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Many people live a long time with CLL, but in general it is very hard to cure, and treating it right away, especially if it isn't causing problems, hasn't been shown to help people live longer. Because of this, and because treatment can cause side effects, doctors often advise waiting until the leukemia is progressing or causing bothersome symptoms before starting treatment.

If treatment is needed, some important factors to take into account include the person’s age and overall health, and prognostic factors such as the leukemia cells having a deletion in chromosome 17 or a TP53 gene mutation, or an unmutated version of the IGHV gene.

Initial treatment of CLL

If CLL needs to be treated, there are many options for first-line treatment ,? including targeted drugs, chemotherapy, immunotherapy, and different combinations of these. 

Some of the more common options for the first-line treatment of CLL include:

• A BTK inhibitor such as ibrutinib (Imbruvica), zanubrutinib (Brukinsa), or acalabrutinib (Calquence), either alone or with an anti-CD20 immunotherapy such as obinutuzumab (Gazyva) or rituximab (Rituxan, other brand names)
• Venetoclax (Venclexta) and ibrutinib 
• Venetoclax with either rituximab or obinutuzumab
• High-dose methylprednisolone and either rituximab or obinutuzumab
• Obinutuzumab alone?

For people whose CLL cells do not have a deletion in chromosome 17 or a TP53 gene mutation, another option might be chemoimmunotherapy, such as:

• Fludarabine, cyclophosphamide, and rituximab (FCR)
• Bendamustine and either rituximab or obinutuzumab
• Chlorambucil and obinutuzumab

Other drugs or combinations of drugs may also be used.

Radiation or surgery

If the only problem is an enlarged spleen or swollen lymph nodes in one part of the body, localized treatment with low-dose radiation therapy may be an option. Splenectomy (surgery to remove the spleen) is another option if the enlarged spleen is causing symptoms.

Stem cell transplant

It's not common, but some people who have very high-risk CLL (based on prognostic factors) may be referred for a stem cell transplant (SCT) early in treatment.

Second-line or later treatments for CLL

If the first treatment for CLL is no longer working, or if the leukemia comes back, another type of treatment often helps. The options are generally the same as with the first treatment (targeted drugs, immunotherapy, and possibly chemotherapy), although they will depend on what the first treatment was and how well it worked, as well as other factors such as a person's overall health.

If the response to the initial treatment lasted a long time (usually at least a few years), the same treatment might be used again. If the initial response wasn't long-lasting, using the same treatment isn't as likely to be helpful.

Many of the same drugs and combinations listed above (as well as others) may be options as second-line treatments. Targeted therapy drugs and monoclonal antibodies are commonly used, alone or in combination. Chemo drugs might also be an option for some people.

Other types of treatments might be options as well. For example, some people who've already had treatment might benefit from a type of immunotherapy known as CAR T-cell therapy.

At some point, a stem cell transplant may be an option for some people, especially if they have a type of CLL that's harder to treat, such as if the cells have a chromosome 17 deletion or a TP53 gene mutation.

Clinical trials of newer treatments might also be a good option at some point, especially if many treatments have been tried.

Treating complications of CLL

P?eople with CLL are at risk for a number of complications, including low blood counts, infections, and an increased risk of some more aggressive types of cancer. Treating the CLL itself might help with some of these. But sometimes other types of treatments might be needed as well.

Low blood cell counts and infections

CLL can sometimes cause serious problems with low blood counts and infections. These are discussed in Supportive or Palliative Care for Chronic Lymphocytic Leukemia.

Leukapheresis for very high white blood cell counts

Although it's rare, some people with CLL have very high numbers of leukemia cells in their blood when they're first diagnosed, which causes problems with their blood circulation. This is called leukostasis, and it needs to be treated right away. Sometimes a procedure called leukapheresis might be used to remove the white blood cells, although this isn't used very often.

To learn more, see Supportive or Palliative Care for Chronic Lymphocytic Leukemia.

Other cancers?

One of the most serious complications of CLL is a change (transformation) in the leukemia to a high-grade or aggressive type of non-Hodgkin lymphoma (NHL) called diffuse large B-cell lymphoma (DLBCL) or to Hodgkin lymphoma. This is known as Richter's transformation (or Richter's syndrome). Treatment is often the same as it would be for that type of lymphoma, and it might include a stem cell transplant, because these cancers are often hard to treat.

Less often, CLL may progress to prolymphocytic leukemia, which can be hard to treat. Some studies have suggested that certain drugs such as cladribine (2-CdA) and alemtuzumab may be helpful.

In rare patients with CLL, the leukemia transforms (changes) into acute lymphocytic leukemia (ALL). If this happens, treatment is likely to be similar to that used for patients with ALL. 

Acute myeloid leukemia (AML) is another rare complication in people who have been treated for CLL, especially with chemotherapy. Drugs such as chlorambucil and cyclophosphamide can damage the DNA of blood-forming cells. These damaged cells may go on to become cancer, leading to AML, which tends to be very aggressive and often hard to treat.