Lymph node metastasis in cancer progression: molecular mechanisms, clinical significance and therapeutic interventions
What To Know About Chronic Lymphocytic Leukemia And Lymphocyte Counts
Chronic lymphocytic leukemia (CLL) affects cells that become lymphocytes. Monitoring the number of lymphocytes in the blood is important for many aspects of this form of cancer.
A healthy adult usually has lymphocyte counts between 1,000 and 4,800 lymphocytes per microliter (μl) of blood. By comparison, people who have CLL have at least 5,000 B cells per μl in the blood for a minimum of 3 months. B cells are a type of lymphocyte.
The bone marrow produces lymphocytes. They are present in the lymphoid tissue such as the thymus, spleen, and lymph nodes and they circulate in the blood.
This article discusses how CLL affects the levels of these cells and what that might mean for a person's outlook.
Not all individuals with CLL have symptoms. In some cases, the disease progresses slowly before symptoms develop. Therefore, doctors partly base the diagnosis of CLL on the level of lymphocytes in the blood.
There are two main types of lymphocytes: B cells and T cells. Both types of lymphocytes are part of the immune system and help the body fight viruses, bacteria, and other pathogens.
B-cell CLL affects the B cells and is the most common form of the disease.
Another rare form of cancer related to CLL that can develop as a result of uncontrollable B-cell growth is known as B-cell prolymphocytic leukemia. It typically occurs as a transformation or evolution of B-cell CLL.
T-cell prolymphocytic leukemia is another related, rare form of cancer that has a higher prevalence among males and older adults.
A normal lymphocyte range for adults is anywhere between 1,000 and 4,800 lymphocytes in 1 μl of blood. A diagnosis of CLL requires a lymphocyte level of greater than or equal to 5,000 B cells per μl of blood for a minimum of 3 months. Doctors refer to abnormally high lymphocyte levels as lymphocytosis.
When someone develops CLL, they have a higher level of lymphocytes. However, these cells do not work as they should, so they do not fight infection properly.
If a person's blood tests show an abnormally high lymphocyte count, they should consult a doctor. Depending on the underlying cause of the increased count, additional symptoms may occur.
For example, if high lymphocytes occur due to leukemia, the person may experience:
Although a high lymphocyte count can indicate CLL, it can also occur due to other conditions. In some cases, abnormally high lymphocyte levels can develop as a typical part of the body's response to an infection. For instance, a viral infection, such as the flu, may lead to increased lymphocytes.
Increased counts can also sometimes develop due to an inflammatory condition, such as Crohn's disease. In addition, high lymphocytes can also indicate other types of cancer, including multiple myeloma.
Although a lymphocyte level of at least 5,000 B cells helps doctors make a diagnosis, it does not appear to determine a person's outlook.
Instead, researchers use staging systems for this purpose. A standard staging system for CLL is the Rai staging system, in which a lower stage indicates a better outlook.
All stages include lymphocytosis. They also include the following:
CLL often progresses slowly. In many cases, the cancer is not curable, but treatment helps keep the symptoms at bay and slows the progression of the disease.
Not all people with CLL start treatment immediately after diagnosis. One factor in determining when to start treatment is the level of lymphocytes.
Research from 2017 shows that a 50% increase in lymphocytes in 2 months indicates that treatment is necessary. Another sign is the lymphocyte level doubling in less than 6 months.
The presence of symptoms of leukemia also indicates the need for treatment to start.
Doctors determine lymphocyte counts through a B- and T-cell screen. This test involves a blood draw to measure the level of lymphocytes.
A lymphocyte count is part of a complete blood count, which measures red blood cells and platelets, as well as white blood cells. Doctors often order a complete blood count to help diagnose various illnesses and infections.
After finding an abnormally high lymphocyte level, a doctor may order a peripheral blood smear. This test looks at the maturity and form of the blood cells, providing the doctor with more information on the cause of high lymphocytes.
If the doctor suspects cancer, they may order a bone marrow biopsy. This involves removing a small amount of bone marrow, often from the hip bone, and sending it to a laboratory for analysis. The size, shape, and other traits of the cells help doctors determine a diagnosis.
The outlook for people with CLL often depends on the stage.
According to the American Cancer Society, CLL is usually difficult to cure. However, people with CLL often live many years after their diagnosis.
The 5-year relative survival rate for people with CLL is 88.5%. This statistic means that 88.5% of people are likely to still be alive 5 years after their diagnosis.
