Richter’s syndrome is the rapid transformation of chronic lymphocytic leukemia (CLL) into a more aggressive form of cancer associated with a less favorable outlook.

Not everyone with CLL will develop Richter’s syndrome. If you do, your healthcare team will likely suggest starting immunochemotherapy or may recommend involvement in a clinical study.

Richter’s syndrome (also known as Richter’s transformation) is a rare complication of CLL and small lymphocytic lymphoma.

Richter’s involves a rapid or sudden change from a less aggressive CLL to a more aggressive lymphoma with an unfavorable outlook.

Richter’s syndrome is the transformation of CLL to a more aggressive form of lymphoma, most commonly diffuse large B-cell lymphoma, though it can also transform into Hodgkin’s lymphoma.

The exact cause of this change is unknown However, researchers have identified several potential risk factors that may increase the chances that CLL will change to Richter’s syndrome. You may be more likely to experience Richter’s transformation if you:

  • are 65 years old or older
  • are male
  • have genetic or biological changes or mutations such as TP53 mutation status or unmutated IGHV status
  • have biomechanical differences such as abnormal platelet counts or immunoglobulin counts
  • have had certain reactions to treatments such as stem cell transplant, radiation, and chemoimmunotherapy

If Richter’s transformation of CLL occurs, you may experience symptoms known as B symptoms. These typically include:

  • fever
  • drenching night sweats
  • rapid unexplained weight loss

If you have CLL and you experience any of these three symptoms, you should tell a member of your treatment team as soon as possible. They will likely want to run tests to find out whether Richter’s transformation has occurred.

Another sign of Richter’s syndrome is swelling of your lymph nodes. You may notice swelling in your neck, your groin, your abdomen, or other areas with lymph nodes.

Blood tests may show rapidly rising levels of lactate dehydrogenase (LDH), a marker of potential tissue damage.

You may also develop anemia, which can cause symptoms such as:

  • restless legs
  • tiredness
  • lethargy
  • chest pain
  • reduced exercise tolerance
  • shortness of breath, which often occurs during exertion
  • weakness

Currently, the most common initial treatment for Richter’s transformation of CLL is chemoimmunotherapy.

After the initial treatment, your doctor may recommend secondary chemotherapy regimens.

Researchers have begun several clinical trials of various advanced treatment options that may help improve the overall outlook for people who are experiencing Richter’s transformation.

Current trials are looking into the safety and effectiveness of:

  • immune checkpoint blockers
  • Bruton tyrosine kinase (BTK) inhibitors
  • venetoclax
  • combinations of bispecific antibodies
  • chimeric antigen receptor T cells

The life expectancy of someone with Richter’s transformation of CLL is low. With currently available treatments, the average life expectancy is 6–12 months after diagnosis.

Targeted therapies do not appear to have much impact. In a small 2017 study of 71 people with Richter’s syndrome, the average overall survival time of people who received novel treatments — BTK inhibitors or venetoclax — was 3.3 months.

One factor affecting the outlook is clonality, which is an instance when two tumors come from the same cell. About 80% of Richter’s syndrome is clonally related to the initial CLL.

Clonally related Richter’s syndrome has a median survival rate of 14 months, while the median survival rate for non-clonally related Richter’s syndrome is about 5 years.

Other known independent factors that decrease life expectancy in Richter’s transformation are:

  • Zubrod performance status greater than 1*
  • LDH levels greater than 1.5 times the upper limit of normal
  • low platelet counts
  • tumor size of 5 centimeters or larger
  • more than one previous therapy

If CLL transforms into Hodgkin’s lymphoma, the outlook improves, with an overall survival rate of about 13 years.

*Zubrod scale is a scale of 0–4 that doctors may use to assess how cancer is affecting your daily life. A score of 0 indicates that you maintain normal activity levels. A score of 4 indicates that you are unable to move around.

Richter’s syndrome occurs in 2–10% of people with CLL. It typically does not occur until 2–4 years after CLL diagnosis, but it can happen at the same time as the initial diagnosis or at any time during the course of the cancer.

Richter’s syndrome is an uncommon condition in which CLL transitions rapidly to a more aggressive form of cancer. It is often diagnosed 2–4 years after the initial CLL diagnosis, but it can happen at any time.

Symptoms typically include night sweats, fever, and rapid, unexplained weight loss. Doctors will likely conduct blood tests to check for this change.

Current treatments are relatively ineffective, but future clinical studies may find safe, effective treatment options.