Lymphocytic Lymphoma

Lymphocytic lymphoma, also known as small lymphocytic lymphoma (SLL), is closely related to chronic lymphocytic leukemia (CLL). These are essentially the same disease, differing only in where cancer cells are most concentrated—in the lymph nodes for SLL, or in the blood and bone marrow for CLL.

Table of contents

• What is Small Lymphocytic Lymphoma and Chronic Lymphocytic Leukemia?
• Signs and Symptoms
• Causes and Risk Factors
• Diagnosis and Testing
• Treatment Options
• Living with the Disease

What is Small Lymphocytic Lymphoma and Chronic Lymphocytic Leukemia?

Small lymphocytic lymphoma, SLL, Chronic lymphocytic leukemia, CLL

Small lymphocytic lymphoma (SLL) and chronic lymphocytic leukemia (CLL) are cancers that affect lymphocytes, which are a type of white blood cell that helps the body fight infections^[1]. These conditions are essentially the same disease, with the only difference being where the cancer cells are primarily located in the body^[1].

When most of the cancer cells are found in the bloodstream and bone marrow, the disease is called CLL. When the cancer cells are located mostly in the lymph nodes, it is called SLL^[1]. Both conditions are types of non-Hodgkin lymphoma, which is a category of cancers affecting the lymphatic system^[2].

• Blood
• Bone marrow
• Lymph nodes
• Spleen
• Liver

In these conditions, abnormal B cells (a specific type of lymphocyte) grow and spread. These cancer cells can crowd out healthy cells in several parts of the body^[4]. The disease typically grows slowly over time^[2]. CLL/SLL can affect the lymph nodes, spleen, blood, bone marrow, and other parts of the body^[2].

CLL is one of the most common types of leukemia in adults, accounting for about one-third of all new leukemia cases in the United States^[4]. The estimated number of new CLL cases for 2025 is 23,690^[4]. The condition is more common among men, and the median age at diagnosis is 69 years old^[4].

Signs and Symptoms

Many patients with CLL/SLL do not have any obvious symptoms when first diagnosed. Doctors might detect the disease during routine blood tests or a physical examination^[1]. For many patients, a diagnosis can come as a shock because they may not feel sick and may not experience symptoms for years^[4].

When symptoms do occur, they may include swollen lymph nodes that are tender but painless, commonly found in the neck, underarms, stomach, or groin^[1][8]. Many people experience fatigue or feeling tired, which is one of the most common symptoms^[1][4].

Additional symptoms can include shortness of breath, anemia (low red blood cell count), bruising easily, night sweats, unexpected weight loss, and frequent infections^[1][8]. Some patients may experience pain or a feeling of fullness below the ribs on the left side, which can be caused by an enlarged spleen^[4]. Others may have a tender, swollen abdomen and feel full even after eating only a small amount^[1].

As the disease progresses, patients may also experience fever, chills, and petechiae, which are flat, pinpoint, dark-red spots under the skin caused by bleeding^[8]. However, many patients with CLL/SLL will live for years without developing symptoms^[1].

Causes and Risk Factors

Scientists know that CLL is caused by changes, called mutations, in genes that control the growth of bone marrow cells. However, the exact reason for those changes is unknown^[6].

White people over age 50 are more likely to develop CLL^[6]. The condition is more common among men than women, particularly white men^[4].

Several risk factors have been identified for developing CLL. Having a family history of CLL or other bone and blood marrow cancers increases risk^[6]. Exposure to Agent Orange, an herbicide used in the Vietnam War, is also considered a risk factor^[6]. Additionally, people with monoclonal B-cell lymphocytosis (MBL), a precancerous condition that causes an increase in B cells, have a higher risk of developing CLL^[6].

Diagnosis and Testing

Diagnosis of CLL/SLL often begins with a physical exam, which checks for swollen lymph nodes in the neck, underarms, and groin, as well as an enlarged spleen^[9]. A routine blood test can detect changes in blood cell counts, which is often the first step leading to a CLL diagnosis^[4].

Several blood tests are used to diagnose CLL. A complete blood count measures the number of cells in a blood sample. A high number of B cells could indicate CLL^[9]. In CLL, lymphocyte counts in the blood are usually greater than or equal to 5,000/mm³^[12].

A peripheral blood smear examines the size, shape, and appearance of cells in the blood. In CLL, this test may show many small, round lymphocytes, sometimes called smudge cells^[9]. Flow cytometry is used to identify specific proteins on the surface of cancer cells, helping to confirm the diagnosis. CLL cells typically show a characteristic pattern of being CD5- and CD23-positive B cells^[12].

Fluorescence in situ hybridization (FISH) testing looks for changes in cancer cell DNA, which can provide important information about how the condition may progress over time and help inform treatment decisions^[4][9]. This includes testing for deletions in chromosomes, such as del(11q), del(13q), del(17p), and trisomy 12^[12].

Additional tests may include checking serum immunoglobulin levels, testing for hepatitis B and C and HIV, and measuring lactate dehydrogenase and beta-2-microglobulin levels^[12]. Bone marrow biopsy and aspiration are procedures that collect cells from the bone marrow for testing, though these are usually not required for diagnosis^[6][9].

