Small cell lymphocytic lymphoma

Contents

Types of B-cell Lymphoma

B-cell lymphomas make up most (about 85%) of the non-Hodgkin lymphomas (NHL) in the United States. These are types of lymphoma that affect B lymphocytes. The most common types of B-cell lymphomas are listed below.

Diffuse large B-cell lymphoma (DLBCL)

This is the most common type of NHL in the United States, accounting for about 1 out of every 3 lymphomas. The lymphoma cells look fairly large when seen with a microscope.

DLBCL can affect people of any age, but it occurs mostly in older people. The average age at the time of diagnosis is mid-60s. It usually starts as a quickly growing mass in a lymph node deep inside the body, such as in the chest or abdomen, or in a lymph node you can feel, such as in the neck or armpit. It can also start in other areas such as the intestines, bones, or even the brain or spinal cord.

DLBCL tends to be a fast-growing (aggressive) lymphoma, but it often responds well to treatment. Overall, about 3 out of 4 people will have no signs of disease after the initial treatment, and many are cured.

A subtype of DLBCL is primary mediastinal B-cell lymphoma. This type of lymphoma occurs mostly in young women. It starts in the mediastinum (the area in the middle of the chest behind the breastbone). It can grow quite large and can cause trouble breathing because it often presses on the windpipe (trachea) leading into the lungs. It can also block the superior vena cava (the large vein that returns blood to the heart from the arms and head), which can make the arms and face swell. This is a fast-growing lymphoma, but it usually responds well to treatment.

There are several other subtypes of DLBCL, but these are rare.

Follicular lymphoma

About 1 out of 5 lymphomas in the United States is a follicular lymphoma. This is usually a slow-growing (indolent) lymphoma, although some follicular lymphomas can grow quickly.

The average age for people with this lymphoma is about 60. It’s rare in very young people. Usually, this lymphoma occurs in many lymph node sites in the body, as well as in the bone marrow.

Follicular lymphomas often respond well to treatment, but they are hard to cure. These lymphomas may not need to be treated when they are first diagnosed. Instead, treatment may be delayed until the lymphoma starts causing problems. Over time, some follicular lymphomas can turn into a fast-growing diffuse large B-cell lymphoma.

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

CLL and SLL are closely related diseases. In fact, many doctors consider them different versions of the same disease. The same type of cancer cell (known as a small lymphocyte) is seen in both CLL and SLL. The only difference is where the cancer cells are found. In CLL, most of the cancer cells are in the blood and bone marrow. In SLL, the cancer cells are mainly in the lymph nodes and spleen.

Both CLL and SLL are usually slow-growing (indolent) diseases, although CLL, which is much more common, tends to grow more slowly. Treatment is the same for CLL and SLL. They are usually not curable with standard treatments, but many people can live a long time (even decades) with them. Sometimes, these can turn into a more aggressive (fast-growing) type of lymphoma over time.

For more information, see Chronic Lymphocytic Leukemia.

Mantle cell lymphoma (MCL)

About 5% of lymphomas are mantle cell lymphomas. MCL is much more common in men than in women, and it most often appears in people older than 60. When MCL is diagnosed, it is usually widespread in the lymph nodes, bone marrow, and often the spleen.

MCL can be challenging to treat. It tends to grow faster than indolent (slow-growing) lymphomas, but it doesn’t usually respond to treatment as well as aggressive (fast-growing) lymphomas. But newer treatments might offer a better chance for long-term survival for patients now being diagnosed.

Marginal zone lymphomas

Marginal zone lymphomas account for about 5% to 10% of lymphomas. They tend to be slow-growing (indolent). The cells in these lymphomas look small under the microscope. There are 3 main types of marginal zone lymphomas:

Extranodal marginal zone B-cell lymphoma, also known as mucosa-associated lymphoid tissue (MALT) lymphoma: This is the most common type of marginal zone lymphoma. It starts in places other than the lymph nodes (extranodal).

There are gastric and non-gastric MALT lymphomas. Gastric MALT lymphomas start in the stomach and are linked to infection by Helicobacter pylori (the bacteria that causes many stomach ulcers). MALT lymphoma might also start outside the stomach (non-gastric) in the lung, skin, thyroid, salivary glands, or tissues surrounding the eye. Usually the lymphoma stays in the area where it begins and is not widespread. Many of these other MALT lymphomas have also been linked to infections with bacteria (such as Chamydophila and Campylobacter) or viruses.

The average age of people with MALT lymphoma at the time of diagnosis is about 60. This lymphoma tends to grow slowly and is often curable if the amount of cancer is limited . Doctors often use antibiotics as the first treatment for MALT lymphoma of the stomach, because treating the Helicobacter pylori infection often cures the lymphoma.

Nodal marginal zone B-cell lymphoma: This is a rare disease. It starts and usually stays in the lymph nodes, although lymphoma cells can also sometimes be found in the bone marrow.

This lymphoma tends to be slow-growing (although not usually as slow as MALT lymphoma), and is treated similarly to follicular lymphoma.

Splenic marginal zone B-cell lymphoma: This is a rare lymphoma. Often the lymphoma is found mainly in the spleen, blood, and bone marrow.

It can cause fatigue and discomfort due to an enlarged spleen. Because the disease is slow-growing, it might not need to be treated unless the symptoms become troublesome. This type of lymphoma has been linked hepatitis C infection. Sometimes treating the hepatitis C virus can also treat this lymphoma.

Burkitt lymphoma

This fast-growing lymphoma is named after the doctor who first described this disease in African children and young adults. It makes up about 1% to 2% of all adult lymphomas. It is rare in adults, but is more common in children. It’s also much more common in males than in females.

The cells in Burkitt lymphoma are medium-sized. A similar kind of lymphoma, Burkitt-like lymphoma , has slightly larger cells but different chromosome changes.

Different varieties of this lymphoma are seen in different parts of the world:

  • In the African (or endemic) variety, Burkitt lymphoma often starts as a tumor of the jaw or other facial bones. Most cases of this type are linked to infection with the Epstein-Barr virus (EBV, which can also cause infectious mononucleosis or “mono”). This type of Burkitt lymphoma is rare in the United States.
  • In the type seen more often in the United States (nonendemic or sporadic), the lymphoma usually starts in the abdomen (belly), where it forms a large tumor. It can also start in the ovaries, testicles, or other organs, and can spread to the brain and spinal fluid. Some of these are linked to EBV infection.
  • Another type (immunodeficiency-associated) of Burkitt lymphoma is associated with immune system problems, such as in people with HIV or AIDS or who have had an organ transplant.

Burkitt lymphoma grows very quickly, so it needs to be treated right away. But more than half of patients can be cured by intensive chemotherapy.

Lymphoplasmacytic lymphoma (Waldenstrom macroglobulinemia)

This slow-growing lymphoma is not common, accounting for only 1% to 2% of lymphomas. The lymphoma cells are small and found mainly in the bone marrow, lymph nodes, and spleen. This lymphoma is discussed in detail in Waldenstrom Macroglobulinemia.

Hairy cell leukemia

Despite the name, hairy cell leukemia (HCL) is sometimes considered to be a type of lymphoma. It is rare – about 700 people in the United States are diagnosed with it each year. Men are much more likely to get HCL than women, and the average age at diagnosis is around 50.

The cells are small B lymphocytes with projections coming off them that give them a “hairy” appearance. They are typically found in the bone marrow, spleen, and in the blood.

Hairy cell leukemia is slow-growing, and some people may never need treatment. An enlarging spleen or low blood cell counts (due to cancer cells invading the bone marrow) are the usual reasons to begin treatment. If treatment is needed, it’s usually very effective.

Hairy cell leukemia is also talked about in Chronic Lymphocytic Leukemia.

Primary central nervous system (CNS) lymphoma

This lymphoma involves the brain or spinal cord (the central nervous system, or CNS). The lymphoma is also sometimes found in tissues around the spinal cord. Over time, it tends to become widespread in the central nervous system.

Primary CNS lymphoma is rare overall, but it’s more common in older people and in people with immune system problems, such as those who have had an organ transplant or who have AIDS. Most people develop headaches and confusion. They can also have vision problems; weakness or altered sensation in the face, arms, or legs; and in some cases, seizures.

The outlook for patients with primary CNS lymphoma has improved over the years mainly due to advances in treatment.

Primary intraocular lymphoma (lymphoma of the eye)

This is a rare type of lymphoma that starts in the eyeball and is often seen along with primary CNS lymphoma. It is the second most common cancer of the eye in adults, with ocular melanoma (eye melanoma) being the first. Most people with primary intraocular lymphoma are elderly or have immune system problems which may be due to AIDS or anti-rejection drugs after an organ or tissue transplant.

People may notice bulging of the eyeball without pain, vision loss, or a blurry vision. Many of the tests done to diagnose ocular melanoma are the same used to diagnose lymphoma of the eye.

The main treatment for lymphoma of the eye is external radiation therapy if the cancer is limited to the eye. Chemotherapy (chemo) or chemotherapy in combination with radiation may be used depending on the type of lymphoma and how far it has spread outside of the eye.

