Chronic Lymphocytic Leukemia (CLL) is a cancer of the blood and bone marrow that progresses slowly. It originates from a type of white blood cell called a B-cell. Diffuse Large B-cell Lymphoma (DLBCL) is a common and aggressive cancer of the lymphatic system, also arising from B-cells. It is possible for the slow-growing CLL to transform into a more aggressive cancer that behaves like DLBCL.
The Process of Richter’s Transformation
The transformation from CLL to a more aggressive lymphoma is known as Richter’s Transformation or Richter’s Syndrome. This occurs when the original CLL cells undergo further genetic changes, causing them to grow and spread rapidly. It is a fundamental shift into a new disease, occurring in about 2-10% of people with CLL over their lifetime.
The biological basis for this change lies within the cells’ genetic code. Genes like TP53, MYC, and NOTCH1 can be affected. A mutation in the TP53 gene removes a natural brake on cell growth, while changes in the MYC gene can put cell division into overdrive. These acquired genetic abnormalities allow the transformed cells to multiply quickly. The rate of transformation is estimated to be between 0.5% and 1% per year for an individual with CLL.
Recognizing the Signs of Transformation
A feature of this transformation is the sudden onset of symptoms that are out of character for a person’s CLL. One of the most common indicators is the swift swelling of lymph nodes, a condition called lymphadenopathy. These enlarged, painless nodes can appear in the neck, armpits, or groin.
Beyond swollen lymph nodes, a group of symptoms known as “B symptoms” signals a possible transformation. These include unexplained fevers, drenching night sweats, and significant, unintentional weight loss.
A person may also experience a sudden decline in their general health, manifesting as increasing fatigue, shortness of breath, or dizziness. Another sign can be a feeling of fullness or discomfort in the abdomen, which may be caused by a rapidly enlarging spleen.
Confirmation and Diagnosis
To confirm a suspected transformation, diagnosis begins with blood tests, which might show a rapid increase in the enzyme lactate dehydrogenase (LDH) or elevated calcium levels. While suggestive, these markers are not definitive.
An imaging test like a positron emission tomography (PET) scan is often used. This scan uses a radioactive sugar tracer that is taken up by highly active cancer cells, revealing areas of aggressive growth.
The definitive step in diagnosing Richter’s Transformation is a tissue biopsy. This procedure involves surgically removing a piece of an enlarged lymph node for examination. A pathologist identifies the change from small CLL lymphocytes to the large, aggressive cells characteristic of DLBCL, confirming the diagnosis.
Treatment Strategies for Transformed CLL
Treatment for Richter’s Transformation is fundamentally different and more intensive than the therapies used for CLL. The standard initial treatment is a chemoimmunotherapy regimen known as R-CHOP. This combines chemotherapy drugs (cyclophosphamide, doxorubicin, vincristine, and prednisone) with the immunotherapy drug rituximab.
Newer targeted therapies that focus on specific molecular pathways within the cancer cells are an area of active research and may be used, often through clinical trials. In some cases, more advanced cellular therapies may be considered.
Allogeneic stem cell transplantation, which involves receiving stem cells from a donor, is an option that can lead to long-term remission for some patients. Another advanced option is CAR T-cell therapy, where a patient’s own immune cells are re-engineered to fight the cancer. Given the complexity of Richter’s Transformation, seeking care at a major cancer center with experience in this condition and access to clinical trials is recommended.