eMedicine Specialties > Pediatrics: General Medicine > Oncology

Acute Lymphoblastic Leukemia

Author: Noriko Satake, MD, Assistant Professor, Department of Pediatrics, Section of Hematology/Oncology, University of California Davis School of Medicine, Davis Medical Center
Coauthor(s): Janet M Yoon, MD, Assistant Clinical Professor, Department of Pediatrics, Hematology/Oncology, University of California Davis Medical Center
Contributor Information and Disclosures

Updated: Jan 5, 2009

Introduction

Background

Acute lymphoblastic leukemia (ALL) is the most common malignancy diagnosed in children, representing nearly one third of all pediatric cancers. The annual incidence rate for acute lymphoblastic leukemia is 30.9 cases per million population. The peak incidence occurs in children aged 2-5 years. 

Although a few cases are associated with inherited genetic syndromes (ie, Down syndrome, Bloom syndrome, Fanconi anemia), the cause remains largely unknown. Many environmental factors (ie, exposure to ionizing radiation and electromagnetic fields, parental use of alcohol and tobacco) have been investigated as potential risk factors, but none has been definitively shown to cause acute lymphoblastic leukemia. Various viruses may be linked to the development of leukemia, particularly when prenatal viral exposure occurs in mothers recently infected with influenza or varicella. However, no direct link has been established between viral exposure and the development of leukemia.

Acute lymphoblastic leukemia may also occur in children with various congenital immunodeficiencies (ie, Wiskott-Aldrich syndrome, congenital hypogammaglobulinemia, ataxia-telangiectasia) that have an increased predisposition to develop lymphoid malignancies.

With improvements in diagnosis and treatment, overall cure rates for children with acute lymphoblastic leukemia now approach 80%.  Further refinements in therapy, including the use of risk-adapted treatment protocols, may improve cure rates for patients at high risk while limiting the toxicity of therapy for patients with a low risk of relapse. This article summarizes advances in the diagnosis and treatment of childhood acute lymphoblastic leukemia.

Pathophysiology

In acute lymphoblastic leukemia, a lymphoid progenitor cell becomes genetically altered and subsequently undergoes dysregulated proliferation, survival, and clonal expansion. In most cases, the pathophysiology of transformed lymphoid cells reflects the altered expression of genes whose products contribute to the normal development of B cells and T cells. Several studies indicate that leukemic stem cells are present in certain types of acute lymphoblastic leukemia.1,2

Frequency

United States

Annually, 2500-3500 children are diagnosed with acute lymphoblastic leukemia.

International

Throughout the world, the incidence rate is thought to be similar to that in the United States.

Mortality/Morbidity

Overall cure rates for children with acute lymphoblastic leukemia now approach 80%. The 4-year event-free survival (EFS) rate for high-risk patients is approximately 65%.

Race

The overall incidence of acute lymphoblastic leukemia varies among different racial groups within the United States. White children are more frequently affected than black children. 

Sex

Acute lymphoblastic leukemia occurs slightly more frequently in boys than in girls. This difference is most pronounced for T-cell acute lymphoblastic leukemia.

Age

The incidence of acute lymphoblastic leukemia peaks in children aged 2-5 years.

Clinical

History

Children with acute lymphoblastic leukemia (ALL) generally present with signs and symptoms that reflect bone marrow infiltration and extramedullary disease. Because leukemic blasts replace the bone marrow, patients present with signs of bone marrow failure, including anemia, thrombocytopenia, and neutropenia. Clinical manifestations include fatigue and pallor, petechiae and bleeding, and fever. In addition, leukemic spread may manifest as lymphadenopathy and hepatosplenomegaly. Other signs and symptoms of leukemia include weight loss, bone pain, and dyspnea.

