Chronic lymphocytic leukemia (CLL) is one of the most common types of leukemia in adults. It is a cancer that affects the blood and bone marrow, causing an abnormal increase in lymphocytes (a type of white blood cell). CLL is generally slow growing, and many people can live with the disease for years without needing treatment. However, at some point the disease will progress and require therapy. This article provides an overview of when treatment is recommended for CLL.
What is CLL?
CLL is a cancer of B-lymphocytes, a type of white blood cell that helps fight infection. In CLL, the bone marrow produces too many abnormal lymphocytes that don’t function properly. These cancerous cells crowd out healthy blood cells, leading to a range of symptoms and complications:
- Fatigue due to anemia (low red blood cells)
- Frequent or severe infections due to low normal white blood cells
- Easy bleeding or bruising due to low platelets
- Enlarged lymph nodes, spleen, or liver
CLL is generally slow growing, and many people don’t have symptoms in the early stages. The cancer cells accumulate gradually over months and years. Eventually the bone marrow is unable to produce enough healthy blood cells, and the disease begins to cause problems.
When is treatment needed for CLL?
Doctors use two main factors to determine when to start treatment for CLL:
- Disease symptoms and complications
- Disease progression
Disease Symptoms and Complications
Many people with early stage CLL don’t have any symptoms and may not need treatment for years. Doctors follow a “watch and wait” approach, with regular checkups and lab work to monitor the disease. Treatment is generally started if CLL begins causing bothersome symptoms or complications such as:
- Fatigue, weakness, shortness of breath (from anemia)
- Recurrent infections
- Night sweats, unexplained fever (suggestive of infection)
- Unintended weight loss
- Pain or fullness from an enlarged spleen or liver
- Swollen lymph nodes
- Easy bruising or bleeding from low platelets
Starting treatment can help relieve symptoms and prevent complications like severe infections.
Disease Progression
Doctors also monitor for signs that the CLL is advancing and becoming more aggressive. Even without symptoms, treatment may be recommended if tests show:
- Worsening blood cell counts (anemia, low platelets)
- Significant or rapid increase in lymphocyte count
- Enlargement of lymph nodes, spleen or liver
- Changes in the cells indicating a more dangerous form of CLL
Starting treatment before symptoms appear can help slow the disease progression and prevent future complications.
Tests to Determine if Treatment is Needed
To monitor for disease progression and determine if treatment is needed, doctors utilize tests such as:
Complete Blood Count (CBC)
This common blood test measures levels of white blood cells, red blood cells, and platelets. Doctors look for dropping blood cell counts that could lead to symptoms and complications:
- Low red blood cell count (anemia)
- Low platelet count (increased risk of bleeding)
- Increasing white blood cell count, particularly lymphocytes (worsening CLL)
Physical Exam
During the physical exam, doctors check for enlarged lymph nodes, spleen or liver, which can indicate worsening CLL.
Imaging Tests
CT scans and ultrasound exams help detect abnormal enlargement of lymph nodes, spleen or liver. PET scans may also help identify areas where CLL is active.
Bone Marrow Biopsy
Examining bone marrow cells under the microscope provides information about the extent of CLL in the marrow and whether the cells have undergone any risky changes.
When to Start Treatment
The International Workshop on CLL provides guidelines on when treatment should start based on clinical stage, including:
Stage 0
Only Rai stage 0 or Binet stage A:
- Lymphocyte count increasing rapidly or higher than 50,000/μL
- Anemia (low red blood cells) or thrombocytopenia (low platelets) developing
- Symptomatic splenomegaly (enlarged spleen), lymphadenopathy (swollen lymph nodes), or other CLL-related symptoms
- Evidence of disease transformation to more aggressive lymphoma
Stage I-II
Rai stages I-II or Binet stages A-B:
- Rapid lymphocyte doubling time (< 6 months)
- Massive or progressive splenomegaly, lymphadenopathy, organomegaly or constitutional symptoms
- Progressive anemia or thrombocytopenia unresponsive to corticosteroids
- Disease transformation to aggressive lymphoma
Stage III-IV
Rai stages III-IV or Binet stage C:
- Treatment is recommended
First-Line Treatment Options
Once the decision is made to begin treatment, there are several standard initial (first-line) therapies for CLL:
Chemoimmunotherapy
This combines traditional chemotherapy drugs with immunotherapy drugs like rituximab (Rituxan). The regimen fludarabine, cyclophosphamide and rituximab (FCR) is a common option for younger, healthier patients.
Targeted Drug Therapy
Drugs that target specific proteins on cancer cells can disrupt cell growth and survival. Common options include ibrutinib (Imbruvica), idelalisib (Zydelig) and venetoclax (Venclexta).
Steroids
Steroid drugs like prednisone may be used alone or with other treatments. Steroids help reduce lymph node swelling and improve blood counts.
Radiation
For localized swollen lymph nodes or an enlarged spleen causing symptoms, targeted radiation may be used.
Stem Cell Transplant
A stem cell transplant may be an option for younger, healthier patients with high-risk or progressive CLL.
Second-Line Treatment
If the initial CLL treatment stops working or the disease relapses, there are additional therapies that can be used:
- Alternative chemoimmunotherapy regimens
- Different targeted drugs and drug combinations
- Experimental drug trials
- Chimeric antigen receptor (CAR) T-cell therapy
The choice of second-line treatment depends on the previous therapy used and a patient’s age, health status, and disease characteristics.
Conclusions
The key points to remember about starting treatment for CLL include:
- Many patients don’t need treatment for years until the disease advances
- Treatment often begins once patients have CLL-related symptoms or complications
- Worsening blood counts, lymph node/organ swelling and disease transformation also prompt treatment
- Regular monitoring helps doctors determine when to start therapy
- Powerful treatment options are available when needed
Starting treatment at the appropriate time enables patients to manage CLL effectively and enjoy prolonged remissions. By working closely with their medical team, patients can understand when treatment is recommended based on their individual disease characteristics and progression.