Leukaemia



Last Review Date: December 30, 2018


Overview

In Australia about 2,300 adults and 200 children are diagnosed each year with leukaemia, a cancer of the white blood cells (WBCs). While exposure to radiation, benzene, and some anticancer drugs have been shown to increase the risk of developing leukaemia, and a few cases are associated with genetic disorders or rare viral infections, the cause of most leukaemias is not known.

What is it?

Bone marrow is responsible for the production of blood cells; red blood cells (RBC), platelets, and white blood cells (WBC). The earliest precursors of these are called blasts, which usually mature over several stages before being released into the circulation.

Leukaemia arises when one abnormal blood cell begins to continuously replicate itself. As they accumulate, the production of other normal blood cells are compromised. They might also affect other organs as they spread through the bloodstream.

Leukaemia is classified by how quickly it progresses and the type of WBC involved.
 

Acute leukaemia

Acute leukaemia is characterised by rapidly progressive disease, typically within days or weeks. It is usually composed of immature cells (blasts). 

Acute myeloid  leukaemia (AML)

  • AML affects predominantly older people but can affect people of all ages
  • It is characterised by production of large numbers of myeloid blasts, with impaired maturation to mature neutrophils, and replace other normal cells in the bone marrow.
Acute promyelocytic leukaemia (APL or APML)
  • APL is an important type of AML associated with a unique genetic abnormality t(15;17) and responds very well to specific types of chemotherapy.
  • The diagnosis must be made urgently as serious clotting and bleeding complications can occur early; treatment must be started as soon as possible.

Acute lymphocytic leukaemia (ALL)

  • ALL is the most common type of leukaemia in children, although it can affect people of all ages.
  • It is characterised by production of either B or T lymphocytes.
Chronic leukaemias

Chronic leukaemia progresses more slowly, typically over several months or years. It tends to be found in older patients and is usually composed of mature cells.
 

Chronic myelogenous leukaemia (CML)

Mature B-Cell neoplasms

Chronic leukaemia of lymphoid system have many features overlapping with lymphomas. Often, the general term “neoplasm” is used instead. The distinction between the two is generally that the leukaemia signifies the presence of abnormal cells in the peripheral blood, whereas lymphoma signifies predominant involvement in the lymph nodes. Lymphoma is discussed separately (see lymphoma)
  • Chronic lymphocytic leukaemia (CLL) (also known as small lymphocytic lymphoma (SLL)) is the most common leukaemia in Western countries. It consists of a clone of mostly small mature B lymphocytes. A diagnosis can be made by peripheral blood using flow cytometry. A bone marrow biopsy is usually only indicated if treatment is being considered. In some patients CLL progresses so slowly that treatment is never indicated, while in others progression to more aggressive lymphomas could occur. Careful monitoring is usually required. Treatment is commenced only if the patient is symptomatic and/or other bone marrow cell production is affected (e.g. anaemia). 
  • B-cell prolymphocytic leukaemia (B-PLL) is a rare neoplasm of B prolymphocytes affecting the peripheral blood, bone marrow and spleen.
  • Hairy cell leukaemia (HCL) is a rare neoplasm of small mature B-lymphocytes with characteristic “hairy” projections. It is usually very slowly progressive and responds well to specific treatments.
Mature T and NK cell neoplasms
  • T-cell prolymphocytic leukaemia, T-cell large granular lympocytic leukaemia, Aggressive NK cell leukaema and Sezary syndrome are rare neoplasms of the T-cell lineage involving one or more of peripheral blood, bone marrow, lymph nodes, liver, spleen and skin.
  • Many subtypes of T-cell lymphomas (see the section lymphoma for more details).

Signs and symptoms

Acute leukaemia is often diagnosed because the patient feels ill. They may have symptoms related to not having enough normal cells, such as:

  • Weakness, shortness of breath and anaemia due to a lack of red blood cells (which carry oxygen to the body's tissues).
  • Bleeding and bruising due to a lack of platelets (which are cell fragments that the body uses in the clotting process to plug holes in leaking blood vessels).
  • Recurrent infections due to a lack of normal infection fighting WBCs.

Those with acute leukaemia may also have signs and symptoms related to accumulations of immature white blood cells, such as: bone and joint pain; enlarged lymph nodes, spleen, liver, kidneys, and testicles; and headaches, vomiting, confusion, and seizures (when excess cells collect in the brain or central nervous system). They may also experience fever, weight loss, and night sweats.

Chronic leukaemias often progress slowly and may be found by the doctor during a routine check-up before any symptoms are noticed, or they may cause milder forms of the same symptoms noticed with acute leukaemia. The rate at which they progress depends on the patient. Some cases may be monitored for years before they require treatment, while others may be more aggressive. The abnormal cell that is producing the chronic leukaemia may also become unstable. Further changes in the cell may cause a blast crisis, leading to the production of only immature cells and a rapidly worsening condition.


