cancer cells grow, divide, and spread, somewhat similar to immunotherapy. New studies emphasize the importance of this treatment in the treatment of non-Hodgkin's lymphoma, and some of the types of this treatment are:

    • Biosimilars: They are similar to biological medicines.
    • Bruton Tyrosine Kinase Inhibitors: Bruton Tyrosine Kinase is an enzyme necessary for the growth of neoplastic cells.
    • PI3K Inhibitors: PI3K is a signaling molecule that helps B cells grow, move, divide, and survive, so PI3K inhibitors help stop or slow the growth of cancerous lymphoma cells.
    • DNA Methyltransferase Inhibitors: Methylation enzymes have a significant impact on gene regulation and are a potential prognostic biomarker for genetic disorders and diseases. Inhibition of these enzymes helps stop cellular growth and activate programmed cell death.

    Radiotherapy for non-Hodgkin lymphoma

    Radiation therapy is a treatment that uses high-energy x-rays to destroy tumor cells and reduce the size of the local tumor, as it can be used in the treatment of some types of localized lymphoma or in the irradiation of some large tumors that have affected nearby organs.

    The field of radiotherapy andInterventional radiotherapy has witnessed a quantum leap in Turkey, due to its importance in the treatment protocol for many common cancers around the world.

    Treatment of non-Hodgkin's lymphoma with stem cell and bone marrow transplantation

    Stem cell transplantation (injection) is a treatment used to replace the lack of cellular hematopoietic precursor cells after undergoing other therapies, especially high-dose intensive chemotherapy, as these treatments deplete hematopoietic cells and can enter the patient's body into catastrophic disorders.

    This process takes place in two ways:

    • Implantation of stem cells from the same person: In this method, we take healthy stem cells before undergoing other treatments (because they are depleted after treatment), and this type has two methods that can be followed depending on the place from which these cells were taken. In the first type, stem cells are taken from the blood, which is the most common and widely used method due to the ease of obtaining these cells and their abundance. In the other method, cells are taken from bone marrowthen the treatment is called bone marrow transplant
    • Transplanting stem cells from another person: It is often a relative of the patient as a brother or sister, and it can also be a stranger after the necessary cell-matching tests.

    And because of the many treatments and their combinations, you can consult contact us Bimaristan Medical Center will help you choose the best treatment with the best experienced hands in Turkey.

    Non-Hodgkin's Lymphoma Cancer Awareness Month

    An estimated 81,560 people in the United States will be diagnosed with non-Hodgkin's lymphoma in 2023, according to the National Cancer Institute.
    Hodgkin's and non-Hodgkin's lymphomas can occur in children, adults, and at any age.
    September is Leukemia and Lymphoma Awareness Month as it spreads awareness campaigns and urges people to get regular checkups, and shows that the disease is treatable.

    Sources:

    1. Lymphoma.org
    2. Cancer.gov
    3. NHS.UK
    4. LLS.org
    5. Cancer.org
    6. leukaemia.org

    Frequently Asked Questions:

    The two types can be distinguished somewhat by symptoms and the location of the swelling and pain, but the real difference remains dependent on the microscopic arena and the presence or absence of Hodgkin's cells or Reed-Sternberg cells.

    Chemotherapy is currently the best option as a first-line treatment, which can be combined with other treatments such as radiation and immunotherapy or targeted therapies.

    Monoclonal antibodies are synthetic proteins designed to attack cells with specific markers or antigens on their surface, and they are more targeted than chemotherapy, which targets all the constantly regenerating cells in the body.

    Diagnosis remains dependent on the doctor's experience and skill, and the clinical history and radiological or laboratory investigations may not be specific enough to diagnose non-Hodgkin's lymphoma, but the biopsy remains the best and most qualitative test for lymphoma in general.

    The five-year survival rate varies widely with the type and grade of lymphoma, but is often between 71-77 percent overall.

    If you are planning for treatment in Turkey
    you can talk to us here.

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