Signs or symptoms of CNS involvement, even when it occurs, are rarely observed at the time of the initial diagnosis. The signs and symptoms include headache, nausea and vomiting, lethargy, irritability, nuchal rigidity, and papilledema. Cranial nerve involvement, which most frequently involves the seventh, third, fourth, and sixth cranial nerves, may occur. Also, leukemia can present as an intracranial or spinal mass, which causes numerous neurologic symptoms, most of which are due to nerve compression.

Testicular involvement at diagnosis is rare. However, if present, it appears as painless testicular enlargement and is most often unilateral.

Physical

Physical findings in children with acute lymphoblastic leukemia reflect bone marrow infiltration and extramedullary disease. Patients present with pallor caused by anemia and petechiae and bruising secondary to thrombocytopenia. They also have signs of infection because of neutropenia. In addition, leukemic spread may be seen as lymphadenopathy and hepatosplenomegaly.

Careful neurologic examination to look for CNS involvement is important because the treatment for leukemia with CNS involvement is different.

In male patients, testicular examination is necessary to look for testicular involvement of leukemia.

Causes

Although a small percentage of cases are associated with inherited genetic syndromes, the cause of acute lymphoblastic leukemia remains largely unknown.

More on Acute Lymphoblastic Leukemia

Overview: Acute Lymphoblastic Leukemia
Differential Diagnoses & Workup: Acute Lymphoblastic Leukemia
Treatment & Medication: Acute Lymphoblastic Leukemia
Follow-up: Acute Lymphoblastic Leukemia
Multimedia: Acute Lymphoblastic Leukemia
References
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References

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Further Reading

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Keywords

acute lymphocytic leukemia, acute lymphatic leukemia, acute lymphoid leukemia, ALL, pediatric cancer, childhood cancer, childhood malignancy, inherited genetic syndromes, lymphoblastic leukemia, leukemia, leukemic blasts, T cell, T-cell ALL, B cell, B-lineage ALL, BCR-ABL, MLL, high-risk ALL, exposure to ionizing radiation, exposure to electromagnetic fields, allogeneic hematopoietic stem cell transplantation, HSCT, bone marrow failure, anemia, thrombocytopenia, neutropenia, petechiae, bleeding, lymphadenopathy, hepatosplenomegaly, bone pain, Down syndrome, Fanconi anemia, Bloom syndrome, influenza, varicella, Wiskott-Aldrich syndrome, congenitalhypogammaglobulinemia, ataxia-telangiectasia

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Contributor Information and Disclosures

Author

Noriko Satake, MD, Assistant Professor, Department of Pediatrics, Section of Hematology/Oncology, University of California Davis School of Medicine, Davis Medical Center
Disclosure: Nothing to disclose.

Coauthor(s)

Janet M Yoon, MD, Assistant Clinical Professor, Department of Pediatrics, Hematology/Oncology, University of California Davis Medical Center
Janet M Yoon, MD is a member of the following medical societies: American Society of Pediatric Hematology/Oncology and Children's Oncology Group
Disclosure: Nothing to disclose.

Medical Editor

Stephan A Grupp, MD, PhD, Director, Stem Cell Biology Program, Department of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia; Associate Professor of Pediatrics, University of Pennsylvania
Stephan A Grupp, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Hematology, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Timothy P Cripe, MD, PhD, Professor of Pediatric Hematology/Oncology, University of Cincinnati; Director, Translational Research Trials Office, Department of Pediatrics, Cincinnati Children's Hospital Medical Center
Timothy P Cripe, MD, PhD is a member of the following medical societies: American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Samuel Gross, MD, Professor Emeritus, Department of Pediatrics, University of Florida; Clinical Professor, Department of Pediatrics, University of North Carolina; Adjunct Professor, Department of Pediatrics, Duke University
Samuel Gross, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Robert J Arceci, MD, PhD, King Fahd Professor of Pediatric Oncology, Professor of Pediatrics, Oncology and the Cellular and Molecular Medicine Graduate Program, Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine
Robert J Arceci, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, and American Society of Pediatric Hematology/Oncology
Disclosure: Nothing to disclose.

 
 
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