Small Lymphocytic Lymphoma (SLL): Treatment, Stages, Prognosis, and More

Treatment Options for Small Lymphocytic Lymphoma (SLL)

Treatment for SLL will depend on your symptoms, your age, the stage of the cancer, and your overall health.

Active Surveillance

If you have few or no symptoms, your doctor might decide not to treat the lymphoma right away. This is known as “active surveillance” or “watchful waiting.”

Studies have shown that people with less advanced disease who follow an active surveillance approach have similar outcomes as those who are treated early on.

With active surveillance, your physician will monitor the cancer and your overall health with regular checkups and tests. Treatment can be started if you develop symptoms or if tests show the cancer is progressing. (4)

Treatments

If your doctor recommends treatment, you may receive one medicine or a combination of different drugs. In some cases, these therapies may be given as part of a clinical trial. Or you might need a medical procedure to treat the cancer.

Options for SLL generally include:

  • Chemotherapy Chemotherapy medicines can be given orally or through an injection into a vein. Some chemotherapy drugs for SLL are: Cytoxan or Neosar (cyclophosphamide), Fludara (fludarabine), Leukeran (chlorambucil), Nipent (pentostatin), Treanda or Bendeka (bendamustine), and Revlimid (lenalidomide). These drugs are often used in combination with each other or with another type of medicine.
  • Monoclonal Antibodies These medicines use the body’s natural immune system to fight cancer. They’re typically administered by an injection and are often given along with chemotherapy or another type of drug. Monoclonal antibodies that are used for SLL may include: Rituxan (rituximab), Campath (alemtuzumab), Gazyva (obinutuzumab), and Arzerra (ofatumumab).
  • Targeted Treatments These therapies attack different targets on cancer cells. Imbruvica (Ibrutinib) and Zydelig (idelalisib) are examples of targeted treatments for SLL. Both of these medicines are pills that are taken by mouth and are sometimes used with other therapies.
  • Steroids Steroids may be used to destroy cancer cells or treat autoimmune issues in people with SLL or CLL.
  • Radiation Radiation therapy uses high energy rays to destroy cancer cells. It’s occasionally used in people with SLL.
  • Bone Marrow Transplant A bone marrow transplant, also called a “stem cell transplant,” may be an option for some people with SLL. It involves collecting stem cells from the blood or bone marrow of the patient or a matched donor. These cells are given back to the patient to restore damaged bone marrow after they receive high doses of chemotherapy, which wipe out the remaining bone marrow in their body. Because it can be hard on your body, a bone marrow transplant is often only performed on healthy, younger people.
  • Splenectomy Surgery to remove the spleen doesn’t treat SLL itself, but some people might need to have it if they develop complications. (9,10,11)

Complications

SLL can hinder your immune system and make it more difficult for you to fight infections. Sometimes the disease causes your immune system to attack itself, and you may develop life-threatening conditions.

Autoimmune hemolytic anemia (AIHA) happens when your immune system attacks your red blood cells. Immune thrombocytopenic purpura (ITP) occurs when your immune system targets the platelets in your blood. Both of these conditions may require immediate medical care.

It is also possible for SLL or CLL to transform into a more aggressive form of lymphoma. (9)

Clinical Trials

Researchers are investigating many new therapies for SLL. If the disease is very advanced or doesn’t respond to current treatments, your doctor might recommend that you enroll in a study.

Participating in a clinical trial may allow you to receive certain investigational therapies that aren’t yet available to the public.

You can find out more about clinical trials by visiting the Leukemia and Lymphoma Society’s website or ClinicalTrials.gov.

Remission, Relapse, and Refractory Disease

After treatment for SLL, you may go into remission, which means there are no signs of cancer in your body. During this time, your doctor will continue to monitor your health. You might need to have certain tests, such as blood draws or CT scans, to periodically check for cancer.

SLL often recurs, which means it returns after successful treatment. If this happens, you and your healthcare provider will come up with new treatment approaches.

The word “refractory” means that the lymphoma doesn’t respond to treatments or the response doesn’t last very long. Your doctor might recommend different medicines or a clinical trial if the cancer become refractory. (12,13)

What to know about non-Hodgkin lymphoma

There are many types of non-Hodgkin lymphoma. They fall into two main groups, based on whether the affected white blood cells are B cells or T cells.

Doctors also classify lymphomas based on how fast they grow. Any type can be slow-growing (indolent) or fast-growing (aggressive).

B cell types

According to the Cancer Support Community, around 85% of non-Hodgkin lymphoma cases in the U.S. start in B cells. Below are the two most common types.

Diffuse large B cell lymphoma

Around 1 in 3 cases of non-Hodgkin lymphoma are this type. It usually starts as a lump in a lymph node.

Sometimes, diffuse large B cell lymphoma starts in the intestine, bone, brain, or spinal cord. It grows quickly but usually responds well to treatment.

Follicular lymphoma

Almost 20% of lymphomas in the U.S. are this type, which starts in the lymph nodes and bone marrow.

Follicular lymphoma usually grows slowly and responds to treatment, but it is difficult to cure and may come back.

Less common types of B cell non-Hodgkin lymphoma include:

  • mucosa-associated lymphatic tissue lymphoma
  • small cell lymphocytic lymphoma, or chronic lymphocytic leukemia
  • intravascular large B cell lymphoma
  • mantle cell lymphoma
  • Burkitt’s lymphoma
  • hairy cell leukemia
  • primary central nervous system lymphoma
  • mediastinal (thymic) large B cell lymphoma
  • lymphoplasmacytic lymphoma, or Waldenstrom macroglobulinemia
  • nodal marginal zone B cell lymphoma
  • splenic marginal zone lymphoma
  • extranodal marginal zone B cell lymphoma
  • primary effusion lymphoma

T cell types

The Cancer Support Community report that T cell types account for fewer than 15% of all non-Hodgkin lymphoma cases in the U.S. Subtypes include:

  • Peripheral T cell lymphoma: Also known as generic T cell lymphoma, this is the most common type of T cell lymphoma, and there is a range of further subtypes.
  • Cutaneous T cell lymphoma: This type includes T cell lymphomas that primarily affect the skin, but they can also affect the blood, lymph nodes, and internal organs.

Other types of lymphoma that affect the T cells include:

  • anaplastic large cell lymphoma
  • angioimmunoblastic T cell lymphoma

Non-Hodgkin’s lymphoma: Small lymphocytic lymphoma

  • What is Small lymphocytic lymphoma
  • Statistics on Small lymphocytic lymphoma
  • Risk Factors for Small lymphocytic lymphoma
  • Progression of Small lymphocytic lymphoma
  • Symptoms of Small lymphocytic lymphoma
  • Clinical Examination of Small lymphocytic lymphoma
  • How is Small lymphocytic lymphoma Diagnosed?
  • Prognosis of Small lymphocytic lymphoma
  • How is Small lymphocytic lymphoma Treated?
  • Small lymphocytic lymphoma References

What is Small lymphocytic lymphoma

Lymphoma is divided into 2 broad groups: Hodgkin’s lymphoma and non-Hodgkin’s lymphoma. Non-Hodgkin’s lymphoma has many subtypes – and one of them is small lymphocytic lymphoma. Small lymphocytic lymphoma primary affects the B cells. It represents the tissue manifestation of chronic lymphocytic leukaemia (CLL).
Lymphoma means cancer of the lymphatic system. The lymphatic system is important to our immune system where it helps to combat infection. The lymphatic system consists of several organs, e.g. lymph nodes, spleen, thymus and bone marrow, where all these are connected by tiny vessels. Lymphatic fluid is the medium that circulates in these tiny vessels. Like blood, it has cells in them. These cells can be divided into 2 types: T cells and B cells.

Statistics on Small lymphocytic lymphoma

Small lymphocytic lymphoma is one of the subtypes of non-Hodgkin’s lymphoma. It represents 7% of all non-Hodgkin lymphoma. It is one of the common subtypes of indolent (or slow growing) lymphoma.
Racial variation does exist in small lymphocytic lymphoma. This disease is extremely rare in Asian countries like China and Japan. Predisposition to this disease includes caucasian population. Male to female ratio is about 1.7:1.
The median age of diagnosis is 65 years old.

Risk Factors for Small lymphocytic lymphoma

Age: middle-aged to elderly people
Gender: slight male predominance
Racial ethnicity: more common in caucasians, Western society

Progression of Small lymphocytic lymphoma

With respect to the natural history of lymphoma, small lymphocytic lymphoma is one of the indolent (or slow-growing) lymphomas. This means that it has good prognosis but may not be curable.
The course of small lymphocytic lymphoma is extremely variable depending on the clinical stage.
Generally the staging can be summarised as below:
Stage I – involvement of a single lymph node region or organ or site other than lymph nodes
Stage II – 2 or more lymph node regions involved on the same side of diaphragm
Stage III – 2 or more lymph node regions involved on both sides of diaphragm
Stage IV – one or more organs (e.g. bone marrow) involved
Each stage is subclassified into A and B (e.g. IIA), where B means presence of B symptoms (see below) while A means abscence of the following symptoms:

  • Unexplained fever higher than 38 Centigrade
  • Unexplained weight loss (defined as >10% of body weight in 6 months)
  • Night sweats

How is Small lymphocytic lymphoma Diagnosed?

