Small lymphocytic lymphoma (SLL) is a subtype of non-Hodgkin lymphoma (NHL), a blood cancer related to leukemia, myeloma, and myeloproliferative neoplasms MPNs. Like its leukemia counterpart chronic lymphocytic leukemia (CLL), SLL tends to occur in older adults.

What Is Small Lymphocytic Lymphoma?

SLL is an indolent (slow-growing) form of B-cell lymphoma. Lymphomas are cancers of the lymphatic system, which includes the lymph nodes, spleen, and other organs that remove bacteria, waste, and excess fluid from the body. In SLL, cancer cells form in the lymphatic system from B lymphocytes (B cells), a type of white blood cell that produces antibodies and helps fight infections.

SLL vs. CLL

SLL and B-cell CLL are considered different forms of the same disease. However, because they are treated the same way, they are often discussed together as CLL/SLL.

The important difference between the two diseases is that SLL forms solid tumors in the lymph nodes whereas CLL cancer cells are found mostly in the blood and bone marrow. Moreover, CLL is the most common type of adult leukemia, while SLL represents about 6 percent of all non-Hodgkin lymphomas. CLL also has several different subtypes. The condition involves B cells in about 95 percent of cases, but other subtypes of CLL can affect T cells (another type of white blood cell).

Signs and Symptoms of SLL

Given that SLL is a slow-growing lymphoma, it often does not cause symptoms until it has become more advanced. Rather, SLL is usually diagnosed after routine exams or blood tests come back with abnormal results.

There are many symptoms that can be seen in all types of NHL, but no symptoms that are unique to SLL. Symptoms may include:

• Swollen or enlarged lymph nodes, felt as painless lumps in the neck, groin, or armpits
• Fever that cannot be explained by an infection or other causes
• Night sweats, or excessive sweating while sleeping that sometimes soaks your sheets or clothes
• Unexplained weight loss that occurs without a change in diet, exercise, or medication
• Fatigue, or persistent physical or mental tiredness or exhaustion that does not improve with rest

Other symptoms may depend on where in the body the cancer is.

• Swollen lymph nodes or an enlarged spleen due to lymphoma may cause local symptoms.
• Lymphoma in the chest may cause chronic cough, pain or pressure in the chest, shortness of breath, and difficulty breathing.
• In the abdomen, SLL may have symptoms such as swollen belly, loss of appetite, nausea and vomiting, and abdominal pain.
• SLL in the bone marrow may cause frequent Infections.
• SLL in the brain may cause headaches, changes in personality, difficulty thinking, and seizures.

Read more about symptoms of lymphoma.

Diagnosis of Small Lymphocytic Lymphoma

To diagnose SLL, your doctor will likely begin by taking a thorough medical history. They will also conduct a physical exam to identify your risk factors and any symptoms and physical signs of disease you have. The doctor may also want to take biopsies of lymph nodes and bone marrow and to conduct imaging tests and blood tests.

Biopsy

Biopsies entail taking a sample of tissue from a tumor, bone marrow, or bodily fluid, used for identifying cancer cells. Depending on the size and location of suspected cancer cells, a biopsy may involve surgery to remove all or part of a tumor, or it may involve taking a sample of a tumor or fluid using a needle. If a doctor suspects you have a condition related to bone marrow, they may perform a biopsy to remove a small portion of bone and bone marrow.

Imaging

Imaging tests can help find tumors throughout the body and may include:

• X-rays
• CT scans
• Positron emission tomography scans
• MRI scans

Finding out where cancer cells are located in the body also helps doctors determine the stage of a person’s cancer.

Blood Tests

A complete blood count (CBC) is the most important blood test for diagnosing SLL (as well as other non-Hodgkin lymphomas and leukemias).

CBC testing measures the amount of red blood cells, hemoglobin, white blood cells, and platelets in a blood sample. Further analysis, called differential analysis, looks at the different types of white blood cells present in a blood sample and whether or not they appear abnormal.

Other blood tests that can help identify cancer include lactate dehydrogenase and beta-2 microglobulin tests. Standard tests for liver and kidney function, as well as tests for conditions such as HIV and hepatitis B and C, are also often needed to help decide what treatments are the most appropriate.

Additional Tests

Cells taken from a tumor, bone marrow, and the blood may be further studied in a lab to look for genes and proteins that can help identify specific types of cancer. This testing can help doctors estimate the prognosis (outlook) and figure out what treatments will likely work best.

These lab tests may include:

• Immunophenotyping tests, such as flow cytometry, in which a machine uses antibodies to “read” the proteins found on the surface of cancer cells
• Cytogenetic tests, such as fluorescence in situ hybridization or gene-mutation tests, to identify specific cancer genes in SLL cells
• Serum immunoglobulin tests to show whether white blood cells are working correctly or if they are abnormal

Learn more about diagnosing lymphoma.

