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 develop 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 include 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.

Which Is More Serious, CLL or SLL?

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

The difference between the two diseases is that SLL forms solid tumors in the lymph nodes, whereas CLL cancer cells are 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. The difference is based on how many abnormal B-lymphoid cells are found in the blood. In SLL, the absolute lymphocyte count is less than 5,000 per microliters, whereas in CLL, it’s 5,000 or more.

CLL also has different subtypes. In about 95 percent of cases, it involves B cells, a type of white blood cell. However, some subtypes of CLL affect white blood cells called T cells.

Small Lymphocytic Lymphoma Symptoms

Because SLL is a slow-growing lymphoma, it often doesn’t cause symptoms until it’s more advanced. SLL is usually diagnosed after routine exams or blood tests with abnormal results.

Many symptoms show up in all types of NHL but none that are specific to SLL. Symptoms may include:

• Swollen or enlarged lymph nodes, felt as painless lumps in the neck, groin, or armpits
• Fever with no clear cause, such as an infection or other known reason
• Night sweats, or excessive sweating while sleeping that sometimes soaks your sheets or clothes
• Unexplained weight loss without a change in diet, exercise, or medication
• Fatigue, which is persistent physical or mental tiredness or exhaustion that doesn’t improve with rest

Other symptoms may depend on where the cancer is:

• Swollen lymph nodes or an enlarged spleen due to lymphoma may cause local symptoms, which are symptoms in one area of the body.
• Lymphoma in the chest may cause an ongoing cough, pain or pressure in the chest, shortness of breath, and difficulty breathing.
• In the abdomen, SLL may cause symptoms such as a 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, blurred vision, changes in personality, difficulty thinking, and seizures.

Diagnosis of Small Lymphocytic Lymphoma

To diagnose SLL, your doctor will likely start by asking about your medical history. They’ll also do a physical exam to look for any risk factors, symptoms, or signs of disease. The doctor may also recommend taking biopsies (samples) of your lymph nodes or bone marrow, along with imaging tests and blood tests.

Biopsy

Doctors take biopsies to make a final diagnosis of SLL or CLL. This procedure involves taking a small tissue or fluid sample to look for cancer cells. Your doctor may use a needle to remove the sample. Sometimes, surgery may be needed. If a doctor thinks you have a condition related to bone marrow, they may perform a biopsy to remove a small sample of bone and bone marrow.

Imaging

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

• CT scans
• Positron emission tomography (PET) scans
• Ultrasound scans

Finding out where cancer cells are in the body also helps doctors figure out the stage of the 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).

Flow cytometry is the gold standard for diagnosing CLL. This test looks for markers on the outside of cells to determine whether they’re cancerous. Doctors use flow cytometry to find CLL cells in blood and bone marrow samples.

CBC testing measures the amount of red blood cells (RBCs), hemoglobin, white blood cells, and platelets in a blood sample. Further testing, called a differential analysis, looks at the different types of white blood cells in a blood sample and shows if any are abnormal.

Other blood tests that can help find cancer and give clues about how serious it is include lactate dehydrogenase and beta-2 microglobulin tests. Doctors also usually check how well your liver and kidneys are working, and test for infections like HIV and hepatitis B and C. These results can help guide the best treatment plan for you.

Additional Tests

Cells from a tumor, bone marrow, or blood can be studied in a lab to look for certain genes and proteins. These tests help doctors figure out the exact type of cancer, what your prognosis (outlook) might be, and which treatments are likely to work best.

These lab tests may include:

• Cytogenetic tests, including a special test called fluorescence in situ hybridization (FISH), to look for cancer-related genes in SLL/CLL cells
• Serum immunoglobulin tests to check if your white blood cells are working normally or if something is wrong

Stages of Small Lymphocytic Lymphoma/CLL

Cancer staging is another tool used to predict a person’s prognosis and determine which treatments may be most helpful. Traditionally, NHL is staged using the Lugano classification system. This system uses four stages that describe how far the cancer has spread and which organs are affected.

On the other hand, doctors classify SLL and CLL using different systems. The Rai system is more common in the United States, while the Binet system is used in Europe. SLL doesn’t usually form tumors — instead, staging depends on lymphocyte counts and affected organs. Lymphocytosis refers to a high lymphocyte number in the blood and bone marrow without an infection.

