Acute Lymphoblastic Leukemia (ALL)
Diagnosis & Staging

Updated: September 2010

Definition - What is ALL?

ALL is the most common type of cancer in children, though it also occurs at any age. In ALL, too many stem cells develop into lymphoblasts, which would ordinarily develop into mature lymphocytes. However, in ALL, these blasts do not ever fully develop. These abnormal cells are known as leukemic cells, and are not able to fight infection. As the number of leukemic cells increases in the blood and bone marrow, there is less room for healthy white blood cells, red blood cells and platelets. This may cause infection, anemia and easy bleeding. The cancerous leukemic cells can also spread to the central nervous system (brain and spinal cord), lymph nodes, spleen and liver. ALL is an aggressive, acute leukemia, and progresses rapidly without treatment. Modern combination chemotherapy protocols have made ALL highly treatable, with remission achieved in the majority of patients.

Symptoms

The early signs of ALL may be similar to the flu or other common diseases. Symptoms include:

• Weakness or feeling tired

• Fever

• Easy bruising or bleeding

• Petechiae

• Shortness of breath

• Weight loss or loss of appetite

• Bone or joint pain

• Painless lumps in the neck, underarm, stomach, or groin

Diagnosis

Many tests are used to establish ALL diagnosis. Tests include:

• Complete blood count: This basic test obtains an accurate count of all the different types of blood cells. The hallmark of leukemia is an overabundance of white blood cells (leukocytes), and in some cases, this may be the first sign that alerts the doctor to the presence of leukemia. Leukocytes may also be normal or low in number too. In acute lymphocytic leukemia, characteristic cells called “lymphoblasts” or simply ‘blasts’ appear in significant numbers.

• Bone marrow aspirate and biopsy: A needle is inserted into the hipbone to obtain a small piece of bone and sample of bone marrow. A pathologist examines the samples under a microscope and performs special studies to classify the leukemia according to cell type and other parameters.

• Cytochemistry and immunocytochemistry: Cytochemistry refers to using special stains and chemical reactions to differentiate between types of leukemia. Immunocytochemistry uses the same principle, employing antibodies to produce distinct color changes in the cell sample that allow the pathologist to identify the type of leukemia present.

• Immunophenotyping: Immunophenotyping classifies cells according to their immunologic characteristics. This test uses monoclonal antibodies to more accurately determine the type of leukemia. The presence or absence of certain antigens, called CD antigens, cell surface markers expressed by leukocytes, is very useful in determining cell lineage (whether the leukemia derives from T cells or B cells).

• Cytogenetics (chromosome analysis): In adult ALL, the role of cytogenetics in patient management has largely been centered on the presence of the Philadelphia (Ph) chromosome which usually arises from t(9;22) and results in BCR-ABL fusion. Other recurrent chromosomal abnormalities have been described in adult ALL, however, their frequency has been low and their prognostic relevance is not clear. Getting a complete chromosome analysis at ALL diagnosis provides important diagnostic and prognostic information.

• Molecular testing, including polymerase chain reaction testing: This test examines genes in the leukemia cell. The presence of certain genes, called oncogenes, can help diagnose precisely what form of leukemia is present. For example, in Ph positive ALL, an oncogene called BCR-ABL is often the determining factor in making a diagnosis.

• Lumbar puncture (spinal tap): In ALL, doctors need to look for leukemia cells in cerebrospinal fluid surrounding the brain and spinal cord. After part of the lower back is numbed, some of the spinal cord fluid is withdrawn using a needle, and examined microscopically for blast cells.

Risk Stratification

Risk stratification in ALL has played an important role in predicting outcome and searching for alternative therapy to high risk patients. Although the definition of high-risk is not uniform in different studies, in general it includes:

1. Age older than 35 years

2. White blood cell (WBC) count exceeding 50 X 109/L (and in some studies 30 X 10⁹/L) for B-lineage and 100 X 109/L for T-lineage ALL

3. Poor-risk cytogenetic abnormalities including t(9;22), t(4;11), t(1;19), complex karyotype with 5 or more chromosomal abnormalities, low hypodiploid/ near triploidy

4. Failure to achieve complete remission (CR) post first induction chemotherapy 

Any one of the above adverse factors put patients at higher risk of relapse with 5-year disease-free survival (DFS) ranging from 11-33%.

The information contained in these guidelines is a statement of consensus of Leukemia/BMT Program of BC professionals regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult these documents is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. Use of these guidelines and documents is at your own risk and is subject to the Leukemia/BMT Program of BC’s terms of use available at Terms of Use.