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Childhood Acute Lymphoblastic Leukemia


Acute lymphoblastic leukemia in children is a malignant disease or cancer of the blood characterized by the rapid uncontrolled growth of abnormal, immature white blood cells known as lymphoblasts. Acute lymphoblastic leukemia is the most common leukemia in children, with approximately 3,000 new patients diagnosed each year in the United States.

Progress in treating childhood ALL is attributed to risk-based therapy which was initiated three decades ago.1 Risk-based therapy means administering more treatment to children at high risk of relapse and less therapy to those at lower risk to avoid long-term side effects. Therefore, it is important to understand what features constitute high, intermediate and low risk of relapse for planning successful treatment. According to recent analyses and computer modeling, current treatment strategies for children with ALL treated between 2005 and 2009 should result in a 10-year survival of approximately 88%.2

A variety of factors ultimately influence a patient’s decision to receive treatment of cancer. The purpose of receiving cancer treatment may be to improve symptoms through local control of the cancer, increase a patient’s chance of cure, or prolong a patient’s survival. The potential benefits of receiving cancer treatment must be carefully balanced with the potential risks of receiving cancer treatment.

The following is a general overview of the treatment of childhood ALL. Treatment of adolescents and very young adults with ALL is often carried out using pediatric protocols because of data suggesting better outcomes for this group than when treatment is administered on adult protocols.3 Treatment of adults with ALL is included in a separate section: Adult Acute Lymphoblastic Leukemia.

Circumstances unique to your situation and prognostic factors of your cancer may ultimately influence how these general treatment principles are applied. The information on this website is intended to help educate you about your treatment options and to facilitate a mutual or shared decision-making process with your treating cancer physician.

Most new treatments are developed in clinical trials. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Participation in a clinical trial may offer access to better treatments and advance the existing knowledge about treatment of this cancer. Clinical trials are available for most stages of cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. To ensure that you are receiving the optimal treatment of your cancer, it is important to stay informed and follow the cancer news in order to learn about new treatments and the results of clinical trials.

Most children in the U.S. with ALL receive treatment through government-sponsored clinical trials on protocols designed by the Children’s Oncology Group (COG). These studies frequently evaluate more intensive therapy for children at high risk of treatment failure and less intensive therapy for lower-risk patients. It is important that children be treated on these clinical studies whenever possible in order to ensure that all of the therapy is correctly administered and to further the knowledge of treatment of childhood ALL. More information is available at the COG web site at http://www.childrensoncologygroup.org/. More information about treatment of childhood ALL on protocols sponsored by the National Cancer Institute can also be accessed at http://www.cancer.gov/.

Prior to determining the optimal treatment of childhood ALL patients are assessed for risk factors to determine the current protocol that is most appropriate to direct treatment. These risk factors include:

  • Age: Age at diagnosis is very important. Children who develop ALL in the first year of life have a very poor prognosis, especially if their leukemia cells contain a mutated gene called MLL. Children over the age of nine also have a relatively poor prognosis.
  • White Blood Cell Count (WBC): A WBC at diagnosis of 50,000 per microliter is associated with a poor prognosis and is often associated with other poor risk factors.
  • Central Nervous System (CNS) Involvement: All patients will have a spinal tap to determine presence or absence of leukemia. Presence of leukemia is a poor prognostic sign.
  • Gender: Males tend to have a worse outcome than females following treatment.
  • Leukemia Morphology: It is important to determine whether the leukemia is of T or B-cell origin. These studies are performed by examining bone marrow obtained under local anesthesia by a needle aspiration from the hip bone.
  • Immunophenotyping: 80-85% of childhood ALL cases are classified as having precursor B-cell ALL. There are three subtypes of precursor B-cell ALL and three quarters of these are classified as common precursor B-cell ALL which denotes a good prognosis. Other subtypes have a worse prognosis.
  • Cytogenetics: Cytogenetics (evaluation of chromosomes) will be performed on leukemia cells obtained from the bone marrow. There are a multitude of different cytogenetic abnormalities associated with childhood ALL. Some cytogenetic abnormalities are associated with a poor prognosis, such as the Philadelphia chromosome, but some are associated with a good prognosis. One extra chromosome (trisomy) or higher than normal chromosome numbers (hyperdiploidy) is associated with an improved survival.
  • After the initiation of treatment the rapidity of response as measured by bone marrow response on days 7 and 14 of treatment has prognostic significance.  Patients who have a slow or no clearing of leukemia blasts from the bone marrow by day 14 or 15 after initiation of treatment have a poor prognosis and are often assigned more aggressive treatments.4,5

