Chronic Leukemia

 

Leukemia is the cancer of different types of blood cells, including the bone marrow cells and the lymphatic system. Leukemia is the 7th most common type of cancer in India. In 2018, about 32,471 deaths occurred due to leukemia in India. According to Globocan 2018, the worldwide mortality rate of leukemia was 2.5 per 100,000 population.

About chronic leukemia

Chronic leukemia refers to the slowly progressing cancer that begins in the blood forming-tissues. This results in the production of large number of abnormal white blood cells, which enter the blood stream, but are not as functional as the normal cells. Depending on the type of white blood cells affected, chronic leukemia can be classified as chronic myeloblastic leukemia (CML) and chronic lymphocytic leukemia (CLL).

Chronic myeloblastic/myeloid/ myelogenous/ leukemia (CML) is a cancer that affects the myeloid cells in the bone marrow (spongy tissue inside the blood, which produces blood cells) and blood. Normally, myeloid cells produce platelets, red blood cells, and most types of white blood cells (except lymphocytes). The leukemia cells grow, divide, and build up in the bone marrow and enter the bloodstream. Overtime, these cells invade other parts of the body, such as the spleen. CML usually occurs in adults, and rarely occurs in children.

Chronic lymphocytic leukemia (CLL) is the cancer of blood and bone marrow, which affects the lymphocytes- the white blood cells that help fight infection. In this type of cancer, leukemia cells build up slowly, overtime, without presenting any symptoms for years. After some time, these cells can grow and invade other parts of the body, such as the spleen, lymph nodes and liver. CLL commonly affects older adults.

Causes/Risk factors

CML and CLL both occur due to a mutation in the DNA of the respective cells, which causes production of abnormal, ineffective blood cells.

In case of CML, this mutation can promote cancer development, by the following processes:

  • An abnormal chromosome develops: Certain chromosome parts may get exchanged with others, resulting in the development of an extra-short chromosome 22, called the Philadelphia chromosome. This chromosome is present in 90% of the individuals with CML.
  • A new gene is created in Philadelphia chromosome: A new gene is created in this chromosome which ultimately promotes cancer and allow blood cells to grow uncontrollably.
  • Produces too many diseased blood cells: In CML, too many white blood cells containing Philadelphia chromosome are produced, which does not allow the cells to grow and die normally. These cells crowd out the normal blood cells and damage the bone marrow.

There are several factors that may increase the risk of CML and CLL, including:

  • Older age (>70 years)
  • Being male (in case of CLL)
  • Exposure to chemicals, including certain herbicides and insecticides (in CLL)
  • Radiation exposure, such as radiation therapy for certain types of cancer (in CML)
  • Family history (in case of CLL, not CML)
  • Being white (in case of CLL)

Signs and symptoms

Chronic leukemia in initial stages is asymptomatic. But symptoms may develop for some patients, and include:

  • Fever
  • Fatigue
  • Night sweats
  • Weight loss
  • Pain or fullness below the ribs on left side

Symptoms such as easy bleeding, bone pain, and loss of appetite may indicate CML, whereas painless, enlarged lymph nodes and frequent infections may indicate CLL.

Diagnosis

The following tests are recommended to diagnose CML and CLL.

Blood tests: Complete blood cell count can help to count the number of lymphocytes and other blood cells. Blood chemistry tests can be performed to measure organ function, which may reveal certain abnormalities.

A high number of B cells (a type of lymphocyte) can indicate CLL. A test called immunophenotyping or flow cytometry can determine if the increased lymphocytes are caused due to CLL or other blood disorders. Flow cytometry also helps to analyse the leukemia cells and predict the aggressiveness of the cells.

Fluorescence in situ hybridization (FISH): This test examines the leukemia cells for genetic abnormalities. The presence of Philadelphia chromosome indicates CML. Genetic evaluation can also be done with polymerase chain reaction (PCR) test.

