Small Lymphocytic Lymphoma: Overview and More

This slow-growing cancer isn't curable but can be properly managed for years

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Small lymphocytic lymphoma (SLL) is a type of cancer that affects small organs called lymph nodes. Specifically, it affects white blood cells known as B-cell lymphocytes that help the body fight infection. When you have SLL, your body will start to produce immature, cancerous B-cells in the lymph nodes.

In the early stages, you may not experience any symptoms, but, over time, the disease can cause the generalized swelling of the lymph nodes accompanied by fever, night sweats, and weight loss. SLL can be diagnosed with a combination of blood tests, imaging studies, and a biopsy of affected tissues.

SLL is an indolent (slow-growing) cancer. If you have no symptoms, your healthcare provider may take a watch-and-wait approach and delay treatment. If treatment is indicated, chemotherapy, radiation therapy, stem cell transplantation, and other approaches may be recommended.

Small lymphocytic lymphoma isn't curable, but people with the disease can live well for many years if it is properly managed, and do so with better long-term outcomes than other types of blood cancers.

Doctor checks for lymphadenopathy in senior man with small lymphocytic lymphoma
FatCamera / E+ / Getty Images


SLL belongs to one of two groups of the lymphomas known as non-Hodgkin lymphoma and is closely linked to another type of blood cancer, known as chronic lymphocytic leukemia (CLL), which also affects B-cells.

The key difference between SLL and CLL is their location.

  • With SLL, the accumulation of cancer cells occurs mainly in the lymph nodes but also can also affect the bone marrow.
  • With CLL (the more common of the two diseases), cancer cells are mainly found in the bloodstream as well as bone marrow.

SLL and CLL were once thought to be different diseases, but are today regarded as different manifestations of the same disease, referred to collectively as CLL/SLL.

Blood tests can help differentiate the diseases, but the treatment approach for each is more or less the same.

What Are the Symptoms of SLL?

There are often no symptoms in the early stages of SLL. In fact, SLL can remain asymptomatic (without symptoms) for years.

Small lymphocytic lymphoma symptoms, when they do appear, include:

  • Lymphadenopathy (swollen lymph nodes), typically painless and most commonly felt in the neck, armpits, and groin
  • Easy bruising
  • A swollen, tender abdomen (due to an enlarged spleen, or occasionally an enlarged liver)
  • A persistent feeling of fullness

In addition, there may be so-called "B symptoms" that are commonly experienced with most types of cancer. These include:

Between 5% and 10% of people with small lymphocytic lymphoma experience "B symptoms."


As cancer cells start to accumulate in bone marrow, they can disrupt the production of blood cells, leading to fatigue associated with anemia (low red blood cells) and the easy bruising associated with thrombocytopenia (low platelets).

The depletion of functional bone marrow can also trigger a severe form of anemia called autoimmune hemolytic anemia (AIHA) in which the immune system attacks healthy red blood cells (also known as erythrocytes).

AIHA affects between 10% and 15% of people with CLL/SLL. Symptoms include fatigue, pale skin, tachycardia (fast heartbeat), trouble breathing, chills, backache, and jaundice (yellowing of the skin or eyes). Cases that develop abruptly can be life-threatening.

A similar autoimmune disorder known as immune thrombocytopenic purpura can cause the immune system to attack healthy platelets (also known as thrombocytes), typically in people with advanced SLL.

Symptoms include excessive bruising, nosebleeds, bleeding gums, petechiae (superficial blood spots on the skin), hematuria (blood in urine), hematochezia (bloody stool), and heavy menstrual periods. Excessive bleeding in the urinary or gastrointestinal tract may require emergency treatment.

Because B-cells are responsible for the production of defensive antibodies, any depletion of these cells can increase the risk of recurrent infections. Advanced cases of SLL can also lead to bone marrow failure, in which bone marrow cannot keep up with the body's demand for healthy blood cells.

In rare cases, SLL can spontaneously transform into a more aggressive type of lymphoma called diffuse large B-cell lymphoma. The transformation, called Richter's syndrome, affects between 2% and 10% of people with CLL/SLL.

What Causes SLL and CLL?