It is important to note that survival rate statistics vary depending on a person's stage at diagnosis and treatment options. A doctor can talk with a person about their individual outlook.
The number of lymphocytes, a type of white blood cell, increases with certain types of cancers. Therefore, a lymphocyte count of at least 5,000 B cells per μl of blood indicates the possibility of chronic lymphocytic leukemia (CLL).
However, increased lymphocytes also occur with other conditions, such as infections and inflammatory diseases.
Not everyone with CLL will require immediate treatment, but when lymphocyte levels increase quickly, this may indicate an advanced stage of cancer and the need for prompt treatment.
What Is The Outlook For Chronic Lymphocytic Leukemia?
The 5-year relative survival rate for chronic lymphocytic leukemia (CLL) among adults ages 20 or older is 87%. Although the condition is typically incurable, a person can live with this form of leukemia for many years.
There are two types of chronic lymphocytic leukemia (CLL). The cells for each form are slightly different, but doctors can only tell them apart by testing them in a laboratory.
Slower-growing CLL occurs when there are too many lymphocytes. A person may not need treatment for some time.
Faster-growing CLL occurs when there are too many CLL cells in the blood, blocking typical cell production. It is typically more severe.
This article focuses on survival rates for CLL and the factors that can influence a person's life expectancy or outlook. It also discusses how to achieve an optimal quality of life with CLL.
Survival rates can give a person more information about the outlook for their condition and help them plan treatment and care. However, survival rates are only an estimate.
Survival rates for leukemia have improved significantly over the past 40 years. In the United States, the current 5-year relative survival rate for CLL in adults ages 20 years or older is 87%.
CLL accounts for around 38% of new leukemia cases in adults ages 20 years or older.
The stage of CLL is an important factor in life expectancy. However, other factors also have an effect.
Doctors talk about stages to indicate how far cancer has progressed in a person's body. However, as leukemia affects the blood, doctors cannot stage it in this way.
There are two systems for staging leukemia: the Rai system and the Binet system. In the United States, doctors more commonly use the Rai system, while the Binet system is more common in Europe.
In the Rai system, a person undergoes blood tests to check for cancer cells and determine the number of white blood cells (WBC) in the blood and bone marrow.
Alongside a physical exam, this information can indicate one of five stages for CLL:
A higher stage number means that CLL is impacting more of the body. A higher stage will often shorten a person's life expectancy.
Learn about how CLL symptoms can progress.
Other factorsOther factors that can affect survival rates include:
Treatment can help people manage CLL symptoms and improve their overall outlook. It also focuses on stopping or slowing down the spread of CLL.
Treatment options for CLL include:
After treatment, a person may experience periods of few or no symptoms of CLL. This is often known as remission.
Learn more about CLL treatments.
Although there is no cure for CLL, ongoing treatment may help a person live with the condition for a long time. There are several ways that someone who has CLL can support their health and well-being.
Follow-up careAttending all medical appointments is essential to managing any medication and treatment side effects. When a doctor examines an individual at regular appointments, they can check for signs that CLL may be returning and treat it as quickly as possible.
Lifestyle changesPeople with CLL may benefit from gentle exercise and following a balanced diet. No research confirms a direct link between exercise, diet, and CLL management, but they can help support their overall health.
SupportGetting emotional support and expressing feelings may help an individual with CLL. This may be from friends, family, or community groups.
In the United States, the American Cancer Society offers information on local support groups and information services.
Having correct information can give a person more control and understanding. Finding out as much as possible about CLL and asking a doctor any questions can help with decisions about treatment and care.
Below are answers to common questions about CLL.
Can a person live a full life with CLL?Some people live for many years after a CLL diagnosis. Receiving an accurate diagnosis and beginning treatment as early as possible may help improve a person's outlook.
Learn about how doctors diagnose CLL.
How will CLL affect quality of life?In the early stages, CLL may not significantly affect a person's quality of life. However, a 2023 study of people with CLL in Israel found that males had a better quality of life during active surveillance, while females reported a better quality of life during active treatment. Symptoms of CLL and treatments may affect each person differently.
Is CLL classed as terminal?Although CLL is not curable, the 5-year relative survival rate for CLL is around 87% for adults ages 20 or older. A person's doctor can provide them with more accurate information about their outlook according to their individual circumstances.
