Lymphoma is a type of cancer that affects white blood cells called lymphocytes in the lymphatic system. Stage 4 lymphoma is the most advanced stage of lymphoma, occurring when the disease is widespread in the lymphatic system, bone marrow, and even other organs such as the lungs or liver.e60dc2a1-f33c-4a05-9b50-8e3e8e597629e13c4c5c-d13b-43a6-99bf-9631cc44b2e9 Treatment of stage 4 lymphoma depends on the lymphoma type and may involve a combination of therapies, including chemotherapy, radiation therapy, stem cell transplantation, targeted therapy, immunotherapy, and surgery. Prognosis for stage 4 lymphoma also depends on the cancer type — along with patient age, overall health, and response to treatment.
Types of Stage 4 Lymphoma Types There are two main categories of lymphoma:e60dc2a1-f33c-4a05-9b50-8e3e8e59762931f5a282-894d-4aab-b63b-c93854b1737ce60dc2a1-f33c-4a05-9b50-8e3e8e597629b24b1a8f-061a-4560-ba08-94ea4ce68d50 Hodgkin lymphoma (formerly known as Hodgkin disease), which involves an abnormal type of lymphocyte called Reed-Sternberg cells Non-Hodgkin lymphoma, which does not contain Reed-Sternberg cells Both Hodgkin and non-Hodgkin lymphomas have a number of subtypes, which differ depending on the cells and tissues the cancer affects and how quickly they grow. Hodgkin Lymphoma Most Hodgkin lymphomas — 95 percent — are the “classic” types. There are four subtypes of classic Hodgkin lymphomas:e60dc2a1-f33c-4a05-9b50-8e3e8e597629a7557d94-63d1-41b2-b564-da11f737ce18 Nodular Sclerosing Hodgkin Lymphoma This is the most common subtype of classic Hodgkin lymphoma, and it affects the lymph nodes in the central part of the chest. Mixed Cellularity Hodgkin Lymphoma This subtype is marked by lymph nodes carrying a mix of cell types, including many Reed-Sternberg cells. Lymphocyte-Rich Classic Hodgkin Lymphoma About 6 percent of Hodgkin lymphomas are of this subtype, which is characterized by a higher number of normal lymphocytes along with Reed-Sternberg cells. Lymphocyte-Depleted Hodgkin Lymphoma About 1 percent of people with Hodgkin lymphoma have this subtype, which is characterized by many abnormal lymphocytes in place of normal lymphocytes. The slow-growing nodular lymphocyte-predominant Hodgkin lymphoma makes up the other 5 percent of Hodgkin cases. This type grows more slowly and is more common in people in their twenties. Non-Hodgkin Lymphoma Non-Hodgkin lymphoma is far more common than Hodgkin lymphoma. It has dozens of subtypes that differ in terms of aggressiveness, response to treatment, and affected cell types. Common non-Hodgkin lymphomas include:e60dc2a1-f33c-4a05-9b50-8e3e8e597629cb7977b0-c3bc-40e8-8756-3f024839b3d6e60dc2a1-f33c-4a05-9b50-8e3e8e59762948341ed7-002f-45ca-9cb2-cf793ab869d1 Diffuse large B-cell lymphoma, the most common type of non-Hodgkin lymphoma, which grows quickly in lymph nodes and often in other organs Follicular lymphoma, a slower-growing form that is characterized by enlarged lymph nodes and large cancel cells that may appear U-shapede60dc2a1-f33c-4a05-9b50-8e3e8e597629154bba87-f054-4796-9e14-9579fd233632 Mantle cell lymphoma , a rare and aggressive form that often affects the lymph nodes, bone marrow, spleen, and gastrointestinal tract Burkitt lymphoma, a highly aggressive form that primarily affects children and young adults Peripheral T-cell lymphomas, a diverse group of aggressive lymphomas that arise from mature T-cells in the thymus gland and travels to the lymph nodes, bone marrow, or spleen Small lymphocytic lymphoma, a slow-growing cancer that’s closely related to chronic lymphocytic leukemia and primarily involves the lymph nodes and spleen Lymphoma Staging Lymphoma is staged based on where in the body the cancer has spread. In stage 1, the cancer is limited to a single lymph node or a group of adjacent lymph nodes. Stage 2 involves two or more groups of lymph nodes on the same side of the diaphragm. In stage 3, the cancer has spread to lymph nodes on both sides of the diaphragm and may involve the spleen. Stage 4 involves widespread disease that includes other organs.e60dc2a1-f33c-4a05-9b50-8e3e8e597629a8519240-7415-4ead-9e08-5ae0465aca41
