Complications of CLL or CLL Treatment


CLL patients may be more susceptible to infections due to either the CLL itself and/or its treatment. A higher risk of infection is caused by

  • The inability of the person’s CLL cells to make antibodies needed to fight infections
  • The effect of chemotherapy, which causes reduced blood cell counts for certain infection-fighting white blood cells in the blood, specifically neutrophils and monocytes.

Because of the increased risk for infection, vaccination for pneumococcal pneumonia (repeated every 5 years) and a yearly flu vaccine is recommended. CLL patients should never receive live vaccines (such as the Zostavax vaccine – live shingles vaccine) but can receive Shingrix® because it is an inactivated shingles vaccine.

Antibiotic therapy is usually required to treat bacterial or fungal infections during the course of the disease.

People who get recurrent infections may also receive injections of immunoglobulin (gamma globulin) on a regular basis to correct the immune deficiency. This treatment is expensive, but it does decrease the frequency of infections in CLL patients with low levels of immunoglobulin in their blood.

CMV (cytomegalovirus) reactivation can occur in about 10 to 25 percent of patients with relapsed or refractory CLL treated with alemtuzumab. It is important to monitor for this potential problem during alemtuzumab therapy. Appropriate anti-infection prophylaxis and routine monitoring for early signs of infection should be considered when patients receive therapy with this particular drug.

Low Blood Cell Counts

Supportive care for CLL may include administering blood cell growth factors to improve low blood cell counts. The use of white blood cell growth factors may benefit patients who experience prolonged low white blood cell counts after treatment. Examples of white blood cell growth factors are

  • Granulocyte-colony stimulating factor (G-CSF) (filgrastim [Neupogen®] or pegfilgrastim [Neulasta®]) that can increase the number of neutrophils
  • Granulocyte macrophage-colony stimulating growth factor (GM-CSF) (sargramostim [Leukine®]) that can increase the number of neutrophils and monocytes.

Richter Transformation

In about 2 to 10 percent of people with CLL, the disease transforms into diffuse large B-cell lymphoma(DLBCL) or Hodgkin lymphoma during the course of their disease and treatment. This is known as “Richter transformation” or “Richter’s syndrome.” This syndrome is much more common in patients with IgHv-unmutated 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.

Patients with Richter transformation should be treated with chemoimmunotherapy regimens designed for DLBCL. Allogeneic stem cell transplantation can also be considered following a response to initial therapy.

Outcome for patients with Richter transformation is generally poor unless it is diagnosed before they received treatment for CLL.

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).

Autoimmune Cytopenias

The most frequent autoimmune cytopenias in CLL patients are as follows. Bone marrow tests are used to confirm the presence of these conditions.

  • Autoimmune hemolytic anemia (AIHA)
  • Immunemediated thrombocytopenia (also known as “immune thrombocytopenic purpura” [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 cellsand causes 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. The direct antiglobulin test (DAT, also known as the “direct Coombs test”) is used to identify the autoantibodies; however, most patients with AIHA have a negative DAT test result. In these cases, additional serum markers, such as low haptoglobin (a blood protein) and elevated reticulocyte (immature red blood cell) levels are required to make the diagnosis. Patients with advanced disease; high-risk factors, such as unmutated gene status; increased serum beta2 -microglobulin levels; and high expression of ZAP-70 are also more likely to develop AIHA. Less often, the antibody works against the platelets. This condition, called “immune thrombocytopenic purpura” (ITP), results in significantly decreased platelet counts.

The drugs prednisone, rituximab and cyclosporine are sometimes used to treat AIHA and ITP. Splenectomyshould be considered in cases where the patient does not respond to steroid therapy. The drugs romiplostim (Nplate®) and eltrombopag (Promacta®) are both FDA approved for the treatment of thrombocytopenia in patients with ITP that is resistant to other treatments.

Tumor Flare Reactions

Tumor flare is a painful enlargement of the lymph nodes that may be accompanied by elevated lymphocyte counts, enlarged spleen, low-grade fever, rash and bone pain. These reactions are commonly seen in CLL patients treated with lenalidomide (Revlimid®). Use of steroid medications to control the inflammation and antihistamines to manage the rash are recommended.

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, nonmelanoma 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 or myelodysplastic syndromes. 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 malignancies in CLL patients. These include

  • Older age (older than 60 years)
  • Male gender
  • Elevated levels of certain blood markers, such as beta2 -microglobulin, lactate dehydrogenase and serum creatinine.

It is important to follow up with your oncologist on a regular basis because of the increased risk of second cancers associated with CLL.



Information provided by Leukemia & Lymphoma Society.


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