Doctors can very rarely cure CLL. However, survival rates for this cancer are generally positive, particularly with early diagnosis and treatment. Currently, around 87% of people ages 20 or older with CLL survive for at least 5 years following diagnosis.
Various treatments can help manage symptoms and slow the progression of the condition. A person can also ask their doctor about support that may be available to them.
Read this article in Spanish.
Co-Occurrence Of Del(6q), RPS15 May Drive Poor Prognosis In CLL
The findings support previous research suggesting that worse prognosis in patients with del(6q) is not solely a result of genomic instability or presence of multiple genetic alterations.
Patients with chronic lymphocytic leukemia (CLL) who have chromosome 6q deletion (del[6q]) may have a frequency of certain mutations that yield poor outcomes, suggest researchers.1
In a letter to the editor published in the American Journal of Hematology, researchers outlined their findings of a small sample set of patients with del(6q), a less frequent cytogenetic alteration found in patients with CLL. In addition to occurring as a secondary abnormality, del(6q) may also occur as the first and only cytogenetic alteration, they found.
Across del(6q) samples, the mutational landscape varied based on whether other cytogenetic alterations were present.Image Credit: © momius - stock.Adobe.Com
"Several studies have suggested an association of del(6q) with inferior outcomes, allocating these CLL cases in an intermediate-risk category, although other studies have shown no difference in outcomes," explained the researchers. "The recurrence of del(6q) in other B-cell malignancies strongly suggests that this region contains unidentified tumor-suppressor gene(s). Nevertheless, CLL patients harboring del(6q) remain poorly characterized at the molecular level, partly due to the low incidence of cases, the lack of a FISH-based routinely assessment of del(6q), and the co-occurrence with other abnormalities that masks their clinical and biological significance."
The group analyzed data from 38 patient samples with del(6q) from 4 hospitals—2 in the US, 1 in Italy, and 1 in Spain. In 15 samples, del(6q) was the sole abnormality identified, whereas 23 samples showed del(6q) as the one of multiple cytogenic alterations.
In their data set, time to first treatment (TTFT) for patients with del(6q) as the sole genetic abnormality was significantly shorter than that for a cohort of 317 controls but was similar to that of patients with additional cytogenetic abnormalities.
This finding, said the researchers, supports previous findings that worse prognosis, including shorter treatment-free survival, in patients with del(6q) is not solely a result of genomic instability or presence of multiple genetic alterations.2,3
Compared with the cohort of controls, who were representative of CLL characteristics, patients with del(6q) had several adverse factors, including being younger at diagnosis (median age, 61 years vs 72 years; P < .001) and having unmutated IGHV (75% vs 45.7%; P = .005).
Across del(6q) samples, the mutational landscape varied based on whether other cytogenetic alterations were present.
"Surprisingly, the most frequently mutated gene in del(6q)-only CLL patients was RPS15 (40%). RPS15 gene encodes for the ribosomal subunit S15, located in the short arm of chromosome 19. In treatment naïve CLL patients, RPS15 mutations are infrequent (~4%), but enriched at relapse or in high-risk subgroups such as del17p (~20%)," explained the researchers, noting that "Within the whole del(6q) cohort (N = 38),TTFT of patients harboring RPS15 mutations was shorter than the rest of del(6q) cases without this gene mutated and shorter than patients harboring RPS15 mutations in the control group, demonstrating the prognostic significance of the co-occurrence of del(6q) and RPS15 mutations."
In these patients, XPO1 and ATM also occurred at a higher frequency, each present in 20% of samples.
Among the 23 samples with del(6q) and other cytogenetic alterations, TP53 (35%), NOTCH1 (17%), and NFKBIE (17%) occurred most frequently.
References:
1. Carretero CP, González T, Álamo MQ, et al. Chronic lymphocytic leukemia patients with chromosome 6q deletion as the sole cytogenetic abnormality display a high frequency of RPS15 mutations and have a poor prognosis. Am J Hematol. Published online July 1, 2024. Doi:10.1002/ajh.27421
2. Audil HY, Hampel PJ, Van Dye DL, et al. The prognostic significance of del6q23 in chronic lymphocytic leukemia. Am J Hematol. 2021;96(6):e203-e206. Doi:10.1002/ajh.26168
3. Wang D-M, Miao K-R, Fan L, et al. Intermediate prognosis of 6q deletion in chronic lymphocytic leukemia. Leuk Lymphoma. 2011;52(2):230-237. Doi:10.3109/10428194.2010.542599
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