Tests

Laboratory tests

Full blood count and differential
These are routine blood tests that are ordered to check the number and relative proportion of cell type (red blood cells (RBC), platelets, white blood cell (WBC)) in the blood stream. They can provide the first evidence that a person has leukaemia. Abnormal cell counts, such as elevated WBC or low RBC counts may be due to leukaemia or a variety of temporary or chronic conditions. However, blasts (very immature WBCs) are not normally seen in the blood. If they are present, some kind of leukaemia is likely, and follow-up testing is indicated. They are also used to monitor the effectiveness of treatment and to detect recurrence.


Find out about the Full Blood Count

Bone marrow aspiration/biopsy
Bone marrow exists as a matrix of fibrous supporting tissue, fluid, undifferentiated stem cells, and a mixture of blasts and maturing blood cells. If your doctor suspects leukaemia, he/she will often order a bone marrow aspiration and biopsy to actually look at the fluid and tissue in the marrow. A pathologist or haematologist then examines the marrow sample (bone and/or fluid) under the microscope, evaluating the number, size, and shape of each of the cell types, as well as the proportions of mature and immature cells. If leukaemia is present, the type and severity of the disease can be determined.

Flow cytometry
Leukaemic cells may appear similar under the microscope. Flow cytometry is able to examine the markers on a cell. Millions of cells can be analysed by this method. This helps to determine the cell types and number of abnormal cells.  

Cytogenetic analysis and/or fluorescent in situ hybridization (FISH)
These specialised genetic tests are used to investigate chromosomal abnormalities. It is important for diagnosis, classification, treatment decision, prognosis and monitoring of leukaemia. One example is t(15;17) for acute promyelocytic leukaemia where chromosome 15 and 17 are translocated (fused) together. 

Polymerase chain reaction (PCR)
This test uses DNA to detect specific changes that are associated with certain leukaemias. It is often used in conjunction with cytogenetics/FISH. Very small amount of disease can be detected using this technique, enabling monitoring of minimal residual disease (MRD), which can be important to guide treatment decisions. Examples are PML-RARA in acute promyelocytic leukaemia and BCR-ABL in chronic myelogenous leukaemia. 

Lumbar puncture (spinal tap)
This is sometimes performed to look for leukaemic cells in the cerebrospinal fluid (CSF), which usually circulates around the spinal cord and brain. This is particularly important for some leukaemias and to guide specific therapy as the conventional chemotherapy does not usually penetrate the CSF well.  
 

Non-laboratory tests

Computerised tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) scans are sometimes used to look for signs of the disease in other areas such as lymph nodes, liver and spleen. Other imaging scans may be used to evaluate the organ function such as heart, liver and kidneys.


Treatment

In general, cure and remission rates of leukaemia continue to improve for both children and adults.

Symptomatic treatment may include red blood cell and/or platelet transfusions and antibiotic therapy. If the spleen is too swollen, it may need to be surgically removed.

Specific treatment depends on the type, severity and symptoms. Chemotherapy is usually involved. Treatment may also involve targeted therapies which attack specific weaknesses in the leukaemic cells. The goals of treatment are to, if possible, kill all of the leukaemic cells, push the disease into remission, and to restore normal production of blood cells. Radiation therapy is sometimes employed to kill cells and to relieve pain. If leukaemia cells have migrated into the cerebrospinal fluid, chemotherapy drugs that are injected directly into the spinal fluid may be required.

In some cases, the patient’s own cells may be collected, frozen, and reintroduced after a course of chemotherapy to “clean” the abnormal cells - autologous stem cell transplant. Allogeneic stem cell transplants (using stem cells collected by peripheral blood or bone marrow from a compatible donor - most frequently a family member) are sometimes used to cure selected cases of leukaemia. Autologous or allogeneic stem cell transplants may be considered when other treatment regimens have failed to push the leukaemia into remission, or when the leukaemia has recurred.

Patients are encouraged to discuss with their treating doctor the various treatment options, including new treatments that might be available through clinical trials.


Related pages

On this site
Tests: FBC, differential
Conditions: Anaemia, haemochromatosis, lymphoma

Elsewhere on the web
Leukaemia Foundation
Healthdirect Australia: Leukaemia

MedlinePlus Health Information:
Childhood leukaemia
Adult acute leukaemia
Adult chronic leukaemia

 


References

WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, Fourth Edition
WHO Classification of Tumours, Volume 2
IARC WHO Classification of Tumours, No 2
Swerdlow, S.H., Campo, E., Harris, N.L., Jaffe, E.S., Pileri, S.A., Stein, H., Thiele, J., Vardiman, J.W. IARC