Signs and Symptoms of Stage 4 Lymphoma Symptoms Symptoms can vary depending on the type of lymphoma, but common signs include:e60dc2a1-f33c-4a05-9b50-8e3e8e597629a0307efb-a78b-461b-8229-e73921abdad6 Enlarged lymph nodes in the neck, under the arm, or in the groin Persistent fatigue Unexplained weight loss Drenching night sweats Itchy skin Fever without an infection Stage 4 lymphoma can cause a range of other symptoms depending on the organs and parts of the body that are affected:e60dc2a1-f33c-4a05-9b50-8e3e8e597629ccc2402e-6b80-409d-b1df-61f3a008100b Abdominal pain and swelling, loss of appetite, or feeling full after a small meal, if the cancer involves organs in the abdominal cavity Breathing difficulties, including coughing and chest pain, if lymphoma affects the mediastinum (the area between the lungs) Gastrointestinal issues such as nausea, vomiting, abdominal pain, or changes in bowel habits if the lymphoma affects the stomach or intestines Neurological symptoms such as headaches, trouble thinking, changes in vision, personality changes, seizures, facial numbness, or trouble speaking if lymphoma affects the central nervous system
How Is Stage 4 Lymphoma Diagnosed? Diagnosis Diagnosing lymphoma involves a combination of medical history review, physical examinations, blood tests, imaging tests, and biopsies (the process of removing a small tissue sample for viewing under a microscope):e60dc2a1-f33c-4a05-9b50-8e3e8e5976291d8492ff-b99a-4e1d-bc3d-fed498b8bd5ee60dc2a1-f33c-4a05-9b50-8e3e8e5976299e169125-089a-4747-b630-222479058a35 Medical History and Physical Examination Your healthcare provider will thoroughly review your medical history, including symptoms, previous illnesses, possible risk factors, and family history to understand the likelihood of you having lymphoma. They will then perform a physical exam to check for signs of lymphoma, such as swollen lymph nodes, enlarged spleen or liver, and other abnormalities. Biopsy To confirm suspected lymphoma, your provider will perform a biopsy by taking a sample of a lymph node or, in some cases, an entire lymph node, for examination. Though unlikely, your provider may perform a less invasive procedure, such as a core needle biopsy or fine-needle aspiration, which involves using a thin needle to extract a small sample of tissue from a suspicious lymph node. Biopsies can often determine the type of lymphoma you have, but additional lab tests on the samples, such as immunochemistry, may be needed. Blood Tests After confirming you have cancer, your provider may order certain blood tests to determine how advanced the lymphoma is, evaluate your overall health, and assess the function of various organs, such as the liver and kidneys. Your provider may also order a complete blood count to check for abnormalities in blood cell counts. Imaging Tests Along with the blood tests, your provider may also order imaging tests to understand where lymphoma is occurring in your body. These include CT (computerized tomography) and PET (positron emission tomography) scans to visualize enlarged lymph nodes and other organs to see if they contain cancerous cells.e60dc2a1-f33c-4a05-9b50-8e3e8e597629443dd0b3-a45d-4fd2-80f7-d4b9b72e90d4 MRI scans aren’t used as often for lymphoma, but they can help determine if lymphoma is affecting the spinal cord or brain. Your provider will order additional tests to determine the extent of the disease and whether it’s in stage 4 (whether it has spread to the spleen, liver, or other organs). These may include:e60dc2a1-f33c-4a05-9b50-8e3e8e59762970ad4cab-5658-4a80-b2ae-508700f8862d Bone marrow aspiration and biopsy to see if the lymphoma affects your bone marrow Lumbar puncture (spinal tap) to see if lymphoma has spread to your central nervous system Pleural or peritoneal fluid sampling to see if lymphoma is in your chest or abdomen and causing a buildup of fluid
