Non-Hodgkin Lymphoma

Non-Hodgkin lymphoma is a disease in which malignant (cancer) cells form in the lymph system.

Non-Hodgkin lymphoma is a type of cancer that forms in the lymph system. The lymph system is part of the immune system. It helps protect the body from infection and disease.

The lymph system is made up of the following:

• Lymph: Colorless, watery fluid that travels through the lymph vessels and carries lymphocytes (white blood cells). There are three types of lymphocytes:
  • B lymphocytes that make antibodies to help fight infection. Also called B cells. Most types of non-Hodgkin lymphoma begin in B lymphocytes.
  • T lymphocytes that help B lymphocytes make the antibodies that help fight infection. Also called T cells.
  • Natural killer cells that attack cancer cells and viruses. Also called NK cells.
• Lymph vessels: A network of thin tubes that collect lymph from different parts of the body and return it to the bloodstream.
• Lymph nodes: Small, bean-shaped structures that filter lymph and store white blood cells that help fight infection and disease. Lymph nodes are found along a network of lymph vessels throughout the body. Groups of lymph nodes are found in the neck, underarm, mediastinum, abdomen, pelvis, and groin.
• Spleen: An organ that makes lymphocytes, stores red blood cells and lymphocytes, filters the blood, and destroys old blood cells. The spleen is on the left side of the abdomen near the stomach.
• Thymus: An organ in which T lymphocytes mature and multiply. The thymus is in the chest behind the breastbone.
• Tonsils: Two small masses of lymph tissue at the back of the throat. There is one tonsil on each side of the throat.
• Bone marrow: The soft, spongy tissue in the center of certain bones, such as the hip bone and breastbone. White blood cells, red blood cells, and platelets are made in the bone marrow.

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The lymph system is part of the body's immune system and is made up of tissues and organs that help protect the body from infection and disease. These include the tonsils, adenoids (not shown), thymus, spleen, bone marrow, lymph vessels, and lymph nodes. Lymph tissue is also found in many other parts of the body, including the small intestine.

Lymph tissue is also found in other parts of the body such as the lining of the digestive tract, bronchus, and skin.

There are two general types of lymphomas: Hodgkin lymphoma and non-Hodgkin lymphoma. This summary is about the treatment of non-Hodgkin lymphoma in adults, including during pregnancy.

Non-Hodgkin lymphoma can be indolent or aggressive.

Non-Hodgkin lymphoma grows and spreads at different rates and can be indolent or aggressive. Indolent lymphoma tends to grow and spread slowly, and has few signs and symptoms. Aggressive lymphoma grows and spreads quickly, and has signs and symptoms that can be severe. The treatments for indolent and aggressive lymphoma are different.

This summary is about the following types of non-Hodgkin lymphoma:

Older age, being male, and having a weakened immune system can increase the risk of non-Hodgkin lymphoma.

Anything that increases a person's chance of getting a disease is called a risk factor. Not every person with one or more of these risk factors will develop non-Hodgkin lymphoma, and it can develop in people who don't have any known risk factors. Talk with your doctor if you think you may be at risk.

These and other risk factors may increase the risk of certain types of non-Hodgkin lymphoma:

• Being older, male, or White.
• Having one of the following medical conditions that weakens the immune system:
  • An inherited immune disorder (such as hypogammaglobulinemia or Wiskott-Aldrich syndrome).
  • An autoimmune disease (such as rheumatoid arthritis, psoriasis, or Sjögren syndrome).
  • HIV/AIDS.
  • Human T-lymphotrophic virus type I or Epstein-Barr virus infection.
  • Helicobacter pylori infection.
• Taking immunosuppressant drugs after an organ transplant.

Signs and symptoms of non-Hodgkin lymphoma include swollen lymph nodes, fever, drenching night sweats, weight loss, and fatigue.

These signs and symptoms may be caused by non-Hodgkin lymphoma or by other conditions. Check with your doctor if you have any of the following:

• Swelling in the lymph nodes in the neck, underarm, groin, or stomach.
• Fever for no known reason.
• Drenching night sweats.
• Feeling very tired.
• Weight loss for no known reason.
• Skin rash or itchy skin.
• Pain in the chest, abdomen, or bones for no known reason.

When fever, drenching night sweats, and weight loss occur together, this group of symptoms is called B symptoms.

Other signs and symptoms of non-Hodgkin lymphoma may occur and depend on the following:

• Where the cancer forms in the body.
• The size of the tumor.
• How fast the tumor grows.