Around 7% of all Non-Hodgkin lymphomas are classified as CLL/SLL, accounting for roughly 14,000 new diagnoses and 4,000 deaths in the United States each year.


The exact cause of SLL is unknown, but is largely believed to be the result of multiple genetic mutations, some of which may be inherited. The current body of research suggests that up to 80% of people with SLL have some form of chromosome abnormality, although the types can vary significantly.

Trisomies (in which three chromosomes are present instead of the normal two) are commonly seen in people with SLL. Studies suggest that as many as 30% of people with SLL have trisomy 12 (the second most common genetic aberration).

Even more commonly, the deletion of chromosome 13q14—in which there is a missing (deleted) copy of genetic material on chromosome 13—is seen in roughly 50% of cases. Both of these genetic anomalies are commonly passed from parent to child.

Studies have reported that up to 10% of people with SLL have a family member with the disease. When this occurs, offspring will often develop SLL 20 years earlier than the parent.

Other studies have suggested that having a parent or sibling with SLL increases your risk of the disease by six- to nine-fold. Even so, having a first-degree relative with the disease (or genetic anomaly associated with SLL) does not mean you will get SLL. Further research is needed.

Other Risk Factors

Beyond genetics and family history, there are a number of other risk factors associated with SLL. These include:

  • Age: Around 85% of cases occur after the age of 55, with the most (30.2%) diagnosed between 65 to 74.
  • Sex: Men are nearly twice as likely to get SLL than women (6% versus 3.4%, respectively).
  • Race/ethnicity: Whites are more frequently affected by SLL than other racial or ethnic groups. Around 10 of every 100,000 Whites are affected. By contrast, 7 of every 100,000 Blacks are affected, while 5 of every 100,000 Hispanics will get the disease. Asians are infrequently affected.

Other commonly cited risk factors include a prior hepatitis C infection and having an atopic disease such as eczema, a food allergy, hay fever, or asthma. How these conditions contribute to SLL remains unknown.

Blood transfusions, long thought to be a risk factor, have not been shown to contribute to the risk of SLL in any way. The same applies to prior radiation exposure.

How Is SLL Diagnosed?

SLL is typically diagnosed with a physical exam, blood tests, genetic tests, and a microscopic examination of biopsied tissues from the bone marrow or lymph nodes.

Physical Exam

As part of the investigation, the healthcare provider will conduct a review of your symptoms (including weight loss, night sweats, or fever) and medical history (including whether anyone in your family has a history of any type of blood cancer).

The physical exam may require you to undress. The healthcare provider will gently palpate (touch) the skin around your neck to check for enlarged cervical lymph nodes; under the arms for enlarged axillary lymph nodes; and around the groin for inguinal lymph nodes.

A key sign of lymphoma is the absence of pain in the affected lymph nodes. The nodes will also be mobile when touched rather than fixed.

The healthcare provider will also examine your abdomen to see if your spleen is enlarged, a condition referred to as splenomegaly. (The spleen is also a part of the lymphatic system along with the lymph nodes and is commonly affected by SLL.)

Liver enlargement (hepatomegaly) may also be revealed on physical examination in around 4% of cases, a finding that tends to suggest a poorer outcome.

Blood Tests

One challenge faced in the diagnosis of SLL is that the lymphadenopathy can often come and go in the early stages or affect one part of the body more than another. It is for this reason that blood tests are essential for the diagnosis of SLL.

Key to the investigation is a complete blood count, a panel of blood tests that looks at the quantity and comparative ratios of different cells in a sample of blood. The first diagnostic sign of SLL is an abnormally high lymphocyte count, referred to as lymphocytosis.

Small lymphocytic lymphoma vs. CLL

A complete blood count can also help differentiate SLL from CLL. With SLL, the lymphocyte count will be high, but will still under 5,000 cells per micrometer (µL). With CLL, the lymphocyte count will often be over 15,000 cells/µL, given that cancer cells are circulating in the bloodstream rather than being contained within the lymph nodes.

The challenge with diagnosing SLL is that many healthy people without the disease can have lymphocyte counts in the same range. Because of this, healthcare providers will also look at red blood cells and platelets for signs of anemia or thrombocytopenia, providing evidence of blood marrow suppression.