Treatment Options for Stage 4 Lymphoma Treatment Treatment for stage 4 lymphoma often involves a combination of therapies, including chemotherapy, radiation therapy, stem cell transplantation, and more. Chemotherapy Chemotherapy is the use of powerful drugs to kill or inhibit the growth of cancer cells throughout the body. These medicines are usually given as an IV infusion or in pill form. A number of different drug combinations may be used to treat stage 4 Hodgkin lymphoma, such as:e60dc2a1-f33c-4a05-9b50-8e3e8e59762906b1cf86-3496-4e98-a4ba-c3ec5bffba62 ABVD, made up of doxorubicin hydrochloride (Adriamycin), bleomycin, vinblastine sulfate, and dacarbazinee60dc2a1-f33c-4a05-9b50-8e3e8e5976297a00dc80-8ec9-431e-bc0d-9f06b2da4313 BEACOPP, made up of bleomycin, etoposide phosphate, doxorubicin hydrochloride (Adriamycin), cyclophosphamide, vincristine sulfate (Oncovin), procarbazine hydrochloride, and prednisonee60dc2a1-f33c-4a05-9b50-8e3e8e597629249b5477-ba29-4014-8333-52525c6d8d8c EPOCH, made up of etoposide phosphate, prednisone, vincristine sulfate (Oncovin), cyclophosphamide, and doxorubicin hydrochloride (hydroxydaunomycin)e60dc2a1-f33c-4a05-9b50-8e3e8e5976292c95a5cd-6dfb-4914-9969-32c60e241238 Researchers are still learning more about which chemotherapy regimens are most effective for specific types of lymphoma. Side effects of these medications may include:e60dc2a1-f33c-4a05-9b50-8e3e8e597629a94a1270-25f6-461b-abad-1bd775f67b7de60dc2a1-f33c-4a05-9b50-8e3e8e5976293aa9ba32-8abc-44b0-b5fb-c6475b347c50 Anemia Breathlessness Bruising, bleeding gums, or nosebleeds Chills Constipation Diarrhea Hair loss Fatigue Fever Increased risk of infection Loss of appetite Mouth sores Nausea Risk of blood clots Skin problems, such as a rash or blistering, thickening, or itching of the skin. Weight gain or loss Heart, liver, or lung changes Radiation Therapy Radiation therapy uses high-dose X-rays or other forms of radiation to target and destroy cancer cells and keep them from growing. Your doctor may use radiation therapy to either attempt to cure the cancer or to help treat symptoms of lymphoma.e60dc2a1-f33c-4a05-9b50-8e3e8e5976296bdf2d7d-3894-40cf-8e1f-504fd7c83fbc Curative radiation therapy is given with the aim of achieving remission (no evidence of the disease in your body). It’s used to treat localized disease or to shrink tumors before, during, or after chemotherapy. When radiation therapy is used to control symptoms of lymphoma, such as pain, this is called palliative radiotherapy.e60dc2a1-f33c-4a05-9b50-8e3e8e59762936617c82-38b7-4435-abeb-18ad096f98c6 Common side effects include:e60dc2a1-f33c-4a05-9b50-8e3e8e597629048c9988-e674-4369-9f68-5acfa57dead9e60dc2a1-f33c-4a05-9b50-8e3e8e59762937ace7eb-4842-489a-8b1b-ebb312965dc0 Redness, blistering, or peeling of the skin where radiation is given Fatigue Nausea Dizziness More serious side effects include:e60dc2a1-f33c-4a05-9b50-8e3e8e597629048c9988-e674-4369-9f68-5acfa57dead9e60dc2a1-f33c-4a05-9b50-8e3e8e59762937ace7eb-4842-489a-8b1b-ebb312965dc0 Lung or heart damage from radiation to the chest Thyroid problems from radiation to the neck Headache, memory loss, and personality changes from radiation to the brain Formation of other cancers Targeted Therapy Targeted therapy fights cancer by specifically targeting certain molecules involved in cancer growth. Some types of targeted therapies include the following: Monoclonal Antibodies These are immune system proteins made in the laboratory to target and kill cancer cells, block their growth, or keep them from spreading. Sometimes a monoclonal antibody is linked to a chemotherapy drug (called an antibody-drug conjugate), allowing the drug to be delivered directly to the cancer cell.e60dc2a1-f33c-4a05-9b50-8e3e8e597629ee8bd1e7-4266-41ec-b149-35b132d095f5 Proteasome Inhibitors These medications block the activity of proteins called proteasomes that remove proteins in cells that are no longer needed. Blocking proteasomes allows proteins to build up in cells, potentially killing cancer cells. Kinase Inhibitors These drugs block certain enzymes that control cell growth, helping to keep lymphoma cells from growing.e60dc2a1-f33c-4a05-9b50-8e3e8e59762987898c5e-0f2d-4091-8edf-36e3647409a2 Examples of targeted therapies used