Tests that examine the lymph system and other parts of the body are used to diagnose and stage non-Hodgkin lymphoma.

In addition to asking about your personal and family health history and doing a physical exam, your doctor may perform the following tests and procedures:

• Complete blood count (CBC): A procedure in which a sample of blood is drawn and checked for the following:
  • The number of red blood cells, white blood cells, and platelets.
  • The amount of hemoglobin (the protein that carries oxygen) in the red blood cells.
  • The portion of the sample made up of red blood cells.
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  Complete blood count (CBC). Blood is collected by inserting a needle into a vein and allowing the blood to flow into a tube. The blood sample is sent to the laboratory and the red blood cells, white blood cells, and platelets are counted. The CBC is used to test for, diagnose, and monitor many different conditions.
  

• Blood chemistry studies: A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease.
• LDH test: A procedure in which a blood sample is checked to measure the amount of lactic dehydrogenase. An increased amount of LDH in the blood may be a sign of tissue damage, lymphoma, or other diseases.
• Hepatitis B and hepatitis C test: A procedure in which a sample of blood is checked to measure the amounts of hepatitis B virus-specific antigens and/or antibodies and the amounts of hepatitis C virus-specific antibodies. These antigens or antibodies are called markers. Different markers or combinations of markers are used to determine whether a patient has a hepatitis B or C infection, has had a prior infection or vaccination, or is susceptible to infection. Patients who have been treated for hepatitis B virus in the past need continued monitoring to check if it has reactivated. Knowing whether a person has hepatitis B or C may help plan treatment.
• HIV test: A test to measure the level of HIV antibodies in a sample of blood. Antibodies are made by the body when it is invaded by a foreign substance. A high level of HIV antibodies may mean the body has been infected with HIV.
• CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, such as the neck, chest, abdomen, pelvis, and lymph nodes, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
• PET scan (positron emission tomography scan): A procedure to find malignant tumor cells in the body. A small amount of radioactive glucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.
• Bone marrow aspiration and biopsy: The removal of bone marrow and a small piece of bone by inserting a needle into the hipbone or breastbone. A pathologist views the bone marrow and bone under a microscope to look for signs of cancer.
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  Bone marrow aspiration and biopsy. After a small area of skin is numbed, a long, hollow needle is inserted through the patient's skin and hip bone into the bone marrow. A sample of bone marrow and a small piece of bone are removed for examination under a microscope.
  

• Lymph node biopsy: The removal of all or part of a lymph node. A pathologist views the tissue under a microscope to check for cancer cells. One of the following types of biopsies may be done:
  • Excisional biopsy: The removal of an entire lymph node.
  • Incisional biopsy: The removal of part of a lymph node.
  • Core biopsy: The removal of part of a lymph node using a wide needle.

If cancer is found, the following tests may be done to study the cancer cells:

• Immunohistochemistry: A laboratory test that uses antibodies to check for certain antigens (markers) in a sample of a patient’s tissue. The antibodies are usually linked to an enzyme or a fluorescent dye. After the antibodies bind to a specific antigen in the tissue sample, the enzyme or dye is activated, and the antigen can then be seen under a microscope. This type of test is used to help diagnose cancer and to help tell one type of cancer from another type of cancer.
• Cytogenetic analysis: A laboratory test in which the chromosomes of cells in a sample of blood or bone marrow are counted and checked for any changes, such as broken, missing, rearranged, or extra chromosomes. Changes in certain chromosomes may be a sign of cancer. Cytogenetic analysis is used to help diagnose cancer, plan treatment, or find out how well treatment is working.
• Immunophenotyping: A laboratory test that uses antibodies to identify cancer cells based on the types of antigens or markers on the surface of the cells. This test is used to help diagnose specific types of lymphoma.
• FISH (fluorescence in situ hybridization): A laboratory test used to look at and count genes or chromosomes in cells and tissues. Pieces of DNA that contain fluorescent dyes are made in the laboratory and added to a sample of a patient’s cells or tissues. When these dyed pieces of DNA attach to certain genes or areas of chromosomes in the sample, they light up when viewed under a fluorescent microscope. The FISH test is used to help diagnose cancer and help plan treatment.

Other tests and procedures may be done depending on the signs and symptoms seen and where the cancer forms in the body.

Certain factors affect prognosis (chance of recovery) and treatment options.

