Diffuse Large B-Cell Lymphoma
Diffuse large B-cell lymphoma (DLBCL) is a fast-growing blood cancer that affects your lymphatic system. Healthcare providers typically treat it with a combination of cancer drugs. The combined drugs
What is diffuse large B-cell lymphoma?
Diffuse large B-cell lymphoma, or DLBCL, is a blood cancer that involves changes in your B cells, a particular type of white blood cell (lymphocyte). It’s the most common form of aggressive non-Hodgkin lymphoma and a type of B-cell lymphoma.
DLBCL affects your lymphatic system. Your lymphatic system is a network of tissues, vessels, and organs that help fight infection in your body. Normal B cells are a part of that infection-fighting network. But with DLBCL, healthy B cells change into fast-growing cancer cells that overtake healthy ones. They’re no longer able to fight off infection-causing invaders, like viruses and bacteria.
With diffuse large B-cell lymphoma, cancerous B cells may appear in your lymph nodes. But they may also appear in virtually any organ, including your gastrointestinal tract, thyroid, skin, breast, bone, or brain.
Although it’s aggressive, DLBCL is often treatable and curable, especially with early diagnosis and treatment.
Types of DLBCL
The World Health Organization (WHO) has identified over a dozen different types of DLBCL. Each type’s unique traits tell healthcare providers how the cancer will likely progress and respond to treatment. The classifications depend on things like:
Genetic changes. The genetic changes in the lymphoma cells are the most important identifier.
The part of your body where DLBCL starts. For example, primary CNS lymphoma starts in your central nervous system (CNS). Primary mediastinal B-cell lymphoma starts in the center of your chest (mediastinum).
If there’s an association with a virus. Some types of DLBCL happen in people with a specific virus. For example, people with EBV-positive DLBCL have an Epstein-Barr virus infection.
Diffuse large B-cell lymphoma is a heterogeneous group of lymphomas. This means that the different subtypes have different genetic features, behaviors and responses to treatment. The subtypes depend on where the cancer is in the body, which genes and proteins are involved, and whether the cancer involves a virus such as Epstein-Barr virus (EBV). The subtypes of diffuse large B-cell lymphoma include:
Diffuse large B-cell lymphoma, not otherwise specified.
T-cell-histiocyte-rich large B-cell lymphoma.
Anaplastic lymphoma kinase (ALK) positive large B-cell lymphoma.
Large B-cell lymphoma with IRF4 rearrangement.
EBV-positive diffuse large B-cell lymphoma.
Diffuse large B-cell lymphoma is associated with chronic inflammation.
Fibrin-associated large B-cell lymphoma.
Fluid overload-associated large B-cell lymphoma.
Primary large B-cell lymphoma of immune-privileged sites.
Primary cutaneous diffuse large B-cell lymphoma, leg type.
Primary diffuse large B-cell lymphoma of the central nervous system.
Intravascular large B-cell lymphoma.
Understanding how the specific type of diffuse large B-cell lymphoma will impact your care journey is important, but the specifics can be confusing. Ask your provider to explain how your type of DLBCL will impact treatment options and outlook.
How common is diffuse large B-cell lymphoma?
Diffuse large B-cell lymphoma is the most common type of lymphoma. But as cancer diagnoses go, it’s still uncommon overall. According to the National Cancer Institute, in 2020, about 6 people in 100,000 received a DLBCL diagnosis. In comparison, about 500 people in 100,000 received a diagnosis of cancer affecting any part of their bodies.
Symptoms and Causes
What are the symptoms of DLBCL?
The symptoms most people notice with diffuse large B-cell lymphoma are swollen lymph nodes in their neck, armpits or groin. They usually appear as a lump that doesn’t go away and seems to be getting larger. The lump isn’t usually painful, but it can be.
About 30%of people with DLBCL have “B symptoms,” which include:
A fever above 103 degrees Fahrenheit (39.5 degrees Celsius) that lasts longer than two days or comes and goes
Unexplained weight loss that involves losing more than 10% of your body weight over six months
Heavy night sweats (so intense that they drench your sheets)
Having these symptoms doesn’t necessarily mean you have diffuse large B-cell lymphoma. That said, you should contact a healthcare provider anytime you notice changes in your body that last for several weeks.
Diffuse large B-cell lymphoma symptoms can vary depending on where the lymphoma develops.
The most common signs and symptoms include:
A fast-growing mass in the neck or belly.
Painless swelling in the neck, armpit, or groin.
Fever.
Fatigue.
Drenching night sweats.
Losing weight without trying.
If DLBCL is in the gastrointestinal system, symptoms may include:
Pain or fullness in the belly.