Imaging tests such as computed tomography (CT) are usually not required in the absence of peripheral swelling. However, if there is extensive swelling on examination, investigating retroperitoneal adenopathy may be helpful^[12].

Treatment Options

Not everyone with CLL/SLL needs treatment right away. Many patients are initially managed with an approach called active surveillance, also known as “watch and wait” or “watchful waiting”^[10][13]. With this strategy, patients’ overall health and disease are monitored through regular checkup visits and various tests, such as laboratory and imaging tests^[13].

Research has shown that treating CLL before there are certain signs of disease progression does not help people live longer. Because of this, and because treatments can cause side effects, many people who are diagnosed with CLL start with active surveillance^[10]. Studies have shown that patients with less advanced disease managed with active surveillance have outcomes similar to those who are treated early in the course of the disease^[13].

Active treatment is started when patients begin to develop lymphoma-related symptoms or there are signs that the disease is progressing based on testing during follow-up visits^[10][13]. When treatment does begin, it depends on the stage of the disease, the patient’s symptoms, age and overall health, and the benefits versus side effects of treatment^[13].

The main treatments for CLL/SLL are targeted therapy and chemoimmunotherapy, which combines chemotherapy with immunotherapy^[10][14]. Targeted therapy uses drugs to target specific molecules on cancer cells and aims to stop the cancer from growing or help the immune system fight the cancer^[14]. Chemotherapy uses medicines to kill cancer cells, and it is usually given with targeted cancer medicines at the same time^[14].

Common drugs or drug combinations used as initial treatments for CLL/SLL include acalabrutinib (Calquence), ibrutinib (Imbruvica), venetoclax (Venclexta), zanubrutinib (Brukinsa), and various combinations with rituximab (Rituxan), obinutuzumab (Gazyva), bendamustine (Treanda), fludarabine (Fludara), cyclophosphamide (Cytoxan), chlorambucil (Leukeran), ofatumumab (Arzerra), and pentostatin^[13].

Treatment choice may vary depending on whether the patient’s lymphoma cells are missing parts of certain chromosomes, particularly a deletion in the smaller arm of chromosome 17 (called a 17p deletion)^[13].

Additional treatment options may include radiation therapy, which uses high-energy rays of radiation to kill cancer cells^[14]. Rarely, surgery may be needed to remove the spleen if symptoms get worse or other treatments are not working well^[14]. Other treatment options being studied include bone marrow transplant (also known as stem cell transplant), CAR T-cell therapy, and clinical trials^[2][10].

Supportive treatments may also be needed to prevent or control symptoms caused by CLL/SLL. These can include medicines to prevent infections, vaccines to prevent illnesses such as the flu, pneumonia, and COVID-19, blood or platelet transfusions, and steroid medicines^[14].

It’s important to understand that treatments usually cannot cure small lymphocytic lymphoma, but they may control it for a long time^[2]. Patients with this type of cancer often have a good prognosis^[2]. Many patients will live for years with the disease and may need to repeat treatment several times^[14].

When symptoms come back after treatment, this is called a relapse. This may happen slowly and patients may not need treatment right away. Patients may have several relapses while living with CLL. When symptoms are under control, this is called remission, which can last for years^[14].

Living with the Disease

Living with CLL/SLL requires ongoing care and attention to both physical and emotional health. Taking time for yourself to relax and de-stress is a valuable part of recovery^[15].

Staying physically active is considered an important component of cancer care. Research has shown that exercise and physical activity can improve fatigue, quality of life, and immune system function^[19]. A brisk walk or bike ride can provide moderate aerobic exercise. The American Cancer Society recommends 150 to 300 minutes of moderate exercise each week, but patients can slowly work their way up to 30 minutes or more each day^[19].

Eating a well-balanced diet can support overall health. A nutritious diet and healthy weight can improve strength during cancer treatment and help better tolerate side effects^[19]. The best diet for CLL includes plenty of fruits and vegetables, low-fat protein and dairy, whole grains, and olive oil or other healthy oils. Patients should avoid foods with trans fats or added sugar and try not to eat more than 2,300 milligrams of sodium per day^[19]. Drinking plenty of water to stay hydrated and avoiding smoking are also important^[19].

Because CLL affects the immune system and makes it harder to fight infections, taking basic precautions to avoid getting sick is important^[19]. Patients should follow food safety guidelines and may need to avoid certain activities that increase infection risk.

Coping with the emotional impact of having lymphoma is unique to each patient’s personality and situation^[17]. Maintaining a strong support system is important. This can include communicating fears and concerns with family, friends, doctors, and counselors, or writing down concerns in a journal^[17]. Finding a support group or other individuals who are also coping with cancer can be helpful^[17].

Feeling sad or depressed is not unusual for people living with cancer. Signs of depression can include sleeping more or less than usual, feeling a lack of energy, crying, or inability to concentrate. Patients experiencing these symptoms should ask for a referral to a psychiatrist, social worker, psychologist, or counselor who can help through talk therapy, medications, or both^[17].

Patients will have regular check-ups during and after any treatments, which may include tests and scans^[14]. Regularly tracking test results and symptoms gives patients and their doctors a picture of how they are doing over time, allowing them to spot patterns and address anything that needs attention^[4]. It’s important to tell the doctor how you are feeling and if you are experiencing any new symptoms. Taking an active role in care is essential^[4].