The usual basic tests will be done, including those to look at the blood and other blood components. Other general tests will determine the function of the liver.

Prognosis of Small lymphocytic lymphoma

The prognosis is dependent on the clinical stage when the disease is
diagnosed. The later the stage, the worse the prognosis.
The following criteria are used to determine the prognosis of non-Hodgkin’s lymphoma:

  • Age >60
  • Blood lactate dehydrogenase (LDH) concentration greater than normal.
    Serum LDH is one of the many compounds found in the human blood system.

  • Patient is symptomatic and in bed <50% of the day or worse than this
  • Stage III or IV (see above for explanation on staging)
  • More than 1 involved site other than lymph nodesDepending on the amount of criteria met, the prognosis is as follows:
  • 0-1 76% of patients survive for 5 years
  • 2-3 51% of patients survive for 5 years
  • 4-5 38% of patients survive for 5 years

    How is Small lymphocytic lymphoma Treated?

    Because small lymphocytic lymphoma is an indolent (or slow growing) lymphoma and also it may not respond to treatment, ‘watchful waiting’ may be the choice. However, if symptoms develop, treatment may be started.
    Depending on the stage of disease and also the symptoms it produces, the following treatment modalities can be either given either alone or with combination.

  • Chemotherapy: this is using chemical (drugs) to kill the cancer cells.
  • Radiotherapy: this is using radiation to kill the cancerous cells.
    This is used when there is one or more lymph node regions affected in the same part of the body.
  • Small lymphocytic lymphoma References

    Chronic lymphocytic leukaemia . 2005 . Available from: URL: http://www.emedicine.com/med/topic370.htm
    Clinical and pathologic features of small lymphocytic, prolymphocytic, and lymphoplasmacytic lymphomas . 2005 . Available from: URL: http://uptodateonline.com/application/topic.asp?file=lymphoma/9728&type=A&selectedTitle=1~5
    Clinical Practice Guidelines for the Diagnosis and Management of Lymphoma . 2004 . Available from: URL: http://www.cancer.org.au/documents/chpt12_Lowgrade_lymphoma.pdf
    Small lymphocytic lymphoma . 2004 . Available from: URL: http://www.cancerbacup.org.uk/Cancertype/Lymphomanon-Hodgkins/TypesofNHL/Smalllymphocytic
    Warrell D et al. Oxford Textbook of Medicine. 4nd ed. Oxford; Oxford University Press; 2003.

Quick overview of CLL/SLL

This section is an overview of the information on this page. There is more detail in the sections below.

What is it?

CLL/SLL is a type of cancer that develops from B lymphocytes (white blood cells that fight infection). It is usually slow-growing and behaves like a chronic (long-term) condition; it needs treatment from time-to-time to keep it under control.

What are the symptoms and how is it diagnosed?

Most people have no symptoms when they are diagnosed, but can have high levels of lymphocytes (white blood cells) in their blood or sometimes enlarged lymph nodes (swollen glands). Some people never develop symptoms. Symptoms develop gradually and can include feeling generally unwell, with fatigue (extreme tiredness), fevers, night sweats, weight loss and frequent infections.

CLL is normally diagnosed by looking at abnormal cells from a blood test. People with SLL usually need a biopsy of an enlarged lymph node.

How is it treated?

Before starting treatment, you might be monitored (called active monitoring or watch and wait). You start treatment when your symptoms become troublesome. Some people never need treatment. The main treatment for CLL is chemo-immunotherapy (chemotherapy with antibody treatment). Targeted drugs are becoming very important for treating CLL, particularly for CLL that is difficult to treat or for CLL that has relapsed (come back) after chemo-immunotherapy. You have active monitoring between courses of treatment.

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What is CLL?

CLL and SLL are cancers of the lymphatic system. They can develop when lymphocytes (a type of white blood cell that fights infection) grow out of control. CLL has ‘leukaemia’ in its name because it affects the blood. SLL is another form of the same disease and it mainly affects the lymph nodes (glands), which is why it is called a ‘lymphoma’. Both forms of the disease are low-grade (slow-growing) and are often grouped as non-Hodgkin lymphomas. CLL and SLL are treated in the same way. On this page, the term ‘CLL’ is used to refer to both forms of the disease except where there are important differences.

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Who gets CLL and what causes it?

Around 3,500 to 4,000 people are diagnosed with CLL every year in the UK – that’s around 10 people every day. It affects nearly twice as many men as women. The risk of developing CLL increases with age, with an average age at diagnosis of 72 years. CLL is rare in young people.

In most cases, there is no known cause of CLL. People with a close relative (parent, brother, sister or child) with CLL are at an increased risk of developing CLL. However, the risk of developing CLL if you have a family member with the disease is still very small. Research has not identified any genes that are associated with developing CLL.

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Symptoms

The majority of people have no symptoms when they are diagnosed with CLL. In around 7 in 10 people, CLL is found by chance on a blood test done for another reason.

The abnormal cells in CLL are B cells that are immature (not fully developed) and don’t work properly. In the CLL form of the disease, the abnormal cells are found mainly in the blood. In the SLL form, they are found mainly in the lymph nodes or spleen and only at low levels in the blood.

As the abnormal cells build up, symptoms can develop. Any symptoms tend to be mild at first and gradually get worse as more abnormal cells build up. You might feel generally unwell, with symptoms like:

  • fatigue (extreme tiredness)
  • weight loss
  • fevers
  • night sweats.

As your immune system is affected, you might have frequent infections or find it difficult to shake off infections.

The abnormal cells can collect in your lymph nodes, causing them to swell. You might feel these as lumps. They can develop anywhere in your body but are most often found in your neck, armpit or groin. If abnormal cells build up in your spleen, you might feel pain or even a lump at the top-left of your abdomen (tummy).

CLL cells can build up in your bone marrow (the spongy centre of some of our bones where blood cells are made). This can cause low blood counts as the CLL cells take up the space of normal cells. You might develop:

  • anaemia (low red blood cells), which can cause tiredness and shortness of breath
  • thrombocytopenia (low platelets), which makes you more likely to bruise and bleed
  • neutropenia (low neutrophils – a type of white blood cell), which makes you more prone to infection.

Low blood counts in people with CLL can sometimes be due to an autoimmune reaction, where your body produces antibodies that destroy your blood cells, for example:

  • low red blood cells can be due to autoimmune anaemia
  • low platelets can be due to immune thrombocytopenic purpura (ITP).

Low blood counts due to autoimmune conditions need different treatment from low blood counts caused by too many abnormal cells in your bone marrow.

What is monoclonal B-lymphocytosis?

Some people have CLL-like cells at low levels in their blood but have normal blood counts and no other symptoms. This condition is called clinical monoclonal B-lymphocytosis (MBL). Many healthy older people (more than 1 in 10 people) have MBL and may not be aware of it. It does not usually cause any problems.

Most people with MBL do not go on to develop CLL, particularly if the abnormal cells are at a low level. However, evidence suggests that MBL develops first in all people who go on to develop CLL. Around 1–2 of every 100 people diagnosed with MBL develop CLL each year.

People with MBL who are at high risk of developing CLL usually have blood tests every so often to check if the level of abnormal cells is rising.

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Diagnosis and staging

CLL is usually first found in blood tests. If there are a large number of lymphocytes in your blood, CLL might be suspected. It is then diagnosed by looking at the lymphocytes in more detail and doing tests on them.

Tests on the abnormal lymphocytes also help your medical team to find out more about the CLL. For example, they can detect certain genetic mutations (changes) that make CLL more difficult to treat.

The SLL form is usually diagnosed by finding abnormal lymphocytes in a biopsy of a swollen lymph node.

When you have been diagnosed, you have other tests, for example:

  • more blood tests to find out about your general health
  • a physical examination to check for other signs of CLL such as enlarged lymph nodes or an enlarged spleen.

Some people have other tests, too, such as X-rays, a CT scan or bone marrow tests. These are done to find out if CLL is causing problems in certain parts of the body.

Although waiting for the results of your tests can be difficult, your doctor is collecting important information during this time. It is important that your doctor knows exactly how your CLL is affecting you so they can give you the most appropriate treatment.

What does ‘stage’ mean?

The tests you have are part of ‘staging’ – working out how widespread your CLL is and how it is affecting you. CLL is staged differently from other types of non-Hodgkin lymphoma because it is mostly found in the blood. The abnormal cells are therefore carried around the body in a different way to types of lymphoma that are mostly found in the lymph nodes. The most common staging system for CLL in the UK is the Binet staging system:

  • Stage A – you have fewer than three groups of swollen lymph nodes
  • Stage B – you have three or more groups of swollen lymph nodes
  • Stage C – you have anaemia (low red blood cells) or thrombocytopenia (low platelets) or both.

Another staging system, the Rai system, might be used. In this system, you are given a stage from 0 (the earliest stage) to 4 (the most advanced stage).

As SLL usually affects lymph nodes rather than blood, it is often staged the same way as non-Hodgkin lymphoma.