Bone marrow tests: These tests involve collection of bone marrow samples from the hip bone, which will be analysed in the laboratory. Bone marrow biopsy and bone marrow aspiration are commonly used to diagnose chronic leukemia.

Imaging tests: CT scan, MRI scan and PET scan are performed to determine the spread of the cancer, or to find a suspicious area that may be cancerous or to estimate the effectiveness of the current treatment.

Staging of CML and CLL

The stages indicate the extent or spread of cancer. Knowing the stage of the cancer helps to plan the treatment.

CML is classified into 3 phases - chronic phase, accelerated phase, or blastic phase, based on the number of immature white blood cells (or blast cells) and severity of the symptoms.

  • Chronic phase: <10% of cells in blood and bone marrow are immature white blood cells.
  • Accelerated phase: 10% to 19% of cells in blood and bone marrow are blast cells.
  • Blastic phase: >20% of cells in blood or bone marrow are immature white blood cells. Occurrence of fever, tiredness, and an enlarged spleen during this phase, is known as blast crisis.

CLL has the following stages:

  • Stage 0: Too many lymphocytes in blood, but no other symptoms of leukemia.
  • Stage I: Too many lymphocytes in blood and lymph nodes are larger than usual.
  • Stage II: Too many lymphocytes in blood; liver or spleen is larger than usual, and lymph nodes may be larger than normal.
  • Stage III: Too many lymphocytes and few red blood cells in blood. Lymph nodes, spleen, or liver may be larger than usual.
  • Stage IV: Too many lymphocytes, too few platelets and may be too few red blood cells in the blood. Lymph nodes, spleen, or liver may be larger than usual.

Treatment

Treatment for chronic leukemia depends on several factors, including the type of cancer, stage of cancer, onset of symptoms, overall health of the patient and patient’s preferences. Some cases of early-stage CLL may not receive treatment; doctors may opt to wait and monitor the condition closely until it progresses.

Below are the treatment options for CLL and CML:

  • Targeted drug therapy: In this therapy, drugs that attack the cancer cells by focusing on the aspect of the cells which allows them to grow uncontrollably are used. This is the initial treatment option for patients with CML.
  • Chemotherapy: This treatment involves using drugs to kill fat-growing leukemia cells. These drugs can be given orally (pills) or intravenously (injecting into a vein). Sometimes, chemotherapy is combined with targeted drug therapy, and other treatment options to treat aggressive chronic leukemia.
  • Immunotherapy: In this therapy the body’s immune system is boosted to fight the cancer. This treatment may help the immune system to identify cancer cells and/or train the immune cells to fight cancer cells.
  • Bone marrow transplant (or stem cell transplant): During the bone marrow transplant, high doses of chemo drugs are used to kill the stem cells (blood-forming cells) in the bone marrow, following which the healthy adult blood stem cells from a donor are infused into the blood. These healthy cells travel to the bone marrow and produce new, healthy blood cells to replace the leukemia cells. This treatment method is reserved for patients who haven’t benefited from other treatment options.
  • Clinical trials: Clinical trials are the experiments which study the latest treatment for diseases or new ways of using the existing treatments. Clinical trials may give a chance for the patients to try new treatments but cannot guarantee the treatment outcomes. The risks and benefits of the available clinical trials can be discussed with the doctor.

Prevention:

CLL and CML have very few known risk factors, hence there is no definite way to prevent chronic leukemia. Some types of cancer can be prevented by making lifestyle modifications and avoiding risk factors, but these may not be helpful in case of CML and CLL. The only possibly avoidable risk factor for CML is exposure to high dose radiations.

Prognosis

The prognosis and survival of CLL and CML depend on many factosrs, including the type of cancer, the stage of cancer, blood cell counts, patient’s age, overall health of the patient, chromosomal changes, treatments chosen and response to treatment. The 5-year survival rate of CML and CLL are about 69.20% and 85.10%, respectively.

References:

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Care Cancer Institute at Care Hospitals

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