Nausea.
Vomiting.
Loss of appetite.
Losing weight without trying.
DLBCL of the nervous system can affect the brain, cranial nerves, spinal cord and the protective coatings on the brain and spinal cord, called the meninges. It also may affect the eyes.
When the nervous system is involved, symptoms may include:
Headaches.
Confusion.
Vision changes.
Troubles with thinking and speaking.
Changes in behavior.
Seizures.
DLBCL can affect other parts of the body and cause symptoms such as:
In the chest, cough, shortness of breath, trouble swallowing, and pain when breathing.
In the bones, bone pain with a risk of fracture.
In the liver, belly pain.
In the kidneys, blood in the urine, increased urination, frequently waking up to urinate, and belly or lower back pain.
In the skin, skin changes and a rash on the legs.
What causes diffuse large B-cell lymphoma?
Diffuse large B-cell lymphoma happens when B cells mutate (change). These are acquired genetic mutations, meaning you develop them during your lifetime instead of being born with them.
Risk factors
Medical researchers aren’t sure what triggers the mutations in DLBCL, but they’ve identified several factors that may increase your risk. Risk factors for diffuse large B-cell lymphoma include:
Age. Most people diagnosed with DLBCL are in their 60s. The average age of diagnosis is 64 years.
Sex. DLBCL is slightly more common in males.
Race. DLBCL affects more people who are white than people who are Black.
Family history of DLBCL. The genetic mutations in DLBCL aren’t hereditary, which means they don’t run in families. Still, studies show you’re at a slightly higher risk if a first-degree biological relative (parent, sibling, or child) also has DLBCL. Medical researchers aren’t sure why.
Infections. Viral infections associated with DLBCL include Epstein-Barr virus, human immunodeficiency virus (HIV), and hepatitis B and C.
Weakened immune system. Having a condition that impacts your immune system is the most significant risk factor for DLBCL. Examples include having a primary immunodeficiency or autoimmune disorder, or taking immunosuppressants after an organ transplant.
Increased body mass index (BMI) in young adults. The risk is especially high for young adults with obesity that persists throughout adulthood.
Exposure to toxic substances. Exposure to pesticides used in farming and certain chemicals used in manufacturing may increase your risk.
Diagnosis and Tests
How is diffuse large B-cell lymphoma diagnosed?
Healthcare providers diagnose DLBCL with a lymph node biopsy. This procedure removes all or part of a lymph node to check it for cancer cells. They also do genetic testing to learn which cell mutations are involved.
If you do have DLBCL, your provider may order additional tests to learn more about it, including whether it’s spread beyond your primary lymph node. Tests include:
Blood tests. These include a complete blood count (CBC) to check your general health and tests that detect viruses, like HIV, EBV, and hepatitis B and C.
Lactate dehydrogenase (LDH) test. This test checks the level of LDH (an enzyme) in your body fluid. Over 50% of people with DLBCL have high levels.
Imaging tests. You may need a CT scan, an MRI, or a PET scan to show whether the cancer has spread throughout your body.
Bone marrow biopsy. This test checks for lymphoma cells in your bone marrow.
Lumbar puncture. This test checks for lymphoma cells in the fluid surrounding your spinal cord.
Stages of diffuse large B-cell lymphoma
Healthcare providers use cancer staging systems to determine how advanced the cancer is. This helps them develop treatment plans and estimate prognosis, or expected outcome. The stages of DLBCL are:
Stage I: The cancer is in one lymph node, one lymph organ (thymus, spleen, and tonsils) or in just one area of a single organ outside of your lymph system.
Stage II: This is when there’s lymphoma in two or more lymph node groupings or lymph node organs on the same side of your diaphragm.
Stage III: This stage is when there’s cancer in lymph nodes or lymph tissue on both sides of your diaphragm.
Stage IV: DLBCL has spread to organs outside of your lymph system, like your bone marrow, liver, or lungs.
Your provider may refer to stage I and II DLBCL as “early stage” and stage III and IV DLBCL as “advanced stage.”
Management and Treatment
How is DLBCL treated?
One of the most common treatments for diffuse large B-cell lymphoma is R-CHOP. It combines the monoclonal antibody drug rituximab with three chemotherapy drugs and a corticosteroid.
This treatment is safe and effective, but doesn’t always work or keep DLBCL from coming back (recurring). Studies show relapses or recurrent cancer affect an estimated 30% to 40% of people with DLBCL who receive R-CHOP. If that happens, your provider may recommend the following treatments:
Second-line therapy and autologous stem cell transplant. Second-line therapy is intensive treatment with combined cancer drugs.