Stages of Small Lymphocytic Lymphoma

Cancer staging is another tool used to predict a person’s outlook and determine which treatments may be most helpful.

Lymphomas are staged using the Lugano classification system. Stages are based on whether the lymphoma is localized or widespread, especially if the lymphoma has spread from one side of the diaphragm to the other. Stages are defined further by the size (bulk) of the tumor and whether or not lymphoma has spread beyond the lymphatic system. There are four stages. In stages 1 and 2, the cancer is limited to one side of the diaphragm and involves lymph nodes or one organ outside the lymphatic system. In stages 3 and 4, advanced lymphoma has spread to both sides of the diaphragm and may include organs outside of the lymphatic system.

SLL may also be staged the same way as CLL if there are many cancer cells present in the blood and bone marrow. CLL stages are described differently than other cancer stages and include criteria based on the amount of different types of blood cells as well as tumor location. In the United States, CLL staging uses the Rai system (0 to 4) and in Europe, the Binet system is used (A, B, or C).

Read more about the stages of small lymphocytic lymphoma.

Treatment of Small Lymphocytic Lymphoma

Because CLL/SLL is a very slow-growing cancer, it does not always require immediate treatment. Your doctor will usually consider a variety of factors (including your age, overall health, personal preferences, stage, and specific genes and proteins found in the cancer cells) to determine the best treatment plan, which may include waiting, using medication, or other approaches.

Watch and Wait

People diagnosed with CLL/SLL who do not have any symptoms may not require any treatment until symptoms develop. This watch-and-wait approach, also called active surveillance, requires regular follow-up visits with a doctor to monitor the progress of the disease. If symptoms begin to develop or lab tests show that CLL/SLL is getting worse, then your doctor may recommend that you begin treatment.

Medications

Treatment for CLL/SLL usually includes multiple drugs, such as targeted therapy medications and chemotherapy drugs. Chemotherapy drugs kill cancer cells by preventing them from growing and dividing. Targeted therapies, such as monoclonal antibodies and small-molecule drugs, attack cancer cells more precisely by targeting proteins and genes specific to cancer cells, causing fewer side effects than chemotherapy. Initial treatment may only involve targeted therapy drugs without chemotherapy.

Targeted therapy drugs, which may be used alone or in combinations, include:

• Arzerra (ofatumumab)
• Calquence (acalabrutinib)
• Gazyva (obinutuzumab)
• Imbruvica (ibrutinib)
• Rituxan (rituximab)
• Treanda (bendamustine)
• Venclexta (venetoclax)

One important combination treatment is called FCR and includes the chemotherapy drugs Fludara (fludarabine) and Cytoxan (cyclophosphamide) and the aforementioned Rituxan.

For relapsed CLL/SLL, treatment may include Zydelig (idelalisib) or Copiktra (duvelisib).

Stem Cell Transplant

Certain people with CLL/SLL — those who are younger, without other major health issues, and who are at risk for relapse — may be candidates for allogeneic stem cell transplantation. This aggressive treatment uses high-dose chemotherapy to kill both cancer cells and stem cells (which make new blood cells) in the bone marrow. After chemotherapy, new stem cells are transplanted from a donor to regrow healthy bone marrow and blood cells.

Other Treatments

Other procedures are sometimes used to treat specific CLL/SLL symptoms. For example, enlarged lymph nodes may be treated with radiation therapy. An extremely enlarged spleen may require surgery to remove it. Additionally, people with CLL/SLL may be able to access new treatment options by participating in clinical trials.

Outlook for CLL/SLL

Generally, 86.9 percent of people with CLL/SLL will live for at least five years after being diagnosed. However, your doctor can make a better estimate of your individual prognosis by assessing several factors. Some factors that may lead to a worse prognosis include:

• Older age
• Involvement of organs outside the lymphatic system
• Advanced Lugano stage (stage 3 or 4)
• High levels of lactate dehydrogenase or beta-2 microglobulin
• Specific gene changes within cancer cells
• High levels of specific proteins in cancer cells
• Fast-growing lymphocytes
• High numbers of prolymphocytes (a type of immature white blood cell)

Your doctor may also use a system called the CLL International Prognostic Index (CLL-IPI) to help estimate your outlook. The CLL-IPI takes into account specific gene mutations, cancer stage, and your age to generate a risk score that provides information about prognosis and treatment. A lower risk score means that you are more likely to have a better outcome and you may not require treatment. However, a higher risk score may have a worse prognosis and your doctor may recommend more aggressive treatment.

Read more about lymphoma and leukemia treatments.

Talk With Others Who Understand

MyLymphomaTeam is the social network for people with lymphoma and their loved ones. On MyLymphomaTeam, more than 8,000 members come together to ask questions, give advice, and share their stories with others who understand life with lymphoma.

Are you or someone you care for living with CLL/SLL? Share your experience in the comments below, or start a conversation by posting on MyLymphomaTeam.