Leukocytes, another type of white blood cell produced in bone marrow, may also be low. These cellular dynamics (high lymphocytes accompanied by low erythrocytes/thrombocytes/leukocytes), paired with the development of lymphadenopathy and/or splenomegaly, are strong indications of SLL.

Imaging Studies

In addition to blood tests, your healthcare provider may order a computed tomography (CT) scan to look for lymphadenopathy in parts of the body than can't be palpated. CT scans take multiple coordinated X-ray images to create three-dimensional "slices" of internal structures.

The CT scan is performed with a contrast dye, either injected into a vein or taken by mouth, that can help better visualize swollen lymph nodes. This can also help differentiate SLL from CLL if swollen lymph nodes are found in the chest (mediastinal lymphadenopathy), abdomen (mesenteric lymphadenopathy), or other parts of the body.

Positron emission tomography (PET), an imaging study used to detect areas of disease activity, is not commonly used for the initial diagnosis of SLL but can help stage and manage the disease.


Immunophenotyping is a test that can help diagnose or classify blood cancers like lymphoma or leukemia. The test employs a technology called flow cytometry that can identify the physical characteristics of a cell as it is passed in front of a laser beam at rapid speed. Blood, bone marrow, and other cell samples can be tested.

The test can identify and categorize proteins on the surface of cells using a system called cluster of differentiation (CD). The CD classifications, totaling well over 370, can help pathologists identify SLL and differentiate between SLL and CLL.

Flow cytometry is typically combined with a staining process called fluorescence in situ hybridization (FISH) that can identify the genetic material of cancer cells.

SLL is identified by the presence of CD20 proteins on the surface of cancer cells alongside abnormal CD5 and CD23 proteins. Moreover, the cells will be clonal (genetically identical). These characteristics can provide healthcare providers with a definitive diagnosis of the disease.


If the immunophenotyping is unable to confirm SLL, your healthcare provider may recommend a lymph node biopsy. This involves the surgical removal of an enlarged lymph node, referred to as an excisional biopsy.

The biopsy is performed in a hospital on an outpatient basis in an operating room. You are provided with general anesthesia prior to the surgery to make you sleep. A local anesthetic may also be injected to numb the site of the incision.

Once the lymph node is removed, a temporary drain tube is inserted and the wound is sutured, taped, or stapled. From start to finish, the biopsy can take anywhere from 30 to 60 minutes.

An excisional biopsy provides the lab with more tissue to evaluate and, as such, is more useful than tissue samples obtained through fine needle aspiration or core needle biopsy.

The biopsied tissue can then be thinly sliced, placed on a slide, and examined under the microscope to look for the pathological changes in cells consistent with SLL.

Although bone marrow biopsies are sometimes performed to check the extent of the disease in bone marrow, they are not commonly used for the diagnosis of SLL.

Differential Diagnoses

Because the features of SLL are similar to those of other diseases (including many different types of lymphoma), healthcare providers will typically perform a differential diagnosis to exclude other possible causes. This typically includes investigations for:

SLL Staging

Staging is the process used to categorize the severity of the disease in order to direct appropriate treatment. In the United States, small lymphocytic lymphoma staging is usually done with the Rai staging system, developed by Dr. Kanti Rai in 1975. (In Europe, an alternate system called the Binet classification is more commonly used.)

The Rai classification is broken down as follows:

  • Stage 0: Lymphocytosis only
  • Stage 1: Lymphocytosis and lymphadenopathy 
  • Stage 2: Lymphocytosis and splenomegaly or hepatomegaly
  • Stage 3: Lymphocytosis and anemia due to the infiltration of cancer cells into the bone marrow
  • Stage 4: Lymphocytosis and thrombocytopenia due to the infiltration of cancer cells into the bone marrow

How Is SLL Treated?

Given that the majority of people with SLL are asymptomatic and the disease is relatively slow-moving, many healthcare providers will take a "watch-and-wait" approach until certain symptoms arise.

This spares you from therapies that can cause harmful side effects and undermine your quality of life. Delaying treatment in asymptomatic people also doesn't inherently alter the course of the disease, particularly since most people with SLL are diagnosed late in life.