The prognosis and treatment options depend on the following:

• The patient's signs and symptoms, including whether or not they have B symptoms (fever for no known reason, weight loss for no known reason, or drenching night sweats).
• The stage of the cancer (the size of the cancer tumors and whether the cancer has spread to other parts of the body or lymph nodes).
• The type of non-Hodgkin lymphoma.
• The amount of lactate dehydrogenase (LDH) in the blood.
• Whether there are certain changes in the genes.
• The patient’s age, sex, and general health.
• Whether the lymphoma is newly diagnosed, continues to grow during treatment, or has recurred (come back).

For non-Hodgkin lymphoma during pregnancy, treatment options also depend on:

• The wishes of the patient.
• Which trimester of pregnancy the patient is in.
• Whether the baby can be delivered early.

Some types of non-Hodgkin lymphoma spread more quickly than others do. Most non-Hodgkin lymphomas that occur during pregnancy are aggressive. Delaying treatment of aggressive lymphoma until after the baby is born may lessen the mother's chance of survival. Immediate treatment is often recommended, even during pregnancy.

After non-Hodgkin lymphoma has been diagnosed, tests are done to find out whether cancer cells have spread within the lymph system or to other parts of the body.

The process used to find out the type of cancer and if cancer cells have spread within the lymph system or to other parts of the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage of the disease in order to plan treatment. The results of the tests and procedures done to diagnose non-Hodgkin lymphoma are used to help make decisions about treatment.

The following tests and procedures may also be used in the staging process:

• MRI (magnetic resonance imaging) with gadolinium: A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body, such as the brain and spinal cord. A substance called gadolinium is injected into the patient through a vein. The gadolinium collects around the cancer cells so they show up brighter in the picture. This procedure is also called nuclear magnetic resonance imaging (NMRI).
• Lumbar puncture: A procedure used to collect cerebrospinal fluid (CSF) from the spinal column. This is done by placing a needle between two bones in the spine and into the CSF around the spinal cord and removing a sample of the fluid. The sample of CSF is checked under a microscope for signs that the cancer has spread to the brain and spinal cord. This procedure is also called an LP or spinal tap.
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  Lumbar puncture. A patient lies in a curled position on a table. After a small area on the lower back is numbed, a spinal needle (a long, thin needle) is inserted into the lower part of the spinal column to remove cerebrospinal fluid (CSF, shown in blue). The fluid may be sent to a laboratory for testing.
  

For pregnant women with non-Hodgkin lymphoma, staging tests and procedures that protect the fetus from the harms of radiation are used. These tests and procedures include MRI (without contrast), lumbar puncture, and ultrasound.

There are three ways that cancer spreads in the body.

Cancer can spread through tissue, the lymph system, and the blood:

• Tissue. The cancer spreads from where it began by growing into nearby areas.
• Lymph system. The cancer spreads from where it began by getting into the lymph system. The cancer travels through the lymph vessels to other parts of the body.
• Blood. The cancer spreads from where it began by getting into the blood. The cancer travels through the blood vessels to other parts of the body.

The following stages are used for non-Hodgkin lymphoma:

Stage I

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Stage I adult lymphoma. Cancer is found in one or more lymph nodes in a group of lymph nodes or, in rare cases, cancer is found in the Waldeyer’s ring, thymus, or spleen. In stage IE (not shown), cancer has spread to one area outside the lymph system.

Stage I non-Hodgkin lymphoma is divided into stages I and IE.

In stage I, cancer is found in one of the following places in the lymph system:

• One or more lymph nodes in a group of lymph nodes.
• Waldeyer's ring.
• Thymus.
• Spleen.

In stage IE, cancer is found in one area outside the lymph system.

Stage III

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Stage III adult lymphoma. Cancer is found in groups of lymph nodes both above and below the diaphragm; or in a group of lymph nodes above the diaphragm and in the spleen.

In stage III non-Hodgkin lymphoma, cancer is found:

• in groups of lymph nodes both above and below the diaphragm; or
• in lymph nodes above the diaphragm and in the spleen.

Stage IV

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Stage IV adult lymphoma. Cancer (a) has spread throughout one or more organs outside the lymph system; or (b) is found in two or more groups of lymph nodes that are either above the diaphragm or below the diaphragm and in one organ that is outside the lymph system and not near the affected lymph nodes; or (c) is found in groups of lymph nodes above the diaphragm and below the diaphragm and in any organ that is outside the lymph system; or (d) is found in the liver, bone marrow, more than one place in the lung, or cerebrospinal fluid (CSF). The cancer has not spread directly into the liver, bone marrow, lung, or CSF from nearby lymph nodes.