CAR T-cell therapy. This treatment is a type of immunotherapy that helps your T cells (a type of white blood cell) fight cancer more effectively.
Targeted therapy. This treatment targets the genetic changes or mutations that cause diffuse large B-cell lymphoma.
Outlook / Prognosis
What can I expect if I have DLBCL?
While some DLBCL can be life-threatening and difficult to treat, healthcare providers can often cure it using a combination of cancer drugs. Often, front-line or initial treatment sends DLBCL into complete remission. This means there are no signs and symptoms of cancer. Front-line treatment cures about 60% of people with DLBCL. In general, people who are cancer-free two years after their diagnosis can expect to live as long as most people in their age group.
According to the National Cancer Institute, 64.7% of all people with DLBCL are alive five years after diagnosis. Like many kinds of cancer, survival rates increase for people with early-stage cancer.
The overall 5-year survival rate for diffuse large B-cell lymphoma (DLBCL) is around 60-65%. This means that roughly 60-65 out of every 100 people diagnosed with DLBCL are still alive five years after their diagnosis. However, survival rates can vary significantly based on factors like the stage of the cancer at diagnosis and the patient's overall health.
Here's a more detailed breakdown:
Overall Survival:
The Canadian Cancer Society reports that the 5-year relative survival rate for DLBCL is approximately 60%. The Cleveland Clinic states that the National Cancer Institute reports 64.7% of people with DLBCL are alive five years after diagnosis.
Stage at Diagnosis:
MyLymphomaTeam notes that survival rates are higher for earlier stages of DLBCL: "Stage 1 — 79.2 percent, Stage 2 — 75.5 percent, Stage 3 — 67.4 percent, Stage 4 — 55.2 percent.".
Treatment and Prognosis:
Treatment, particularly with regimens like R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), is often very effective, and many people with DLBCL are cured. People who are cancer-free two years after diagnosis are expected to have a life expectancy similar to that of the general population.
Factors Influencing Survival:
Factors like the patient's age, overall health, and the specific subtype of DLBCL can also affect survival rates. For example, younger patients and those with lower IPI (International Prognostic Index) scores tend to have better outcomes.
Prevention
Can diffuse large B-cell lymphoma be prevented?
There’s no guaranteed way to prevent DLBCL, and nothing you can do about risk factors you can’t control, like having an immunodeficiency. But you can take steps to reduce your risk of developing certain infections linked to DLBCL, like hepatitis and HIV. You can also work to maintain a BMI (body mass index) that’s healthy for you.
Living With
How do I take care of myself?
It can be stressful and exhausting to live with any form of cancer, including diffuse large B-cell lymphoma. You must do what you can to take care of yourself throughout DLBCL treatment. Here are some suggestions:
Focus on nutrition. Know what foods to eat and avoid, so you’re nourishing your body.
Rest. Fatigue is the most common side effect of DLBCL treatment. Get as much rest as you can.
Develop an exercise routine. Gentle exercise may help you cope with stress.
Find support. Diffuse large B-cell lymphoma is a rare condition. You may feel as if no one understands what you’re going through. Connecting with people who are in your situation may help.
When should I see my healthcare provider?
You’ll see your healthcare provider throughout your treatment. They’ll monitor your health and check how the treatment is working.
Afterward, you may see your provider every three to four months for the first two years and then less frequently for the next three years. That’s because diffuse large B-cell lymphoma may come back. Contact your healthcare provider if you notice changes in your body that may mean the cancer has recurred.
When should I go to the emergency room?
Cancer treatments for DLBCL, including chemotherapy and immunotherapy, may have strong side effects. Your healthcare provider will advise you on how to manage them and prescribe medications to help. Still, you should go to the emergency room if you have:
Side effects that are stronger than you expected
A fever higher than 100.4 degrees Fahrenheit (38 degrees Celsius)
Chills that don’t go away
Abdominal pain
Persistent diarrhea
What questions should I ask my healthcare provider about DLBCL?
Questions you may want to ask include:
What type of diffuse large B-cell lymphoma do I have?
What’s this cancer’s stage?
What treatments will I need?
What treatment side effects can I expect?
Will this treatment cure the cancer?
What treatments are available if the cancer comes back?
Can you refer me to a support group for people who have this kind of cancer?
Complications
Complications of diffuse large B-cell lymphoma can include side effects of treatment and risk of relapse.
Side effects of treatment
Treatments for diffuse large B-cell lymphoma may have side effects. These may include nausea, vomiting, fatigue, fever, rash, diarrhea, and others. Harmful side effects from treatments may include:
Bone marrow suppression. When the bone marrow is suppressed, it can't produce enough blood cells, including white blood cells. White blood cells help fight infections, so with a lower amount, you are at a higher risk of infections.