The treatment of SLL typically begins when B symptoms develop and interfere with your ability to perform daily activities. Treatment may also be indicated if the absolute lymphocyte count doubles within the span of 12 months. In addition, there may be other reasons to start treatment in an SLL patient, such as worsening anemia or thrombocytopenia, Rai stage 3 or 4, massive or enlarging splenomegaly, or enlarged or massive lymph nodes.

Small lymphocytic lymphoma treatment, when needed, may include:


Combination chemotherapy is effective in newly treated people as well as those who have relapsed after previous treatment. The drugs fludarabine and Cytoxin (cyclophosphamide) are usually the backbones of most chemotherapy regimens. The monoclonal antibody Rituxan (rituximab) may also be added to chemotherapy.

Targeted Therapy

Targeted therapies involve drugs that are able to recognize and kill cancer cells but leave normal cells untouched. With SLL, the drugs target different proteins on the surface of the cancer cells that affect cell growth.

Among the targeted drugs commonly used for SLL are Copiktra (duvelisib), Imbruvica (ibrutinib), Venclexta (venetoclax), and Zydelig (idelalisib).

Copiktra comes with a warning regarding a possible increased risk of death and serious side effects. If you are taking Copiktra, talk with your healthcare provider about the risk and benefits of treatment with Copiktra. In addition, discuss any questions or concerns you may have, including possible alternative treatments.

Stem Cell Transplant

Allogeneic stem cell transplants, involving the transfer of blood-forming stem cells from a healthy donor, are experimental treatments typically used in younger people who are at risk of dying. It is a high-risk procedure.

An individual is first exposed to high-dose radiation to kill all traces of cancer, after which stem cells are infused into the bloodstream to rebuild bone marrow. This is usually performed as part of a clinical trial and poses a risk of illness and death due to chronic graft versus host disease, also known as tissue rejection.

Stem cell transplants may also be considered for older people, typically in a milder version called reduced-intensity conditioning allogeneic stem cell transplantation, in which pretreatment with radiation is limited. This procedure is used to extend life and reduce symptoms rather than cure the disease.

Treating Refractory Disease

For people with refractory disease (meaning that cancer no longer responds to chemotherapy or targeted drugs), more aggressive treatments are needed. This may include potentially toxic drugs like Revlimid (lenalidomide) and Lemtrada (alemtuzumab), which are used when no other drugs are available.

Prognosis For SLL

Small lymphocytic lymphoma prognosis can vary by the genetic characteristics and speed of progression of the disease. Certain characteristics identified with flow cytometry/FISH (including IGHV gene mutations and the presence of CD38 protein) are associated with poorer outcomes.

With that being said, SLL is generally a slowly progressive disease, and many people can live well and normally for years without treatment. In the United States, the 5-year survival rate for small lymphocytic lymphoma is 87.5%. This means 87.5% of people with SLL will live 5 years or longer after diagnosis.

According to current data from the National Cancer Institute, the five-year survival rate for SLL in the United States is 86.1%.

Many people with SLL live for far longer. Some people diagnosed in their 60s and 70s could very well live normal life spans. Even if treatment is needed, the 10-year survival rate for small lymphocytic lymphoma hovers at around 84% if you do not relapse during the first five years.

A Word From Verywell

It can be extremely unnerving to be told you have SLL. Even if people tell you that SLL is a "slow-moving disease," the uncertainty of what lies ahead can cause extreme anxiety. This is perfectly normal.

As much as you may want to rush to treatment, take time to learn about the disease and what the lab reports mean. Doing so can reduce stress by allowing you to understand when treatment is needed and what to expect when treatment starts. It also gives you time to get yourself healthy and start exercising and eating better, so that you can better tolerate treatment physically and emotionally.

Building support systems, remaining in continuous medical care, and developing coping skills are the three elements needed to ensure a longer, healthier life with SLL or any other type of cancer.

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By James Myhre & Dennis Sifris, MD
Dennis Sifris, MD, is an HIV specialist and Medical Director of LifeSense Disease Management. James Myhre is an American journalist and HIV educator.