In stage IV non-Hodgkin lymphoma, cancer:

• has spread throughout one or more organs outside the lymph system; or
• is found in two or more groups of lymph nodes that are either above the diaphragm or below the diaphragm and in one organ that is outside the lymph system and not near the affected lymph nodes; or
• is found in groups of lymph nodes both above and below the diaphragm and in any organ that is outside the lymph system; or
• is found in the liver, bone marrow, more than one place in the lung, or cerebrospinal fluid (CSF). The cancer has not spread directly into the liver, bone marrow, lung, or CSF from nearby lymph nodes.

Non-Hodgkin lymphomas may be grouped for treatment according to whether the cancer is indolent or aggressive, whether affected lymph nodes are next to each other in the body, and whether the cancer is newly diagnosed or recurrent.

For more information on the types of indolent (slow-growing) and aggressive (fast-growing) non-Hodgkin lymphoma, see the General Information section.

Non-Hodgkin lymphoma can also be described as contiguous or noncontiguous:

• Contiguous lymphomas: Lymphomas in which the lymph nodes with cancer are next to each other.
• Noncontiguous lymphomas: Lymphomas in which the lymph nodes with cancer are not next to each other, but are on the same side of the diaphragm.

Non-Hodgkin lymphoma can recur (come back) after it has been treated.

The lymphoma may come back in the lymph system or in other parts of the body. Indolent lymphoma may come back as aggressive lymphoma. Aggressive lymphoma may come back as indolent lymphoma.

There are different types of treatment for patients with non-Hodgkin lymphoma.

Different types of treatment are available for patients with non-Hodgkin lymphoma. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

For pregnant women with non-Hodgkin lymphoma, treatment is carefully chosen to protect the fetus. Treatment decisions are based on the mother’s wishes, the stage of the non-Hodgkin lymphoma, and the trimester of the pregnancy. The treatment plan may change as the signs and symptoms, cancer, and pregnancy change. Choosing the most appropriate cancer treatment is a decision that ideally involves the patient, family, and health care team.

Patients with non-Hodgkin lymphoma should have their treatment planned by a team of health care providers who are experts in treating lymphomas.

Treatment will be overseen by a medical oncologist, a doctor who specializes in treating cancer, or a hematologist, a doctor who specializes in treating blood cancers. The medical oncologist may refer you to other health care providers who have experience and are experts in treating non-Hodgkin lymphoma and who specialize in certain areas of medicine. These may include the following specialists:

• Neurosurgeon.
• Neurologist.
• Radiation oncologist.
• Endocrinologist.
• Rehabilitation specialist.
• Fertility specialist.
• Other oncology specialists.

Treatment for non-Hodgkin lymphoma may cause side effects.

To learn more about side effects that begin during treatment for cancer, visit Side Effects.

Side effects from cancer treatment that begin after treatment and continue for months or years are called late effects. Treatment with chemotherapy, radiation therapy, or stem cell transplant for non-Hodgkin lymphoma may increase the risk of late effects.

Late effects of cancer treatment may include the following:

• Heart problems.
• Infertility (inability to have children).
• Loss of bone density.
• Neuropathy (nerve damage that causes numbness or trouble walking).
• A second cancer, such as:
  • Lung cancer.
  • Brain cancer.
  • Kidney cancer.
  • Bladder cancer.
  • Melanoma.
  • Hodgkin lymphoma.
  • Myelodysplastic syndrome.
  • Acute myeloid leukemia.

Some late effects may be treated or controlled. It is important to talk with your doctor about the effects cancer treatment can have on you. Regular follow-up to check for late effects is important.

The following types of treatment are used:

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid (intrathecal chemotherapy), an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). Combination chemotherapy is treatment using two or more anticancer drugs. Steroid drugs may be added, to lessen inflammation and lower the body's immune response.

Systemic combination chemotherapy is used for the treatment of non-Hodgkin lymphoma.

Intrathecal chemotherapy may also be used in the treatment of lymphoma that first forms in the testicles or sinuses (hollow areas) around the nose, diffuse large B-cell lymphoma, Burkitt lymphoma, lymphoblastic lymphoma, and some aggressive T-cell lymphomas. It is given to lessen the chance that lymphoma cells will spread to the brain and spinal cord. This is called CNS prophylaxis.