Staging is important because it helps your doctor plan the best treatment for you.

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Outlook

Most people with CLL are treated to keep the lymphoma under control, rather than to cure it. There are lots of good treatments for CLL. It can usually be controlled for many years with several courses of treatment.

Survival statistics can be confusing as they don’t tell you what your individual outlook is – they only tell you how a group of people with the same diagnosis did over a period of time in the past.

CLL usually grows very slowly and you might have many years between courses of treatment. However, some people have a faster-growing form that is likely to need more frequent treatment. Certain genetic mutations in the cells can make CLL more difficult to treat (‘high-risk’). For example, 17p or 11q deletions or TP53 mutations can affect how your CLL is treated.

In general, people with CLL at a lower stage have a better outlook than those with more advanced CLL.

Average expected survival is reported to be around 10 years but this varies a lot between individual people and depends on many factors including the stage of the CLL and how it behaves. The availability of newer targeted drugs is significantly improving the outlook for people with CLL. Some of these new treatments are very effective for people with high-risk genetic mutations and offer alternatives to standard chemo-immunotherapy (chemotherapy with antibody therapy), which does not work well for this type of CLL. As people with CLL generally live for many years, it takes a long time to find out how these newer treatments affect outcomes.

Your doctor is best placed to advise you on your outlook based on your individual circumstances. Your doctor can use the results of your tests and consider other factors, like your age, symptoms, and other conditions you might have to predict how likely you are to respond to a particular treatment. These factors are called ‘risk factors’.

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Treatment

CLL might not cause problems for many years. Some people never need treatment. Your doctor considers carefully whether you need treatment straightaway and what treatment is best for you. You are likely to need several courses of treatment during your illness. Most people have long periods of feeling well between courses of treatment.

Treatment aims to reduce your symptoms and keep the CLL under control for as long as possible with as few side effects as possible.

CLL is not causing problems for more than three-quarters of people when they are first diagnosed. If the CLL is not causing problems, you do not need treatment straightaway. You might be monitored regularly by your doctor until you need treatment (called active monitoring or watch and wait).

Research shows that there is no benefit to starting treatment before you need it. All treatment also carries a risk of causing side effects, so doctors often prefer to delay treatment for as long as possible.

What does active monitoring involve?

Your monitoring might be done at the hospital clinic or with your usual GP, depending on how your CLL behaves and your personal circumstances. You have blood tests and a check-up at each appointment. At first, the appointments may be every 3 months but the time between appointments might increase to once a year if you have early-stage CLL and stay well. The appointments allow your medical team to check for signs of the CLL getting worse. They also give you an opportunity to raise concerns and ask questions.

You are likely to have a physical examination and blood tests. Scans are not usually done unless there is a particular reason for them.

Some people go onto a self-management scheme. You are given information on what to look out for and how to look after yourself. You might have blood tests at your GP surgery.

If you are worried about your health at any time, contact your GP or medical team. They can reassure you or arrange an appointment for you to have a check-up.

You might have treatments to keep your symptoms under control while on active monitoring. For example, if you have autoimmune anaemia, you might be treated with steroids.

When does treatment start?

You usually start treatment for the CLL when it worsens, for example:

  • your symptoms (for example fevers, night sweats, fatigue or weight loss) become severe
  • the numbers of lymphocytes in your blood rise rapidly
  • your lymph nodes, spleen or liver become very enlarged
  • you develop low blood counts due to the abnormal lymphocytes collecting in your bone marrow
  • you have autoimmune anaemia or thrombocytopenia that is not responding to treatment.

There are different treatment options for CLL so your medical team consider several factors when they plan your treatment, including:

  • the stage of the CLL and whether it has high-risk genetic mutations
  • how the CLL is affecting you
  • your general health
  • your preferences.

What is the usual first treatment for CLL?

Most people have chemotherapy as a first treatment for CLL, usually with antibody treatment (for example rituximab) – this combination is sometimes called ‘chemo-immunotherapy’. If you are fit enough, the most common regimen (combination of drugs) is FCR (fludarabine, cyclophosphamide and rituximab).

If FCR is not suitable for you, other options include:

  • bendamustine chemotherapy, with or without rituximab,
  • chlorambucil chemotherapy tablets with one of the newer antibody treatments, obinutuzumab or ofatumumab.

These regimens both include intravenous treatments (given into a vein). For FCR and chlorambucil-based treatments, you also take some of the drugs orally, as tablets.

Note: after you have had treatment with fludarabine or bendamustine you must be given specially prepared ‘irradiated blood’ if you need to have blood transfusions in future. This is so that you don’t develop a rare but serious complication of blood transfusion called ‘transfusion-associated graft-versus-host disease’.

If your doctor thinks your CLL will respond to gentler treatment or you cannot have stronger treatment, they might recommend chlorambucil chemotherapy tablets alone.

Your doctor might suggest a different chemotherapy regimen or a targeted drug, possibly as part of a clinical trial. Find out more about clinical trials and search for a trial that might be suitable for you at Lymphoma TrialsLink.

I was treated as part of a clinical trial. The researchers won’t know if it was better than standard treatment for many years but I felt I was doing my bit for humanity by taking part. Michael, diagnosed with CLL at 63

If your CLL has features that mean it is unlikely to respond well to chemotherapy, for example high-risk genetic mutations, newer drugs can be very effective.

You also have treatments that help to control symptoms or side effects. These might include:

  • antibiotics, antifungal and antiviral drugs to prevent or treat infections
  • growth factor (G-CSF) injections to boost blood counts and help fight infection
  • immunoglobulin replacement therapy, where donor antibodies are given to help fight infection if your own antibody levels are low
  • red blood cell transfusions and/or platelet transfusions to boost blood counts
  • drug treatments for autoimmune low blood counts – steroids are usually given initially, but there are other treatment options.

Note: antibodies are naturally produced by your body to fight infection so the antibodies in immunoglobulin replacement therapy are not the same as man-made antibody treatments for CLL like rituximab.

Other treatments that are occasionally used for CLL include:

  • Radiotherapy, which might be used for early-stage SLL, where it can sometimes cure the lymphoma. Radiotherapy is not often used for CLL but might rarely be used to reduce large lymph nodes if other treatments are not suitable or did not work.
  • A splenectomy (surgery to remove the spleen) or splenic radiotherapy (radiotherapy to the spleen) might be used rarely if autoimmune complications of CLL are severe and do not respond to other treatments. This treatment doesn’t usually treat the CLL itself.
  • Steroids, which are often used to treat side effects but can also help to control the CLL.

Rarely, if you respond well to your first treatment, your doctor might suggest an allogeneic stem cell transplant, which could offer a longer-lasting remission. This is an intensive form of treatment and is only suitable for people who are fit enough.

All treatment has a risk of side effects (unwanted effects). Your medical team can give you more information about the typical side effects of the treatment they recommend for you.

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Follow-up

Most people go back onto active monitoring after treatment if the CLL is under control.

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Relapsed and refractory CLL

Remissions (time when the CLL is under control) are increasing in length with new and more effective treatments for CLL. However, CLL usually flares up again after a period of remission. Most people need several courses of treatment during their illness.

If your lymphoma doesn’t respond well to your first treatment, it is called ‘refractory’ and you might need a different or stronger treatment.

When you need more treatment, your doctor considers the same factors as before but also takes into account:

  • what treatment you had before
  • how long your remission was after your previous treatment
  • how your previous treatment affected you.

You might have the same treatment that you had previously if you coped well with it and had a good response to it. Your doctor might suggest a different treatment, particularly if your CLL relapsed quickly after your last treatment. For example, you might have a different chemo-immunotherapy regimen.

Newer targeted treatments might be available for relapsed or refractory CLL.

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Research and targeted treatments

Newer targeted treatments are often available first for people with relapsed and refractory lymphoma. For CLL, targeted treatments are also beginning to be used as a first treatment, particularly for people with high-risk genetic mutations.

There are several targeted treatments already approved for CLL and many clinical trials testing new treatments for this type of lymphoma. Our newer drugs page has the latest information on drugs available for CLL and other types of lymphoma. You can also search our clinical trials information service, Lymphoma TrialsLink, to find clinical trials currently open in the UK for people with CLL.

At the time of writing, the following targeted treatments are approved for some people with CLL and might be available on the NHS in some parts of the UK although the funding available varies. Your medical team can give you more information about treatments that might be suitable for you.

Ibrutinib

Ibrutinib is a cell signal blocker. It blocks signals that B cells send to help them stay alive and divide.

  • It is given on its own as a first-line treatment for people with high-risk genetic mutations.
  • For relapsed or refractory CLL, it is usually given on its own, but within clinical trials it is being combined with other drugs including rituximab and venetoclax.

Idelalisib

Idelalisib is also a cell signal blocker. It is approved for:

  • first-line treatment of people with high-risk genetic mutations
  • in combination with antibody treatment for people with relapsed or refractory CLL.

Obinutuzumab

Obinutuzumab is a newer antibody that attaches to the same target as rituximab does, a protein called ‘CD20’. It is approved for use with chlorambucil as a first treatment for people who can’t have fludarabine.