There are five stages in the Rai system:

• Stage 0 — Lymphocytosis but no other organs affected, normal RBC and platelet counts
• Stage 1 — Lymphocytosis with enlarged lymph nodes, normal RBC and platelet counts
• Stage 2 — Lymphocytosis with enlarged spleen, lymph nodes may or not be enlarged, normal RBC and platelet counts
• Stage 3 — Lymphocytosis, spleen, lymph nodes, and liver may or may not be enlarged, low RBC counts, platelet counts normal
• Stage 4 — Lymphocytosis, enlargement of the spleen, lymph nodes, and/or liver, low RBC and platelet counts

Read more about how SLL/CLL is staged.

Small Lymphocytic Lymphoma Treatment

Because CLL/SLL is a very slow-growing cancer, it doesn’t always require immediate treatment. Your doctor will consider 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 early-stage CLL/SLL who don’t have any symptoms usually don’t start treatment right away. Instead, doctors use a “watch-and-wait” approach called active surveillance.

You’ll have blood tests every three months for one year to monitor how your SLL/CLL is doing. If symptoms begin to develop or lab tests show that CLL/SLL is getting worse, then your doctor may recommend starting treatment. You’ll need to have signs of active disease, which can include:

• Massive enlargement of the lymph nodes and spleen
• New or worsening NHL symptoms like fatigue, fever, and night sweats
• Signs of bone marrow failure, as seen with blood tests

Active surveillance is the best approach in early-stage CLL/SLL without symptoms. Studies show that treating people too early doesn’t provide any benefits. In fact, you’re more likely to experience more unwanted side effects from the cancer drugs. This is true for targeted therapies, which will be discussed later.

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 attack cancer cells more precisely. They target proteins and genes specific to cancer cells, causing fewer side effects than chemotherapy. Most doctors treat SLL/CLL with targeted therapies first.

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

• Acalabrutinib (Calquence)
• Bendamustine (Treanda)
• Ibrutinib (Imbruvica)
• Obinutuzumab (Gazyva)
• Ofatumumab (Azerra)
• Rituximab (Rituxan)
• Venetoclax (Venclexta)

One important combination treatment is called FCR. It includes the chemotherapy drugs fludarabine, cyclophosphamide, and rituximab.

For relapsed CLL/SLL, treatment may include idelalisib (Zydelig) or duvelisib (Copiktra). Your doctor may also prescribe other first-line medications — treatments that are usually tried first — that you haven’t used before. Examples include venetoclax in combination with other targeted therapies.

Bone Marrow 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 bone marrow transplantation with cells from a donor. 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, which are studies that test if new treatments are safe and work well.

Read more about oral treatments vs. chemotherapy for indolent forms of NHL.

Outlook for Small Lymphocytic Leukemia

Generally, 88.1 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 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 the CLL International Prognostic Index (CLL-IPI) to help estimate your prognosis. The CLL-IPI takes into account specific gene mutations (changes), your cancer stage and age to generate a risk score that provides information about prognosis and treatment. Certain factors have higher scores that point to a lower prognosis. Examples of these markers include:

• Higher levels of beta-2 microglobulin in your bloodstream
• Absence of mutations in the IGHV gene
• SLL cells that have the ZAP70 marker (a protein that can mean the disease may grow faster)

A lower risk score means you’re more likely to have a better outcome and may not need treatment. However, a higher risk score may have a worse prognosis and your doctor may recommend more aggressive treatment.

Complications of Small Lymphocytic Leukemia

People with SLL/CLL are at risk of developing certain complications. Because this cancer affects the immune system, you’re more likely to develop autoimmune complications, where the body’s immune system mistakenly attacks its healthy cells. Examples of these complications include:

• Low antibody levels, which raise your risk of bacterial infections
• Thrombocytopenia (low platelet levels)
• Hemolytic anemia with low RBC counts because your bone marrow can’t replace dying RBCs fast enough
• More severe symptoms from insect stings, like mosquito bites

Ask Your Doctor

SLL is a slow-growing type of cancer that often doesn’t cause symptoms at first. Many people can live with SLL for years, and treatment isn’t always needed right away. But when it is, there are several options, including targeted therapies, chemotherapy, and sometimes a bone marrow transplant. Your doctor will help decide what’s best based on your health, test results, and cancer stage. Regular checkups are important to watch for changes and catch any problems early.

Talk With Others Who Understand

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