Based on the above considerations patient are assigned a risk category. For example, standard risk would be a child 1-9 years old, with a WBC less than 50,000, a B-cell phenotype, absence of CNS involvement, absence of adverse cytogenetic abnormalities such as the Philadelphia chromosome, and bone marrow clearing of leukemia on days 7 and 14 following initiation of treatment.

It is important to realize that prognostic groups are constantly changing as treatment regimens change, For example, more aggressive treatment regimens can overcome some adverse risk factors. In addition, newer genetic tests may be able to more accurately predict outcomes of children with ALL. In one study gene profiling was used to identify eight types of pediatric ALL, which represents 90% of all cases. These eight types have distinct biologic characteristics and predicted response to therapy.6,7 Gene profiling promises to be a significant method for identifying patients with aggressive or non-aggressive malignancies and should ultimately assist in disease management. These studies, however, require stored cells and it is important for all patients and clinicians to be aware of the importance of having tumor banks where future genetic studies can be correlated with clinical outcomes.

A recent review article summarizes the current strategies for drug treatment of children with ALL.8 The treatment of childhood ALL is carried out in two phases. The initial treatment phase is called remission induction and the goal of remission induction therapy is to achieve a complete remission or disappearance of all detectable leukemia cells in the peripheral blood and bone marrow. After a complete remission is achieved, the second phase of treatment, called post-remission therapy, begins. Post-remission therapy is necessary because despite achieving a complete remission of leukemia with induction treatment, hidden undetectable leukemia cells still exist and the leukemia will return without additional post-remission therapy. Post-remission therapy is often referred to as consolidation. The intensity of post-remission therapy is dictated by risk factors for relapse as outlined above.


1 Trigg ME, Sather HN, Reaman GH, Ten year survival of children with acute lymphoblastic leukemia: a report from the Children’s Oncology Group. Leukemia Lymphoma 2008;49:1142-1154.

2 Pute D, Gondos A, Brenner H, Trends in 5- and 10-year survival after diagnosis with childhood hematologic malignancies in the United States, 1990-2004. Journal of the National Cancer Institute 2008; early on-line publication on September 9.

3 Boissel N, Auclerc M-F, Lhéritier V, et al. Should adolescents with acute lymphoblastic leukemia be treated as old children or young adults? Comparison of the French FRALLE-93 and LALA-94 trials. Journal of Clinical Oncology. 2003;21:774-780.

4 Sandlund J, Harrison P, Rivera G, et al. Persistence of lymphoblasts in bone marrow on day 15 and days 22 to 25 of remission induction predicts a dismal treatment outcome in children with acute lymphoblastic leukemia. Blood. 2002:100;43-47.

5 Coustan-Smith E, Sancho J, Behm F, et al. Prognostic importance of measuring early clearance of leukemic cells by flow cytometry in childhood acute lymphoblastic leukemia. Blood. 2002:100;52-58. Prepublished online April 17, 2002; DOI 10.1182/blood-2002-01-0006.

6 Mosquera-Caro M, Helman P, Veroff R, et al. Identification, Validation, and Cloning of a Novel Gene (OPAL 1) and Associated Genes Highly Predictive of Outcome in Pediatric Acute Lymphoblastic Leukemia Using Gene Expression Profiling. Blood 2004;102:4a, Abstract #1.

7 Fine B, Stanulla M, Schrappe M, et al. Gene Expression Patterns Associated with Recurrent Chromosomal Translocations in Acute Lymphoblastic Leukemia. Blood 2004;103;1043-1049.

8 Pui C-H, Evans WE. Treatment of Acute Lymphoblastic Leukemia. New England Journal of Medicine 2006;354:166-178.

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Brooke Bott

Patient Story: Brooke Bott

“Even though I was going through something really difficult, I still smiled my way through it.”