to treat stage 4 lymphoma include:e60dc2a1-f33c-4a05-9b50-8e3e8e597629f8690d0a-49ee-4323-a582-1cfc53a3d666 brentuximab vedotin (Adcetris) copanlisib (Aliqopa) crizotinib (Xalkori) ibrutinib (Imbruvica) idelalisib (Zydelig) mogamulizumab (Poteligeo) polatuzumab vedotin (Polivy) rituximab (Rituxan) Targeted therapy drugs may have side effects. The types of side effects experienced will depend on the type of drug and what it targets.e60dc2a1-f33c-4a05-9b50-8e3e8e597629e0a47bfa-7ec4-4394-ac6a-0521643601ab Some common side effects include:e60dc2a1-f33c-4a05-9b50-8e3e8e59762960dc7c78-a28b-4bc4-9dbc-e476afe6c14ce60dc2a1-f33c-4a05-9b50-8e3e8e597629ea937a72-63d2-4050-bbfd-d161a8a365f9 Cough Diarrhea or constipation Flu-like symptoms such as fever and chills Fatigue Headache Heart problems Infection Kidney problems Liver problems Loss of appetite and weight loss Low blood cell counts Nausea and vomiting Nerve damage Joint pain Skin rashes, redness, itching, or dryness Allergic reaction to the medication Immunotherapy Immunotherapy aims to enhance the body’s immune system to recognize and attack cancer cells. Types of immunotherapy used to treat stage 4 lymphoma include: CAR T-Cell Therapy This is a type of immunotherapy where your doctor will remove some of your T cells, add special receptors to their surfaces in a laboratory, and then return the modified cells back to your body to bind to and kill cancer cells.e60dc2a1-f33c-4a05-9b50-8e3e8e597629afb4529d-1849-407f-807a-f601671000da Researchers are getting better at determining which lymphoma patients will respond well to CAR T-cell therapy before beginning treatment.e60dc2a1-f33c-4a05-9b50-8e3e8e5976293ef5f834-3d4f-48cd-aa22-f66e6b6287f0e60dc2a1-f33c-4a05-9b50-8e3e8e5976293c8ec31e-aeb3-4c97-b33b-87b06265b087 Checkpoint Inhibitors PD-1 is a type of checkpoint protein on cell surfaces that helps prevent the body’s immune system from attacking normal, healthy cells. Some cancer cells also have these proteins and can therefore “hide” from the immune system. PD-1 inhibitors such as nivolumab (Opdivo) and pembrolizumab (Keytruda) block this checkpoint protein and allow the body’s immune system to better attack cancer cells.e60dc2a1-f33c-4a05-9b50-8e3e8e5976298a30e35d-58b1-451b-9941-36475c59f5a9 Immunomodulating Drugs Medications such as thalidomide (Thalomid) and lenalidomide (Revlimid) are a type of immunotherapy called immunomodulating drugs. They are given to patients with lymphoma who have not responded to other treatments. It’s not yet clear to researchers exactly how these drugs work, but they are thought to work against cancer by affecting parts of the immune system.e60dc2a1-f33c-4a05-9b50-8e3e8e5976292288fabe-d28b-41a5-ba7f-1433d5f36df8 Stem Cell Transplantation Stem cell transplantation involves the infusion of healthy stem cells (immature blood cells) to replace damaged or destroyed bone marrow. Also known as a bone marrow transplant, it’s typically used after high-dose chemotherapy or radiation therapy to restore the bone marrow’s ability to produce blood cells.e60dc2a1-f33c-4a05-9b50-8e3e8e5976297295caa3-7295-4c64-9abc-6afe79cd5b87 Stem cells are removed from the blood or bone marrow of the patient or a donor, and then frozen and stored. After chemotherapy or radiation, these stem cells are thawed and infused back into the patient, where they grow into healthy blood cells.e60dc2a1-f33c-4a05-9b50-8e3e8e5976297295caa3-7295-4c64-9abc-6afe79cd5b87 Surgery For certain lymphomas that are either aggressive or very slow-growing, surgery may be used to remove the cancer. The type of surgery depends on the type of lymphoma and where it has formed in the body.e60dc2a1-f33c-4a05-9b50-8e3e8e5976297295caa3-7295-4c64-9abc-6afe79cd5b87 Clinical Trials Clinical trials for lymphoma are studies aiming to improve current treatments or test new ones. Patients who participate in a clinical trial may have access to new treatments that are not otherwise available. Eligibility is different for each trial, with some only enrolling patients who haven’t received treatment yet while others might only include patients for whom other treatments have not worked. Speak to your doctor to learn more about joining a clinical trial, or you can search for trials online at ClinicalTrials.gov .e60dc2a1-f33c-4a05-9b50-8e3e8e5976297295caa3-7295-4c64-9abc-6afe79cd5b87