Febrile neutropenia. Febrile neutropenia is a serious condition that can happen in people being treated for cancer. Febrile means having a fever. Neutropenia means having a low number of neutrophils, which are white blood cells that help fight infections. In febrile neutropenia, the body is trying to fight an infection, but doesn't have enough white blood cells.
Medicine toxicity. Some medicines used to treat cancer can be harmful to the body. They can cause organ damage and other issues. Whether a medicine is toxic depends on the type and how much you take. There are many different medicine options, so your healthcare team can work with you to find the best ones for you.
Reactivating viruses. If you have had a virus such as hepatitis B or hepatitis C in the past, some treatments can cause the virus to become active again. This can lead to liver inflammation, liver damage, and other complications.
Tumor lysis syndrome. Tumor lysis syndrome is a serious condition that can happen when cancer cells break down quickly during or after treatment. When these cells die, they release substances into the bloodstream that can overwhelm the body. This can lead to problems with the kidneys and other organs.
Medicines may be given to treat or prevent harmful side effects.
Fenbendazole as a Treatment for Diffuse Large B-Cell Lymphoma
Case Presentation
An 83-year-old male presented with heartburn, trouble swallowing, and fatigue. An Esophagogastroduodenoscopy (EGD) revealed a superficial duodenal ulcer, which was biopsied and revealed DLBCL, GCB subtype. Fluorescence in Situ Hybridization (FISH) was negative for c-MYC, BCL2, and BCL6. A Positron Emission Tomography/Computed Tomography (PET/CT) scan revealed hypermetabolic activity in the distal gastric antrum, proximal duodenum, peri-aortic lymph node, and pulmonary nodules. The patient was staged as stage IVa and was offered chemotherapy, but he declined treatment due to the side effect profile.
He started to take fenbendazole 1g daily based on self-research (used to take between 1-6 tabs daily based on his symptoms). After 6 months, he cut down on fenbendazole to 1-3 tabs daily due to peripheral neuropathy. He presented to his primary care physician, who obtained a repeated CT scan, which revealed smaller mediastinal lymph nodes. After 2 months, he decided to follow up with oncology, so he had a repeated PET/CT scan, which revealed improved lymphadenopathy from prior scans (Figure 1).
Figure 1: In the next 3 months, he continued to taper down fenbendazole and reached 3 pills weekly. A repeated PET/CT scan revealed interval improvement in his disease with no new lesion seen (Figure 2).
In the next 3 months, he continued to taper down fenbendazole and reached 3 pills weekly. A repeated PET/CT scan revealed interval improvement in his disease with no new lesion seen (Figure 2).
Figure 2:
Discussion
Fenbendazole is a broad-spectrum benzimidazole; it is an anthelmintic drug that is commonly used to treat animals’ parasitic infections [2,3]. Fenbendazole acts on parasites by binding and disrupting tubulin microtubules [2]. Microtubules play a crucial role in cell division, intracellular trafficking, motility, and modulating cellular shape. As a result, drugs that target microtubules have been widely used as a cancer treatment, such as Vinca alkaloids, paclitaxel, and others [2,3].
Several studies were done to evaluate the anti-neoplastic effect of fenbendazole. Dogra et al [3] performed a study on mice that demonstrated the anti-tumor effect of fenbendazole through disruption of microtubule dynamics, p53 activation, and modulation of different cellular pathways’ genes. Moreover, Bai et al [4] reported that fenbendazole also had some anti-brain tumor activity in mice [4]. Gao et al [5] performed a study on 20 SCID mice, which were exposed to 4 different diets: standard diet, diet plus vitamins, diet plus fenbendazole, and diet plus both vitamins and fenbendazole. All mice had implantation of lymphoma cells 2 weeks after starting the diet. This study showed that only the group that had both vitamins and fenbendazole experienced a significant tumor growth inhibition. On the other hand, Duan et al [2] performed a study to evaluate fenbendazole effect on EMT6 mice mammary tumor cells in vitro and solid tumors in mice in vivo. Their study showed that fenbendazole was toxic to EMT6 cells in vitro, though it did not alter the growth of EMT6 tumors. As a result, the study did not provide any evidence that fenbendazole can be used as a cancer therapy [2].
In our case, it is clear that the patient had a regression in his disease, which is thought to be due to fenbendazole. Whether it’s related to Fenbendazole or other factors is still unknown. Further studies are required to understand the anti-tumor effect of fenbendazole.
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