Ofatumumab

Ofatumumab is also a newer antibody to CD20. It is approved:

  • with chlorambucil or bendamustine chemotherapy as a first treatment for people who can’t have fludarabine.
  • for people with CLL who have had other treatments.

Venetoclax

Venetoclax blocks proteins that help lymphoma cells survive. This can make the lymphoma cells die.

  • It can be given with rituximab for people with CLL that has not responded (refractory) or has come back (relapsed) after previous treatment.
  • It can be given on its own for people with high-risk genetic mutations who cannot have a cell signal blocker or have not responded to a cell signal blocker, or to people who have not responded to previous therapy with a cell signal blocker and chemo-immunotherapy.

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Transformation

Rarely, CLL transforms (changes) into a more aggressive type of lymphoma, usually diffuse large B-cell lymphoma (DLBCL). This is known as ‘Richter syndrome’. Evidence suggests up to 1 in every 100 people with CLL develop Richter syndrome each year.

As part of your follow-up, your medical team check for signs of transformation. These include:

  • fast growing lymph nodes or masses in your body
  • a change in your symptoms, for example B symptoms (weight loss, night sweats, fevers)
  • an increase in certain chemicals measured in blood tests, for example lactate dehydrogenase (LDH) or calcium.

Tests such as a biopsy and a PET or CT scan might be done if your doctor suspects your CLL has transformed.

Transformed CLL can be difficult to treat. It does not usually respond well to treatment. Many people with transformed CLL are older and have had several previous courses of treatment so might not be fit enough for intensive treatment. The most likely treatment is chemotherapy, possibly followed by a stem cell transplant if you are fit enough. If you are not fit enough for chemotherapy, you might be able to enter a clinical trial or you might consider palliative care, where you are given treatment to control your symptoms.

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Living with CLL

Most people live with CLL for many years. For some people, having CLL does not affect their life expectancy, but it can affect their quality of life. Issues such as chronic fatigue and recurrent infections are more common in people with CLL than in the general population.

It is important that you discuss these issues with your medical team. Although fatigue can be very challenging, there are things you can do to help manage it. Seek medical advice promptly if you have any symptoms of infection as it is important that you get early treatment with antibiotics and anti-viral drugs.

Some people have immunoglobulin replacement therapy, where you have infusions (drips) that include donor antibodies to reduce the number of infections you have. People with CLL and MBL should have vaccinations against influenza (flu) and pneumonia. You should not have live vaccines, such as the shingles / zoster vaccine as this can cause problems for people with a weakened immune system.

We have more information covering many aspects of living with a chronic condition like CLL.

We also offer a range of support services to help you live your life with CLL. We also have a Live your Life programme of free support, events and activities for people with a lymphoma diagnosis and their family, carers or friends.

HealthTalk have a range of videos of people talking about their experiences of CLL that you might find useful.

Our list of organisations that offer support and information for people with lymphoma might also be useful. The following organisations offer support and information that is particularly relevant for people with CLL:

  • The CLL Support Association
  • Leukaemia Care

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Lymphocytic Lymphoma

Small Lymphocytic Lymphoma

The WHO Classification defines small lymphocytic lymphoma as the nodal equivalent of classic B-cell chronic lymphocytic leukemia. The two diseases are considered different stages of the same disease, and the distinction between the two is arbitrary. One group recommended the designation chronic lymphocytic leukemia if patients have more than 5000/mm3 circulating lymphocytes and more than 30% lymphocytes in the marrow, but this term is not universally accepted.327 The Working Formulation’s low-grade category of small lymphocytic lymphoma also comprised several other clinicopathologic entities, including marginal zone B-cell lymphoma (particularly the extranodal variants), lymphoplasmacytic lymphoma/immunocytoma, and some cases of mantle cell lymphoma, which are now considered separate categories of B-cell lymphoma in the WHO Classification. Small lymphocytic lymphoma is seen almost exclusively in adults older than 40 years, with a median age of approximately 60 years.328-330 Most patients present with generalized lymphadenopathy. Many of these patients have or develop peripheral blood involvement during their disease course. Pathologic stage IV disease is seen in approximately 80% of patients at presentation, usually because of bone marrow involvement but also frequent liver and spleen involvement. The clinical course is indolent; spontaneous regression occurs in 15% of untreated patients, progression is slow, and numerous relapses occur over time seemingly independent of treatment.291 Ten percent to 20% of patients undergo histologic transformation to large cell lymphoma (Richter’s syndrome).291,331 As previously discussed, rare cases may undergo transformation to lymphoma with a Hodgkin’s-like histologic appearance or even true Hodgkin’s lymphoma.284,332 Treatments may include combinations of purine analogs, such as fludarabine or 2-chlorodeoxyadenosine, with alkylating agents. Two monoclonal antibodies, rituximab and anti-CD52, have also emerged as therapies.333

The diagnosis of small lymphocytic lymphoma is often made on low-magnification microscopic examination by appreciating nearly diffuse nodal effacement, perinodal adipose tissue infiltration, and pale proliferation centers (also known as pseudofollicles).334,335 The mitotic rate is generally low, but higher numbers may be found in the proliferation centers. At high magnification, the predominant cell type is a small lymphoid cell with condensed chromatin (Fig. 41-47). The cells are usually round but may exhibit a mild degree of nuclear irregularity. Nucleoli are generally small but may be moderately sized in some cases. Cytoplasm is generally scant. In some cases, the small lymphoid cells have plasmacytoid features. In addition to the small cells, one also always sees a population of larger cells. These cells may be medium sized, termed prolymphocytes or paraimmunoblasts (Fig. 41-48), or the cells may be large, termed immunoblasts. Both larger cell types have round nuclei with a vesicular chromatin pattern and medium to large nucleoli. The aggregation of these large cells gives rise to the proliferation centers appreciated at low magnification. Other cell types, including eosinophils, neutrophils, and histiocytes, are not found in any appreciable number. The proliferation centers are particularly identified in cases associated with peripheral blood lymphocytosis.335 Rarely, paraimmunoblasts may predominate; this disorder is then termed the paraimmunoblastic variant of small lymphocytic lymphoma.336 Patients with this variant have a worse prognosis than do patients with other types of small lymphocytic lymphoma, but it is still better than for de novo diffuse large cell lymphoma. However, when immunoblasts predominate and form sheets, this indicates transformation to a higher-grade lymphoma, and the prognosis becomes significantly worse. Fine-needle aspiration biopsy smears of small lymphocytic lymphoma show a preponderance of small lymphoid cells with round, regular nuclear membranes and clumped chromatin, with occasional admixed cells of similar size with an open chromatin pattern and a prominent nucleolus, representing prolymphocytes.

Figure 41-47. Small lymphocytic lymphoma. Most cells are small with round nuclear contours and mature chromatin, but larger cells with prominent nucleoli evenly distributed throughout the nodal parenchyma are also present.

Figure 41-48 ▪. Small lymphocytic lymphoma, paraimmunoblasts. Cases of small lymphocytic lymphoma always have admixed paraimmunoblasts, whether in clusters or as individual cells. The paraimmunoblasts have slightly more open chromatin and small nucleoli. The nuclei are still round and regular.

Small lymphocytic lymphomas are B-lineage neoplasms. They express the B-cell markers CD20 and CD79a in paraffin sections, but the reactivity for CD20 is usually weak.17,32,337,338 Immunoglobulin expression with light-chain restriction is seen in virtually all cases by flow cytometry, but the level of immunoglobulin expression is typically low.339,340 Both µ and δ heavy chains are characteristically present. Results of immunoglobulin studies in paraffin sections are usually negative unless the cells exhibit some plasmacytoid features, but the cells usually have faint immunoglobulin expression in frozen sections.341 Aberrant expression of the paraffin T/myeloid marker CD43 is found in approximately 80% of cases.342 Aberrant expression of CD5 is found in approximately 90% of cases by flow cytometry, frozen section immunohistochemistry, and paraffin immunohistochemistry.343 In contrast to mantle cell lymphoma, results of testing for CD23 are usually positive, and in contrast to follicular lymphoma, results of testing for CD10 are usually negative.82,312,344 CD22 antigen is weakly expressed on chronic lymphocytic leukemia/small lymphocytic lymphoma (≥90%).345 The most common cytogenetic abnormalities in small lymphocytic lymphoma are probably deletions of chromosome bands 13q14 (50% of cases) and 11q (20%).330,346 Deletions at 6p21 or 17p13 (p53 locus) occur in approximately 5% and 10% of cases, respectively.346 Translocations involving 17p may be associated with inferior survival time and may predict poor response to rituximab therapy.347 Trisomy of chromosome 12 is found in approximately one third of cases and is more commonly associated with cases with atypical features or undergoing transformation to a higher-grade process.330,346 Monoclonal rearrangement of the immunoglobulin heavy-chain and light-chain genes is seen in virtually all cases. The mutational status of the immunoglobulin VH genes appears to define two prognostically distinct type of small lymphocytic lymphoma/chronic lymphocytic leukemia: one group is consistent with naïve B cells, whereas the other group appears to be derived from postgerminal center B cells.348,349