Stage 4 Lymphoma Prognosis Prognosis and Outlook The prognosis for stage 4 lymphoma varies based on factors such as lymphoma type, age, overall health, and response to treatment. Advances in medical research and treatment options have significantly improved survival rates in recent years. The overall five-year relative survival rate (the percentage of people who will live five years or more after being diagnosed with the disease compared with people without the disease) for Hodgkin lymphoma is 89 percent. For stage 4 Hodgkin lymphoma, the five-year relative survival rate is reduced to 81 percent.e60dc2a1-f33c-4a05-9b50-8e3e8e597629c7b265bd-5f63-45e7-99ba-9e67a6e64c00 Non-Hodgkin lymphoma is typically more aggressive and therefore has a poorer prognosis. The overall five-year relative survival rate for non-Hodgkin lymphoma is 74 percent. For stage 4 non-Hodgkin lymphoma, the relative five-year relative survival rate is 64 percent.e60dc2a1-f33c-4a05-9b50-8e3e8e597629e0875ef7-4b18-4baa-bf44-0b6223e9cdb4 Factors that affect survival include:e60dc2a1-f33c-4a05-9b50-8e3e8e59762940504917-e2ce-49f6-a489-456fb925533a Lymphoma Subtype Patients with indolent or slow-growing subtypes such as follicular lymphoma may live with the disease for many years. Some subtypes such as diffuse large B-cell lymphoma may respond better to treatment. Age, Sex, and General Health Patients who are healthy, under 60 years old, and female have a better prognosis. Lactate Dehydrogenase (LDH) Levels Higher LDH levels in the blood indicate poorer survival. Extent of the Disease Survival is reduced at higher stages with more widespread disease and more organs affected.
Complications of Stage 4 Lymphoma Complications Some people with stage 4 lymphoma experience other health problems as a result of the disease or from treatment side effects. These may include:e60dc2a1-f33c-4a05-9b50-8e3e8e59762913c46b25-3395-493d-9e3b-0c2593479435e60dc2a1-f33c-4a05-9b50-8e3e8e597629b6e83942-f1fc-4c4b-972a-19afded39258 A weakened immune system Infertility Heart disease Lung disease Stroke Thyroid problems A second cancer
How Many People Have Stage 4 Lymphoma? Statistics The American Cancer Society estimates that in 2024, there were more than 8,500 new cases of Hodgkin lymphoma, with about 900 deaths.e60dc2a1-f33c-4a05-9b50-8e3e8e5976297f6d9766-7de1-4f56-8122-0198f95fceaf For non-Hodgkin lymphoma, there were about 80,000 new cases in both adults and children, with about 20,000 deaths.e60dc2a1-f33c-4a05-9b50-8e3e8e5976295ca04f81-82be-4e77-9ee8-adee64b6d80c According to a national database of people with lymphoma in the United States, about 23 percent of patients with Hodgkin lymphoma have stage 4 disease.e60dc2a1-f33c-4a05-9b50-8e3e8e5976299c3e4af5-18a4-4d61-a82f-4dead1446993 For non-Hodgkin lymphoma, 36 percent of patients have stage 4 disease.e60dc2a1-f33c-4a05-9b50-8e3e8e59762952e7d112-c442-4e3f-ab34-c125928d3a6c The Takeaway Stage 4 lymphoma is the most advanced stage of the disease, characterized by its spread to other areas of the body like the lungs or liver. Many advanced treatment options are available to manage stage 4 lymphoma and improve survival, although the response to treatment depends on a variety of factors, including the type of lymphoma, age, and overall health. It’s important for individuals with symptoms that may suggest stage 4 lymphoma — such as unexplained weight loss, persistent fatigue, fever without an infection, or swollen lymph nodes — to seek immediate evaluation from a healthcare professional for accurate diagnosis and prompt treatment.
Resources We Trust Mayo Clinic: Hodgkin Lymphoma (Hodgkin Disease)Cleveland Clinic: Non-Hodgkin LymphomaAmerican Cancer Society: Stem Cell or Bone Marrow TransplantMoffitt Cancer Center: What Are the Different Stages of Lymphoma?Get Palliative Care: Leukemia, Lymphoma, and Palliative Care