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What is Richter's Syndrome?

When CLL Changes

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Updated April 29, 2014

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Richter’s Syndrome (RS), also known as transformation, is the conversion of chronic lymphocytic leukemia (CLL) to more aggressive diffuse large B cell lymphoma (DLBCL) or immunoblastic lymphoma (both types of non-Hodgkin lymphoma, or NHL). About 10% of patients with CLL will transform to RS. It is very unusual that you would experience Richter’s transformation at the same time as CLL is diagnosed. In fact, it most commonly occurs several years after diagnosis with CLL.

Signs and Symptoms of Richter’s Syndrome

If your CLL has transformed to DLBCL or immunoblastic lymphoma, you will notice a distinct worsening of your symptoms. The characteristics of RS include rapid tumor growth with or without extranodal involvement, that is, progression of the CLL to organs outside the lymph nodes.

You may experience:

  • Rapidly enlarging lymph nodes
  • Abdominal discomfort related to an enlarged spleen and liver (called hepatosplenomegaly)
  • Symptoms of low red blood cell count (anemia), such as feeling extra tired, pale skin, shortness of breath
  • Symptoms of low platelet count (thrombocytopenia), such as easy bruising and unexplained bleeding
  • Signs of extranodal involvement in unusual sites, such as brain, skin, gastrointestinal system, skin, and lungs

Risk Factors for Transformation

The risk of developing RS from CLL is not related to the stage of your leukemia, how long you have had it, or the type of response to therapy you have received. In fact, what actually causes the transformation is not understood by scientists.

Recently, some studies have revealed that patients whose CLL cells show a specific “marker” called ZAP-70 may have an increased risk of transformation. Other studies have suggested that younger CLL patients -- that is, those that are less than 55 years of age -- may have an increased risk as well.

Another theory is that it is the prolonged length of time that CLL patients have a depressed immune system causes the transformation. Scientists make this suggestion because other types of patients who have a decreased immune system for a long time, such as human immunodeficiency virus (HIV) patients or patients who have received organ transplants, also have an increased risk of developing NHL.

Whatever the case may be, it does not appear that there is anything you can do to cause or prevent your CLL from transforming.

Treatment and Prognosis of Richter’s Syndrome

Treatment of RS usually involves chemotherapy protocols that are commonly used for NHL. These regimens have typically produced overall response rates of about 30%. Unfortunately, the average survival with regular chemotherapy is less than six months after RS transformation.

In recent years, studies have investigated the use of Fludarabine chemotherapy protocols as they have been shown to improve outcomes in patients with complicated CLL. The average survival with this type of chemotherapy was increased to 17 months in one study.

Another recent study has looked at a conjugated monoclonal antibody called Yttrium-90 ibritumomab tiuxetan (Zevalin) in the treatment of RS, but patients experienced severe toxicities and no improved outcomes in their disease.

Some smaller studies have looked at the use of stem cell transplant to treat this population. Most of the patients in these studies had received a lot of prior chemotherapy. Of the types of stem cell transplants that were tested, non-myeloablative transplant had less toxicity, better engraftment, and a possibility of remission. Further studies will be needed to see if this is a viable option for RS patients.

The Future of Richter’s Syndrome

In order to improve survival in patients with RS, scientists need to gain a better understanding of what causes the transformation from CLL to occur. With more information about RS at a cellular level, better targeted therapies could be developed against those specific abnormalities. However, experts caution that since there are a number of complicated molecular changes associated with RS, there may not ever be a single “all-purpose” targeted treatment, and that any of these medications would likely need to be combined with regular chemotherapy to get their best effect.

In the meantime, patients who have had their CLL transform to RS are encouraged to enroll in clinical studies to help science learn more about this condition.

Source:

Yee, K. O’Brien, S. and Giles, F. “Richter’s Syndrome: Biology and Therapy” The Cancer Journal May/ June 2005, 11:3

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