Adverse prognostic factors include diffuse bone marrow involvement, atypical peripheral blood morphology with increased numbers of prolymphocytes, high proliferation, poor-risk cytogenetics including 17p deletions, 11q deletions, and complex karyotypes, mutated IGH genes, and expression of CD38. ZAP-70 expression is a useful surrogate for unmutated IGH status and can be easily measured by flow cytometry or paraffin immunohistochemistry.350

The differential diagnosis of small lymphocytic lymphoma includes reactive lymphoid proliferations, follicular lymphoma, and other small cell B-lineage lymphomas. By morphology, small lymphocytic lymphoma can usually be distinguished from reactive lymphoid proliferations; small lymphocytic lymphoma has a somewhat monotonous cellular population, with lack of normal architectural compartmentalization. Results of paraffin section immunohistochemical studies of small lymphocytic lymphoma show a diffuse B-cell infiltrate, most often with aberrant CD43 and CD5 coexpression; in frozen section immunohistochemical studies, light-chain restriction is usually seen. These findings are in contrast to a well-compartmentalized pattern in reactive infiltrates. Results of flow cytometric studies also show a monotypic population in small lymphocytic lymphoma as well as characteristic dim CD20 and surface immunoglobulin positivity, reactivity of CD5 and CD23, and lack of FMC7 expression.339 Prominent proliferation centers may be mistaken for the neoplastic follicles of follicular lymphoma. However, the proliferation centers are always more poorly defined than neoplastic follicles and lack small cleaved cells. Immunohistochemical analysis may show scattered follicular dendritic cells, but the network is never as well developed as in follicular lymphoma. Results of CD10 staining are usually positive in follicular lymphoma and usually negative in small lymphocytic lymphoma, which may be difficult to distinguish from other diffuse small cell B-lineage lymphomas. The presence of proliferation centers or CD23 positivity favors small lymphocytic lymphoma over the other neoplasms. The presence of scattered larger cells also distinguishes small lymphocytic lymphoma from mantle cell lymphoma, which has a monotonous small cell population, whereas the identification of t(11;14) favors mantle cell lymphoma. In addition, results of flow cytometric study of mantle cell lymphoma show FMC7 positivity, bright CD20 and surface immunoglobulin positivity, and no expression of CD23.339

The cells of marginal zone B-cell lymphoma generally have more abundant cytoplasm than do the cells of small lymphocytic lymphoma and commonly have extranodal sites of involvement. In addition, marginal zone B-cell lymphomas have aberrant CD43 expression in only approximately 30% of cases and usually do not coexpress CD5. Although small lymphocytic lymphoma may show mild plasmacytoid features, marked plasmacytic differentiation with Dutcher bodies and Russell bodies is more commonly seen in lymphoplasmacytic lymphoma.330 Clinically, patients with lymphoplasmacytic lymphoma often have large M protein spikes or even symptoms of Waldenström’s macroglobulinemia. A rare signet ring cell variant of small lymphocytic lymphoma may be confused with metastatic carcinoma, but immunohistochemical study helps to differentiate the lymphoma from the carcinoma.351 The diffuse nature and CD5 and CD43 coexpression also distinguish this rare variant from the signet ring cell variant of follicular lymphoma.

What Is B-Cell Lymphoma?

Certain types of lymphoma that are asymptomatic and indolent don’t necessarily require treatment. Your doctor may recommend what is known as “watchful waiting.” That means you’ll follow up every few months to make sure the cancer isn’t advancing. In some cases, this can continue for years.

Treatment can start when symptoms appear or if there are signs of disease progression. B-cell lymphoma often involves a combination of treatments, which may change over time.

Radiation

Using high-powered energy beams, radiation therapy is used to kill cancer cells and shrink tumors. It requires lying very still on a table while the beams are directed to a precise point on your body.

For slow-growing, localized lymphoma, radiation therapy may be all you need.

Side effects can include fatigue and skin irritation.

Chemotherapy

Chemotherapy is a systemic treatment that can be given orally or intravenously. Some aggressive B-cell lymphomas can be cured with chemotherapy, especially in early stage disease.

DLBCL is a fast-growing type that can be treated with a chemotherapy regimen called CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone). When given along with the monoclonal antibody rituximab (Rituxan), it’s called R-CHOP. It’s usually given in cycles several weeks apart. It’s hard on the heart, so it’s not an option if you have preexisting heart problems.

Side effects of chemotherapy may include nausea, fatigue, and hair loss.

Immune therapy

Biologic drugs help your immune system fight cancer. Rituximab targets proteins on the surface of B-cells, making it easier for the immune system to identify and destroy them. By decreasing the number of cancerous and healthy B-cells, the drug prompts your body to produce new healthy B-cells. This makes it less likely that cancer will recur.

Radioimmunotherapy medicines, such as ibritumomab tiuxetan (Zevalin), are made of monoclonal antibodies that carry radioactive isotopes. The drug helps antibodies attach to the cancer cells for direct delivery of radiation.

Side effects of immune therapy can include low white blood cell counts, fatigue, and infections.

Stem cell transplant

A stem cell transplant involves replacing your bone marrow with marrow from a healthy donor. First, you’ll need high-dose chemotherapy or radiation to suppress your immune system, destroy cancer cells, and make room for the new marrow. To be eligible, you must be healthy enough to withstand this treatment.

Side effects can include infections, anemia, and rejection of the new bone marrow.

Treating B-Cell Non-Hodgkin Lymphoma

Non-Hodgkin lymphoma (NHL) is generally divided into main 2 types, based on whether it starts in B lymphocytes (B cells) or T lymphocytes (T cells). There are many different types of B-cell lymphomas. Treatment usually depends both on the type of lymphoma and the stage (extent) of the disease, but many other factors can be important as well.

Diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) tends to grow quickly. Most often, the treatment is chemotherapy (chemo), usually with a regimen of 4 drugs known as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), plus the monoclonal antibody rituximab (Rituxan). This regimen, known as R-CHOP, is most often given in cycles 3 weeks apart. Because this regimen contains the drug doxorubicin, which can damage the heart, it may not be suitable for patients with heart problems, so other chemo regimens may be used instead.

Stage I or II

For DLBCL that is only in 1 or 2 lymph node groups on the same side of the diaphragm (the thin muscle that separates the chest from the abdomen), R-CHOP is often given for 3 to 6 cycles, which might be followed by radiation therapy to the affected lymph node areas.

Stage III or IV

Most doctors will give 6 cycles of R-CHOP as first-line treatment. After several cycles, doctors may get imaging tests such as a PET/CT scan to see how well treatment is working. People who have a higher risk of the lymphoma coming back later in the tissues around the brain and spinal cord may be treated with chemo injected into the spinal fluid (called intrathecal chemotherapy). Another option is to give high doses of methotrexate intravenously. (This drug can pass into the spinal fluid.)

For younger patients with a higher risk of the lymphoma coming back based on the International Prognostic Index (IPI) score, high-dose chemo followed by a stem cell transplant might be an option. But it’s not yet clear if transplants are better as the initial treatment. Most doctors feel that if a transplant is done as part of the first treatment, it should be done in a clinical trial.

If the lymphoma doesn’t go away completely with treatment or if it recurs (comes back) after treatment, doctors will usually suggest another chemo regimen. Several different regimens can be used, and they may or may not include rituximab. If the lymphoma shrinks with this treatment, it might be followed by a stem cell transplant if possible, as it offers the best chance of curing the lymphoma. Stem cell transplants are not effective unless the lymphoma responds to chemo. Unfortunately, not everyone is healthy enough for a stem cell transplant.

CAR T cell therapies or a monoclonal antibody that targets CD79b can be considered if 2 or more treatments have been tried. Clinical trials of new treatments may be another good option for some people.

DLBCL can be cured in about half of all patients, but the stage of the disease and the IPI score can have a large effect on this. Patients with lower stages have better survival rates, as do patients with lower IPI scores.

Primary mediastinal B-cell lymphoma

This lymphoma, which starts in the space between the lungs (the mediastinum), is treated like early stage diffuse large B-cell lymphoma. A common treatment is 6 courses of CHOP chemo plus rituximab (R-CHOP). This may be followed by radiation to the mediastinum. Often a PET/CT scan is done after the chemo to see if there’s any lymphoma remaining in the chest. If no active lymphoma is seen on the PET/CT, the patient may be observed without further treatment. If the PET/CT scan is positive (shows possible active lymphoma), radiation may be needed. Sometimes, the doctor will order a biopsy of the chest tumor to confirm that lymphoma is still present before starting radiation.

Another treatment option is 6 cycles of dose-adjusted etoposide, doxorubicin and cyclophosphamide with vincristine, prednisone and rituximab (DA-EPOCH-R) which typically does not require any radiation.

If the primary mediastinal B cell lymphoma does comes back or does not respond to chemo, immunotherapy with the drug pembrolizumab may be an option.

This type of lymphoma often grows slowly and responds well to treatment, but it is very hard to cure. It often comes back after treatment, although it can take many years to do so. It’s not always clear if the lymphoma needs to be treated right away, especially if the lymphoma isn’t causing problems other than mildly swollen lymph nodes. Some people may never need treatment at all. For those who do, sometimes it might be years before treatment is needed.

