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Complications of CLL or CLL Treatment


People with CLL are more likely to get infections.  

  • Patients may receive antibiotics to treat bacterial infections. Antiviral medications may also be given to treat or prevent viral infections. People with repeated lung and/or sinus infections may also get injections (shots) of immunoglobulins regularly to help prevent new infections. 
  • For some patients who experience long periods of low white blood cell counts, doctors may prescribe a type of drug called a growth factor that helps the bone marrow make more white blood cells. Examples of white blood cell growth factors are filgrastim (Neupogen®), pegfilgrastim (Neulasta®) and sargramostim (Leukine®). 

Due to the high risk of infections in CLL patients, vaccination for pneumococcal pneumonia should be repeated every five years, and a yearly flu vaccination is also recommended. CLL patients should never receive live vaccines. For example, patients should not receive Zostavax®, a live shingles vaccine, but can receive the inactivated shingles vaccine called Shingrix®. COVID-19 vaccines are also recommended. Talk to your doctor for more information. 

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Richter Transformation

In about 2 percent to 10 percent of people with CLL, the disease transforms into something more complex. Of this small group, 95 percent may develop diffuse large-B cell lymphoma (DLBCL), and the other 5 percent may develop Hodgkin lymphoma. This is known as “Richter transformation” or “Richter’s syndrome.” This syndrome is much more common in patients with high-risk factors. These include advanced-stage CLL according to the Rai system assessment; deletion of the short arm of chromosome 17 (del[17p]), trisomy 12, TP53 or NOTCH1 mutations; and IGHV-unmutated CLL. 

Richter transformation generally occurs between two to six years after a diagnosis of CLL. Patients may have significantly enlarged lymph nodes and may experience fevers and weight loss. Lymphocyte masses may also develop in parts of the body other than the lymph nodes. This transformation is less common in patients who do not receive chemoimmunotherapy for treatment of their CLL. 

Patients with Richter transformation whose CLL has transformed into DLBCL are treated with regimens designed for DLBCL. Allogeneic stem cell transplantation can also be considered following a response to initial therapy.  

Standard Hodgkin lymphoma therapy is used for patients with Richter transformation whose CLL has transformed to Hodgkin lymphoma. With aggressive therapy, these patients tend to do better and may be cured of this condition (although not the underlying CLL).  

Some treatment responses have been reported in recent studies with the use of CAR T-cell therapy for CLL patients with Richter transformation. Treatment in a clinical trial should be considered for these patients. If remission is achieved, these patients should consider an allogeneic stem cell transplant, which is the only curative option. 

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Autoimmune Cytopenias

Autoimmune cytopenias are conditions in which the immune system attacks the blood cells. Autoimmune cytopenias occur in 4 percent to 10 percent of patients with CLL. The most frequent autoimmune cytopenias in CLL patients are: 

  • Autoimmune hemolytic anemia (AIHA) 
  • Immune-mediated thrombocytopenia (also known as “immune thrombocytopenic purpura” or ITP) 
  • Pure red blood cell aplasia (PRCA) 

AIHA is the most common form of autoimmune cytopenia. Patients who have AIHA produce antibodies that work against their own cells. These “autoantibodies” are usually directed against the patient’s red blood cells and cause them to be removed rapidly from the blood. The loss of these red blood cells can worsen the effects of already low red blood cell counts.  

Bone marrow tests may be helpful to confirm the presence of these conditions. The drugs prednisone, rituximab, and cyclosporine are sometimes used to treat AIHA and ITP. The drugs romiplostim (Nplate®) and eltrombopag (Promacta®) are both approved by the FDA for the treatment of ITP that is resistant to other treatments. Splenectomy may be considered for treatment of AIHA and ITP in patients who do not respond to drug therapy. 

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Tumor Flare Reactions

Tumor flare is a drug-related, painful enlargement of the lymph nodes that may be accompanied by elevated lymphocyte counts, an enlarged spleen, low-grade fever, and/or rash and bone pain. 

These reactions are commonly seen in CLL patients treated with lenalidomide (Revlimid®). Use of steroid medications to control inflammation and antihistamines to manage the rash are recommended. 

Tumor Lysis Syndrome 

Tumor lysis syndrome (TLS) is a potentially life-threatening condition that occurs when large amounts of tumor cells are killed at the same time by the cancer therapy, releasing their content into the bloodstream. Patients with very enlarged, “bulky” lymph nodes are considered at high risk for developing TLS, which is best managed if anticipated and TSL therapy is given before treatment for CLL begins. 

Treatment for TLS includes increased hydration, monitoring, and treatment of electrolyte imbalances and abnormal uric acid levels, and therapy with the drug rasburicase (Elitek®), as needed. When starting venetoclax (Venclexta®), it is important to monitor for TLS. 

Second Cancers

People with CLL have a higher risk than people in the general population of developing a second cancer. This may be due to abnormalities in immune function associated with the disease and to the use of chemotherapeutic agents, which can induce potentially long-lasting remissions but are also associated with prolonged immunosuppression. 

The second cancers that are seen most frequently in CLL patients are acute myeloid leukemia, myelodysplastic syndromes, melanoma, gastrointestinal cancer, breast cancer, lung cancer, non-melanoma skin cancer, prostate cancer, kidney cancer, bladder cancer, and head and neck cancers. 

Both treated and untreated people with CLL can develop acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). These complications are more common after treatment with fludarabine and cyclophosphamide (FC) or fludarabine, cyclophosphamide, and rituximab (FCR). 

Although all CLL patients should be counseled about their increased risk for developing a second cancer, studies indicate there are some factors that may help predict the development of other cancers in CLL patients.  

These include:  

  • Older age (older than 60 years) 
  • Males

It is important to follow up with your oncologist regularly because of the increased risk of second cancers associated with CLL. An annual comprehensive skin examination is also strongly recommended.  

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