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Intrathecal chemotherapy. Anticancer drugs are injected into the intrathecal space, which is the space that holds the cerebrospinal fluid (CSF, shown in blue). There are two different ways to do this. One way, shown in the top part of the figure, is to inject the drugs into an Ommaya reservoir (a dome-shaped container that is placed under the scalp during surgery; it holds the drugs as they flow through a small tube into the brain). The other way, shown in the bottom part of the figure, is to inject the drugs directly into the CSF in the lower part of the spinal column, after a small area on the lower back is numbed.

When a pregnant woman is treated with chemotherapy for non-Hodgkin lymphoma, the fetus cannot be protected from being exposed to chemotherapy. Some chemotherapy regimens may cause birth defects if given in the first trimester.

For more information, see Drugs Approved for Non-Hodgkin Lymphoma.

Immunotherapy

Immunotherapy is a treatment that uses the patient’s immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body’s natural defenses against cancer.

• Immunomodulators: Lenalidomide is an immunomodulator used to treat non-Hodgkin lymphoma.
• CAR T-cell therapy: The patient's T cells (a type of immune system cell) are changed so they will attack certain proteins on the surface of cancer cells. T cells are taken from the patient and special receptors are added to their surface in the laboratory. The changed cells are called chimeric antigen receptor (CAR) T cells. The CAR T cells are grown in the laboratory and given to the patient by infusion. The CAR T cells multiply in the patient's blood and attack cancer cells. CAR T-cell therapy (such as axicabtagene ciloleucel or tisagenlecleucel) is used to treat large B-cell lymphoma that has not responded to treatment. CAR T-cell therapy is being studied to treat mantle cell lymphoma that has relapsed or not responded to treatment.

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CAR T-cell therapy. A type of treatment in which a patient’s T cells (a type of immune cell) are changed in the laboratory so they will bind to cancer cells and kill them. Blood from a vein in the patient’s arm flows through a tube to an apheresis machine (not shown), which removes the white blood cells, including the T cells, and sends the rest of the blood back to the patient. Then, the gene for a special receptor called a chimeric antigen receptor (CAR) is inserted into the T cells in the laboratory. Millions of the CAR T cells are grown in the laboratory and then given to the patient by infusion. The CAR T cells are able to bind to an antigen on the cancer cells and kill them.

For more information, see Drugs Approved for Non-Hodgkin Lymphoma.

Stem cell transplant

Stem cell transplant is a method of giving high doses of chemotherapy and/or total-body irradiation and then replacing blood-forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood or bone marrow of the patient (autologous transplant) or a donor (allogeneic transplant) and are frozen and stored. After the chemotherapy and/or radiation therapy is completed, the stored stem cells are thawed and given back to the patient through an infusion. These reinfused stem cells grow into (and restore) the body’s blood cells.

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Donor stem cell transplant. (Step 1): Four to five days before donor stem cell collection, the donor receives a medicine to increase the number of stem cells circulating through their bloodstream (not shown). The blood-forming stem cells are then collected from the donor through a large vein in their arm. The blood flows through an apheresis machine that removes the stem cells. The rest of the blood is returned to the donor through a vein in their other arm. (Step 2): The patient receives chemotherapy to kill cancer cells and prepare their body for the donor stem cells. The patient may also receive radiation therapy (not shown). (Step 3): The patient receives an infusion of the donor stem cells.

New types of treatment are being tested in clinical trials.

This summary section describes treatments that are being studied in clinical trials. It may not mention every new treatment being studied. Information about clinical trials is available from the NCI website.

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country. Information about clinical trials supported by NCI can be found on NCI’s clinical trials search webpage. Clinical trials supported by other organizations can be found on the ClinicalTrials.gov website.

Follow-up tests may be needed.

As you go through treatment, you will have follow-up tests or check-ups. Some tests that were done to diagnose or stage the cancer may be repeated to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back).

Indolent Non-Hodgkin Lymphoma During Pregnancy

Women who have indolent (slow-growing) non-Hodgkin lymphoma during pregnancy may be treated with watchful waiting until after they give birth. (See the Treatment Options for Indolent Non-Hodgkin Lymphoma section for more information.)

Aggressive Non-Hodgkin Lymphoma During Pregnancy

Treatment of aggressive non-Hodgkin lymphoma during pregnancy may include the following:

• Treatment given right away based on the type of non-Hodgkin lymphoma to increase the mother's chance of survival. Treatment may include combination chemotherapy and rituximab.
• Early delivery of the baby followed by treatment based on the type of non-Hodgkin lymphoma.
• If in the first trimester of pregnancy, medical oncologists may advise ending the pregnancy so that treatment may begin. Treatment depends on the type of non-Hodgkin lymphoma.

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