Click here to go to the home page.
The Leukemia/Bone Marrow Transplant Program of BC

Healthcare Professionals
Cancer Management Guidelines

Acute Lymphoblastic Leukemia (ALL)

Updated: May 2016


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.


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


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:

  • Age older than 35 years
  • 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
  • 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
  • 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%.


Patients with acute lymphoblastic leukemia usually require urgent treatment to reduce symptoms and return blood counts to normal. This is called complete remission. Once a remission is achieved, additional treatment is given to consolidate remission and help prevent recurrence.


Chemotherapy is the main treatment for all forms of leukemia. Chemotherapy targets fast-dividing cells by disrupting critical parts of the cell cycle. Since cancer cells divide faster than normal cells, more cancer cells than normal cells are killed. Of course, a significant number of normal cells are damaged, which causes the many familiar side effects of chemotherapy. Chemotherapy may be given by mouth (pills), intravenously through an IV or catheter, or into the cerebrospinal fluid (intrathecally). Most often, combinations of chemotherapy drugs are used to achieve the optimal therapeutic outcome.

Chemotherapy is usually given in cycles, sometimes starting with intensive induction treatment, which takes several weeks. This is followed by a few weeks without treatment, allowing the patient to recover from side effects, mostly related to lower blood counts. The sequence is then repeated. Patients who achieve initial remission require additional treatment, usually given over a period of years (in acute lymphoblastic leukemia) in order to prevent recurrence. Treatment for acute leukemia is intensive and usually requires hospitalization.

Chemotherapy for ALL usually is intensive, involves a number of agents given in repeated cycles over 2-3 years and requires hospitalization initially for induction chemotherapy.

The following is a common induction combination protocol:

  • L-asparaginase or PEG-L-asparaginase, daunorubicin , vincristine and prednisone

Other drugs that may be used include:

  • Doxorubicin, cytarabine, also known as cytosine arabinoside or ara-C, etoposide, teniposide, 6-mercaptopurine, Methotrexate, cyclophosphamide, dexamethasone

Other drugs that may be used include:

  • 6-thioguanine, also known as 6-TG, 6-mercaptopurine, also known as 6-MP (Purinethol)

Beyond Chemotherapy: Advances in Treating Leukemia

Stem Cell Transplantation 

Hematopoietic cell transplantation (HCT) and peripheral blood stem cell transplantation are therapeutic treatments that use stem cells (immature blood cells) to treat a patient's malignancy, or to repair diseased or defective bone marrow.  Transplants are sometimes performed early in the course of treatment to improve outcomes.  In some patients, they are utilized when other treatments are not working.

These transplant procedures include intensive chemotherapy with or without radiation to destroy the cancerous cells. This is followed by an infusion of healthy new stem cells, which have the ability to grow back into the bone marrow and begin making normal blood cells again.

If a patient receives stem cells from a matched donor (using related, unrelated or cord blood), the transplant is called allogeneic. Like other tissue transplants, allogeneic stem cell transplants require a genetic match between the donor and recipient.

In allogeneic transplants, the donor is preferably a sibling. Alternatively, a matched unrelated donor who has a similar genetic type may be used. In some cases, a patient’s own stem cells may be used. This is called an autologous (self) transplant. Autologous transplant has no role in the management of ALL and is not indicated anymore for this disease.

Non-myeloablative HCT

A new transplant procedure has been developed to treat patients with leukemia and myelodysplasia who are older or have underlying medical problems. Reduced-Intensity Conditioning Transplant (RICT) or Non-myeloablative HCT, also called “mini-HCT or “mini transplant,” involves less intensive chemotherapy and radiation treatments.

Researchers now understand that the immune cells created by the transplanted donor stem cells may recognize any remaining cancer cells in the patient as “foreign,” and kill them – thus helping to fight the cancer. This RICT /mini-HCT strategy is showing great promise for leukemia and many other cancers, and is being used to treat patients who are not eligible for full myeloablative allo-transplantation. The role of RICT and/or Non-myeloablative HCT for ALL is still experimental.

Radiation Therapy

Radiation therapy uses high-energy X-rays or other types of radiation to kill cancer cells. Radiation therapy is used for prophylaxis whole brain irradiation in ALL in combination with intrathecal chemotherapy. Also it has an important role as part of the conditioning regimens before allogeneic transplantation. In addition as for many other types of cancer, radiation therapy plays a role in palliation for end stage symptomatic patients with bulky disease causing discomfort, compression or pain.


Acute lymphoblastic leukemia (ALL) in adults is characterized by its high response rate to induction chemotherapy: multiagent chemotherapy induces remission in 74%-92% of ALL patients; however the majority will relapse and succumb to their disease leaving only 27%-40% of adult patients younger than 60 years to enjoy long-term disease-free survival (DFS). Research is still ongoing to improve the results of patients with adult ALL, this includes using new agents, applying pediatric protocols (same agents, same dose intensity), and using allogeneic stem cell transplantation.


Click images to enlarge.

ALL Treatment Algorithm


BCCA Chemotherapy Protocols and PPOs


Click images to enlarge.

Outcome by Treatment Type 1989-2005

Outcome Slide 1 Outcome Slide 2

Outcome Slide 3 Outcome Slide 4

Outcome by Karyotype

Outcome by Karyotype

Chemotherapy in Elderly ALL Patients

Elderly Slide 1 Elderly Slide 2

Elderly Slide 3 Elderly Slide 4

Elderly ALL Patients Treated Aggressively

Elderly Aggressive

T-Cell ALL

T-Cell Slide 1 T-Cell Slide 2


Please check back for associated publications.


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 patientís care or treatment. Use of these guidelines and documents is at your own risk and is subject to the Leukemia/BMT Program of BCís terms of use available at Terms of Use.

^ Top

Go to "About Our Services" Go to "For Patients and Families" Go to "For Healthcare Professionals"