Stage I and early-stage II

If treatment is needed for follicular lymphoma that is only in 1 lymph node group or in 2 nearby groups that are both above or below the diaphragm (the thin muscle separating the chest from the abdomen), the preferred treatment is radiation therapy to the lymph node areas affected by lymphoma (called involved site radiation). Other choices include treatment with chemo plus a monoclonal antibody (rituximab or obinutuzumab ), or rituximab alone, which might be followed by radiation therapy.

Stages III, IV, and most stage II bulky lymphomas

If treatment is needed, the most common option is a monoclonal antibody (rituximab or obinutuzumab) combined with chemo. The chemo can be a single drug (such as bendamustine) or a combination of drugs, such as the CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or CVP (cyclophosphamide, vincristine, prednisone) regimens.

If some lymph nodes are very large from the lymphoma, radiation may be used to reduce symptoms. This is most often used for patients who are too sick to be treated with chemo.

The radioactive monoclonal antibody ibritumomab (Zevalin) is also an option for initial treatment, although this is more often used as a second-line treatment.

For patients who may not be able to tolerate more intensive chemo regimens, rituximab alone, rituximab with milder chemo drugs (such as chlorambucil or cyclophosphamide), or rituximab with lenalidomide may be good options .

If the lymphoma shrinks or goes away with the initial treatment, doctors may advise either close follow-up or further treatment. This might include continuing the monoclonal antibody (rituximab or obinutuzumab) for up to 2 years, or treatment with ibritumomab. Further treatment may lower the chance that the lymphoma will come back later and may help some patients live longer, but it can also have side effects.

If follicular lymphoma doesn’t respond to the initial treatment or if it comes back later, it may be treated with different chemo drugs, targeted drugs, immunotherapy, or some combination of these. If the lymphoma responds to this treatment, a stem cell transplant may be an option.

A small portion of follicular lymphomas, known as grade 3B lymphomas, tend to grow quickly, more like diffuse large B-cell lymphoma (DLBCL). Some follicular lymphomas can also change (transform) into or return as DLBCL. For these lymphomas, your doctor will review which treatments you may have already had to decide which is the next best treatment option.

Small lymphocytic lymphoma (and chronic lymphocytic leukemia)

Small lymphocytic lymphoma (SLL) and chronic lymphocytic leukemia (CLL) are considered different versions of the same disease. The main difference is where the cancer cells are (the blood and bone marrow for CLL, and the lymph nodes and spleen for SLL). CLL and SLL tend to grow slowly, but are very hard to cure.

Treatment for SLL is similar to that of CLL, which is described in detail in Treating Chronic Lymphocytic Leukemia.

If the lymphoma isn’t growing quickly or causing any problems, it can be watched closely without treatment for a time. If treatment is needed, it depends on the stage.

When the lymphoma is only in one lymph node or lymph node area (stage I), it may be treated with radiation therapy alone.

For more advanced disease, the treatment is often the same as what is used for CLL. (See Treating Chronic Lymphocytic Leukemia.) Chemo, with or without rituximab or obinutuzumab (Gazyva) is one option for first-line treatment. Chlorambucil, fludarabine, or bendamustine are some of the chemo drugs that are used. The targeted drug ibrutinib (Imbruvica) is another option, as is rituximab alone (without chemo). Which treatment is used depends on a person’s age and health, as well as on whether the cancer cells have certain chromosome changes.

If the lymphoma doesn’t respond or comes back after initial treatment, different chemo drugs, targeted drugs, and/or other monoclonal antibodies may be used as second-line treatment.

Mantle cell lymphoma

This type of lymphoma has often spread widely when it’s first found. Although it doesn’t usually grow as quickly as some other fast-growing lymphomas, it often doesn’t respond as well to treatment, either. Because current treatments for this type of lymphoma aren’t likely to cure it, patients might want to consider taking part in a clinical trial.

If the lymphoma has only spread to 1 lymph node group or to 2 nearby groups on the same side of the diaphragm (stage I and some stage II), which is rare, it can sometimes be treated with radiation therapy. Another option is to treat with chemo plus rituximab.

Mantle cell lymphomas that have spread more widely when they are first diagnosed are treated with chemo plus rituximab.

When possible, the chemo treatment is intense, using regimens such as:

  • Hyper-CVAD: cyclophosphamide, vincristine, doxorubicin (Adriamycin), and dexamethasone, alternating with high-dose methotrexate plus cytarabine)
  • “Dose-intensified” R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), alternating with rituximab and cytarabine
  • RDHAP (Rituximab, dexamethasone, cytarabine, cisplatin)

If the lymphoma responds well to these initial treatments, a stem cell transplant may be a good option, followed by rituximab for 3 years.

Less intense chemo regimens, such as bendamustine with rituximab, may be used for people who are older or who have other health issues.

For mantle cell lymphomas that don’t respond or that come back after initial treatment, chemo with drugs such as bendamustine, bortezomib (Velcade), cladribine, fludarabine, or lenalidomide (Revlimid) may be used, sometimes along with other chemo drugs or with rituximab. Another option includes the use of a targeted drug, such as ibrutinib (Imbruvica), acalabrutinib (Calquence), or zanubrutinib (Brukinsa). Other targeted drugs such as venetoclax (Venclexta) and idelalisib (Zydelig) have also shown promising results in some early studies. Still, because second-line treatment is not always helpful, patients might want to consider entering a clinical trial.

Extranodal marginal zone B-cell lymphoma – mucosa-associated lymphoid tissue (MALT) lymphoma

Gastric (stomach) MALT lymphoma, the most common type, often occurs as a result of a chronic infection with the bacterium H. pylori, and it often responds to treatment of the infection. Because of this, gastric lymphomas are treated differently from other lymphomas in this group.

Stages I and II gastric lymphoma in people who test positive for H. pylori

Early-stage gastric MALT lymphomas are treated with antibiotics combined with drugs that block acid secretion by the stomach (called proton pump inhibitors). Usually the drugs are given for 10 to 14 days. This may be repeated after a couple of weeks. Examination of the stomach lining using upper endoscopy (where a flexible tube with a viewing lens is passed down the throat and into the stomach) is then repeated at certain intervals to see if the H. pylori is gone and if the lymphoma has shrunk. About 2 out of 3 of these lymphomas go away completely with antibiotic treatment, but it can sometimes take several months to be effective. In cases where symptoms need to be relieved before the antibiotics take effect or where antibiotics don’t shrink the lymphoma, radiation therapy to the area is often the preferred treatment. The monoclonal antibody rituximab may be another option.

Stages I and II gastric lymphoma in people who test negative for H. pylori

For these early-stage gastric MALT lymphomas, treatment is usually either radiation therapy to the stomach or rituximab.

Stage III or IV gastric lymphoma

For more advanced gastric MALT lymphomas, which are rare, treatment is often similar to that for follicular lymphoma (see above). Lymphomas that are not growing quickly may be watched and not treated right away. If the lymphoma is large, is causing symptoms, or is growing, it can be treated with radiation therapy to the stomach, rituximab, chemo, chemo plus rituximab, or the targeted drug ibrutinib (Imbruvica). The chemo drugs used are the same as those used for follicular lymphoma, and may include single agents such as chlorambucil or fludarabine or combinations such as CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or CVP (cyclophosphamide, vincristine, prednisone).

Non-gastric MALT lymphoma

For MALT lymphomas that start in sites other than the stomach (non-gastric lymphomas), treatment depends on the location of the lymphoma and how much it has spread. Early-stage lymphomas can often be treated with radiation to the area containing the lymphoma. In certain sites (such as the lungs, breast, or thyroid), surgery may be an option. For more advanced disease (stage III or IV), treatment is generally the same as for stage III and IV gastric MALT lymphoma and follicular lymphoma (see above).

Nodal marginal zone B-cell lymphoma

This rare type of lymphoma is generally slow growing (indolent), and it often doesn’t need to be treated right away. If it does need treatment, it is usually treated the same way as follicular lymphoma (which also tends to grow slowly).

If treatment is needed for lymphoma that is only in 1 lymph node group or in 2 nearby groups on the same side of the diaphragm (the thin muscle separating the chest from the abdomen), the preferred treatment is radiation therapy to the lymph node areas affected by lymphoma (called involved site radiation). Other choices include treatment with rituximab (Rituxan), chemo, or both, which might be followed by radiation therapy.

If treatment is needed, the most common option is rituximab combined with chemo. The chemo can be a single chemo drug (such as bendamustine or fludarabine) or a combination of drugs, such as the CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or CVP (cyclophosphamide, vincristine, prednisone) regimens. If the lymphoma shrinks, a total of 6 cycles of chemo plus rituximab is usually given.

Other options for initial treatment include rituximab alone or chemo alone (either one or several drugs). If some lymph nodes are very large from the lymphoma, radiation may be used to reduce symptoms. This is most often used for patients who are too sick to be treated with chemo.

The radioactive monoclonal antibody ibritumomab tiuxetan (Zevalin) is also an option for initial treatment, although this is more often used as a second treatment.

For patients who may not be able to tolerate more intensive (stronger) chemo regimens, rituximab alone, milder chemo drugs (such as chlorambucil or cyclophosphamide), or both may be good options.

If the lymphoma shrinks or goes away with the initial treatment, doctors may advise either close follow-up or further treatment. This might include either rituximab for up to 2 years or treatment with ibritumomab tiuxetan. Further treatment may lower the chance that the lymphoma will come back later and may help some patients live longer, but it can also have side effects.

If the lymphoma doesn’t respond to the initial treatment or if it comes back later, it may be treated with different chemo drugs, immunotherapy, targeted drugs, or some combination of these. If the lymphoma responds to this treatment, a stem cell transplant may be an option.

Nodal marginal zone B-cell lymphoma can also change into a fast-growing diffuse large B-cell lymphoma (DLBCL), which would require more aggressive chemotherapy (see above).

Splenic marginal zone B-cell lymphoma

This is typically a slow-growing lymphoma. If it is not causing symptoms, it is often watched closely without treating it right away.

About 1 in 3 people with this type of lymphoma have chronic hepatitis C virus (HCV) infection. Treating the infection with anti-viral drugs can often cause these lymphomas to go into remission.

If that doesn’t work, or if a person isn’t infected with HCV, surgery to remove the spleen can sometimes lead to a long-term remission. This can be very helpful in relieving symptoms if the spleen is enlarged. Treatment with rituximab may be another option.

If the disease is more advanced or progresses, it’s usually treated with chemo with or without rituximab (similar to what is used for advanced stage follicular lymphoma, which is described above). Another option might be the targeted drug ibrutinib (Imbruvica) or rituximab with lenalidomide.

Sometimes this lymphoma can transform into an aggressive large-cell lymphoma, which then requires more intensive chemo.

This is a very fast-growing lymphoma that is similar to a type of acute lymphocytic leukemia. It is usually treated in the hospital with intensive chemo, which usually includes at least 5 chemo drugs. Rituximab may also be added. Some examples of chemo regimens used for this lymphoma include:

Because this lymphoma tends to invade the area around the brain and spinal cord, the chemo drug methotrexate is often given into the spinal fluid (called intrathecal therapy). This may not be needed if high-dose methotrexate is given as a part of the main chemotherapy regimen.

An important part of the initial treatment of this disease is making sure a person gets plenty of fluids, as well as drugs like allopurinol, to help prevent tumor lysis syndrome (described in Chemotherapy for Non-Hodgkin Lymphoma).

If the lymphoma doesn’t go away or if it comes back after treatment, another chemo regimen might be tried. If the lymphoma goes into remission, the doctor might suggest a stem cell transplant.

The main treatment for this lymphoma is usually chemo or rituximab. For more detailed information see Treating Waldenstrom Macroglobulinemia.

This is a slow-growing lymphoma that tends to invade the spleen and lymph nodes as well as the blood. Patients without symptoms often don’t need to be treated right away. When treatment is needed, most often the chemo drugs cladribine (2-CdA) or pentostatin are used. For more detailed information, see Treating Chronic Lymphocytic Leukemia.

This lymphoma begins in the brain or spinal cord. It often develops in older people or those with immune system problems caused by AIDS or drugs given to keep transplanted organs from being rejected.

Most patients are treated with chemo and/or radiation. One problem with treating this disease is that most chemo drugs commonly used to treat lymphoma don’t reach the brain when given intravenously (IV). For people in reasonably good health, high IV doses of the drug methotrexate have been shown to be the most effective treatment. This is given along with the drug leucovorin and IV fluids, which help limit serious side effects. Other chemo drugs, such as cytarabine, may be added. Rituximab may be added as well. For those who aren’t able to tolerate this treatment, other, less intensive chemo regimens or radiation therapy alone may be tried.

An issue with radiation therapy to the brain, especially in older patients, is that it can often cause mental changes. Doctors limit the dose of radiation to try to lessen this problem.

If CNS lymphoma keeps growing or comes back after treatment, further options may include chemo (using different drugs), radiation therapy, or a stem cell transplant if the person is healthy enough.

Most often doctors treat these cancers with radiation therapy, chemotherapy (chemo), or a combination of the two.

External beam radiation therapy is given if the cancer is limited to the eye. Radiation to both eyes may be recommended if lymphoma is found in both eyes. Because these lymphomas are commonly linked with lymphoma of the brain (CNS lymphoma), they have sometimes already spread outside the eye or to the brain when the cancer is first diagnosed. If this is the case, radiation therapy to the brain and spinal cord may be included because it can help prevent the lymphoma from spreading there or help destroy cancer cells that are there but haven’t been seen by imaging. Problems with thinking, concentration, and memory are possible side effects from radiation to the brain and spinal cord.

Depending on the type of lymphoma, chemo may be used alone or in combination with radiation therapy, especially if it has grown outside the eye or spread to other places in the body. Chemo can be given into a vein (systemic chemo), directly into the cerebrospinal fluid (intrathecal chemo), or directly into the eye (intraocular chemo). Intraocular chemo gets higher doses of the drug to the tumor without causing severe side effects in other parts of the body. Methotrexate is the most commonly used chemo drug, but others can be used as well. Monoclonal antibodies such as rituximab may also be given directly into the eye. The best combination and dosage of drugs is not yet known, and the choice may be influenced by the type of lymphoma. Sometimes systemic chemo may be given along with therapy given directly to the eye such as external radiation or intraocular chemo.

If the lymphoma does not respond to treatment or if it comes back (recurs), high-dose chemotherapy followed by a stem cell transplant may be an option for some people.

The treatment information given here is not official policy of the American Cancer Society and is not intended as medical advice to replace the expertise and judgment of your cancer care team. It is intended to help you and your family make informed decisions, together with your doctor. Your doctor may have reasons for suggesting a treatment plan different from these general treatment options. Don’t hesitate to ask him or her questions about your treatment options.

The type of cancers that affect the lymphatic system, known as lymphoma, can be either Hodgkin’s lymphoma or non-Hodgkin’s lymphoma, depending on the disease characteristics.

Most non-Hodgkin’s lymphomas originate in the B-cells, which make them B-cell non-Hodgkin’s lymphomas, rather than T-cell lymphomas. The reasons for the development of one or the other is not completely understood, but their origin influences both prognosis and treatment.

Importance of B-cells in lymphoma

Non-Hodgkin’s lymphoma develops as a result of an abnormal amount of a type of white blood cell called lymphocytes. The lymphocytes do not die and give space to new ones, as they would in healthy people. Instead, they continue growing and multiplying inside the lymph nodes, leading to swelling. B-cells are responsible for combating the infections through the production of antibodies.

The different types of B-cell non-Hodgkin’s lymphomas include diffuse large B-cell lymphoma (DLBCL), the most common non-Hodgkin’s lymphoma in the U.S., estimated by the American Cancer Society to be about one in every three cases; primary mediastinal (thymic) large B-cell lymphoma, a subtype of DLBCL; follicular lymphoma, estimated in one out of five lymphomas in the U.S. by the ACS; chronic lymphocytic leukemia/small lymphocytic lymphoma; extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone lymphoma; mantle cell lymphoma; and Burkitt lymphoma.

B-Cell lymphoma diagnosis

One of the most common symptoms associated with lymphoma is the presence of swollen lymph nodes, also known as lymphadenopathy. The enlarged nodes do not cause pain but may be uncomfortable and felt beneath the skin, particularly in the neck and armpits. Other symptoms include night sweats or fevers, unexplained weight loss, or a lack of appetite. In more severe cases, patients experience difficulty breathing, pain and distention, and fatigue.

Since these symptoms can indicate lymphoma or a series of other conditions, physicians often conduct numerous tests to confirm the diagnosis. A biopsy and bone marrow examination are the most common diagnostic procedures, but flow cytometry and immunohistochemical stains of the biopsied material can also be conducted, as well as thoracentesis in patients with pleural effusion and paracentesis, in cases of ascites.

Treatment of B-cell lymphoma

The origin of the lymphoma is crucial to determine a proper treatment. The most common treatments to address B-cell lymphoma are radiation therapy, particularly in early stages and to respond to eventual complications; curative and palliative chemotherapy; and biologic therapy. However, the treatment is usually personalized to both the stage of the disease and the type of lymphoma.

Follicular lymphoma is usually treated with alkylating agents and rituximab, while splenic marginal zone lymphoma is often addressed with a splenectomy. Extranodal B-cell lymphoma of MALT may be treated with antibiotics, surgery, or systemic chemotherapy, and mantle cell lymphoma is usually treated with combined chemotherapy.

Diffuse large B-cell lymphoma is treated with rituximab and cyclophosphamide, hydroxydaunorubicin, vincristine (Oncovin), prednisone, and bleomycin (R-CHOP), while mediastinal diffuse large B-cell lymphoma is generally treated with radiation therapy. Burkitt lymphoma may be addressed with combined chemotherapy sessions with central nervous system prophylaxis.

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Note: Lymphoma News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

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