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Acute Lymphoblastic Leukemia

  • Author: Karen Seiter, MD; Chief Editor: Emmanuel C Besa, MD  more...
Updated: Apr 22, 2016

Practice Essentials

Acute lymphoblastic leukemia (ALL) is a malignant (clonal) disease of the bone marrow in which early lymphoid precursors proliferate and replace the normal hematopoietic cells of the marrow. ALL is the most common type of cancer and leukemia in children in the United States. The image below shows pre–B-cell ALL.

Diagnostic workup of a patient with pre–B-cell acu Diagnostic workup of a patient with pre–B-cell acute lymphoblastic leukemia. Bone marrow aspiration revealed French-American-British L2 morphology.

See Chronic Leukemias: 4 Cancers to Differentiate, a Critical Images slideshow, to help detect chronic leukemias and determine the specific type present.

Also, see the Childhood Acute Lymphoblastic Leukemia: Diagnosis, Management, and Complications slideshow to help recognize and treat this disease and its associated complications.

Signs and symptoms

Signs and symptoms of ALL include the following:

  • Fever
  • Decreased neutrophil count
  • Signs and symptoms of anemia, such as pallor, fatigue, dizziness, palpitations, cardiac flow murmur, and dyspnea with even mild exertion
  • Bleeding (eg, from thrombocytopenia due to marrow replacement)
  • Disseminated intravascular coagulation (DIC) at diagnosis (about 10% of cases)
  • Palpable lymphadenopathy
  • Symptoms related to a large mediastinal mass (eg, shortness of breath), particularly with T-cell ALL
  • Bone pain (severe and often atypical)
  • Left upper quadrant fullness and early satiety due to splenomegaly (about 10-20% of cases)
  • Symptoms of leukostasis (eg, respiratory distress, altered mental status)
  • Renal failure in patients with a high tumor burden
  • Infections, including pneumonia
  • Petechiae (particularly on lower extremities) and ecchymoses
  • Signs relating to organ infiltration with leukemic cells and lymphadenopathy
  • Rashes from skin infiltration with leukemic cells

See Clinical Presentation for more detail.


Laboratory tests and other studies used in the workup for ALL include the following:

  • Complete blood count with differential
  • Coagulation studies
  • Peripheral blood smear
  • Chemistry profile, including lactic dehydrogenase, uric acid, liver function studies, and BUN/creatinine
  • Appropriate cultures (in particular, blood cultures) in patients with fever or other signs of infection
  • Chest x-ray
  • Computed tomography
  • Multiple-gated acquisition scanning
  • Electrocardiography
  • Bone marrow aspiration and biopsy (definitive for confirming leukemia)
  • Immunohistochemistry
  • Flow cytometry
  • Cytogenetics
  • Polymerase chain reaction
  • Gene expression profiling

See Workup for more detail.


Treatment of ALL may include the following:

  • Induction chemotherapy (eg, standard 4- or 5-drug regimen, ALL-2, or hyper-CVAD)
  • Consolidation chemotherapy
  • Maintenance chemotherapy
  • Intrathecal chemotherapy for central nervous system (CNS) prophylaxis
  • Supportive care (eg, blood products, antibiotics, growth factors)

Special considerations apply to the treatment of the following:

  • Mature B-cell ALL
  • Ph+ ALL
  • ALL in older children and younger adults
  • Relapsed ALL
  • ALL in patients with hyperuricemia or at high risk for tumor lysis syndrome

See Treatment and Medication for more detail.



Acute lymphoblastic leukemia (ALL) is a malignant (clonal) disease of the bone marrow in which early lymphoid precursors proliferate and replace the normal hematopoietic cells of the marrow. ALL may be distinguished from other malignant lymphoid disorders by the immunophenotype of the cells, which is similar to B- or T-precursor cells. Immunochemistry, cytochemistry, and cytogenetic markers may also aid in categorizing the malignant lymphoid clone.

The image below shows pre–B-cell ALL.

Diagnostic workup of a patient with pre–B-cell acu Diagnostic workup of a patient with pre–B-cell acute lymphoblastic leukemia. Bone marrow aspiration revealed French-American-British L2 morphology.

See also Pediatric Acute Lymphoblastic LeukemiaAcute Lymphoblastic Leukemia (ALL) Guidelines, and Acute Myelogenous Leukemia.



The malignant cells of acute lymphoblastic leukemia (ALL) are lymphoid precursor cells (ie, lymphoblasts) that are arrested in an early stage of development. This arrest is caused by an abnormal expression of genes, often as a result of chromosomal translocations. The lymphoblasts replace the normal marrow elements, resulting in a marked decrease in the production of normal blood cells. Consequently, anemia, thrombocytopenia, and neutropenia occur to varying degrees. The lymphoblasts also proliferate in organs other than the marrow, particularly the liver, spleen, and lymph nodes.



Less is known about the etiology of acute lymphoblastic leukemia (ALL) in adults compared with acute myelogenous leukemia (AML). Most adults with ALL have no identifiable risk factors.

Although most leukemias occurring after exposure to radiation are AML rather than ALL, an increased prevalence of ALL was noted in survivors of the Hiroshima atomic bomb but not in those who survived the Nagasaki atomic bomb.

Rare patients have an antecedent hematologic disorder (AHD) such as myelodysplastic syndrome (MDS) that evolves to ALL. However, most patients with MDS that evolves to acute leukemia develop AML rather than ALL.

Increasingly, cases of ALL with abnormalities of chromosome band 11q23 following treatment with topoisomerase II inhibitors for another malignancy have been described. However, most patients who develop secondary acute leukemia after chemotherapy for another cancer develop AML rather than ALL.



Acute lymphoblastic leukemia (ALL) is the most common type of cancer and leukemia in children in the United States. ALL accounts for 26% of all cancers in children up to 14 years of age, and for 75% of pediatric leukemia cases.[1]

In adults, this disease is less common than acute myelogenous leukemia (AML). Approximately 1000 new cases of ALL occur in adults each year. However, due to the fact that there are more adults than children, the number of cases seen in adults is comparable to that seen in children. ALL is slightly more common in males than in females.

Worldwide, the highest incidence of ALL occurs in Italy, the United States, Switzerland, and Costa Rica.



Only 20-40% of adults with acute lymphoblastic leukemia (ALL) are cured with current treatment regimens.

Patients with ALL are divided into three prognostic groups: good risk, intermediate risk, and poor risk.

Good risk criteria include the following:

  • No adverse cytogenetics
  • Age younger than 30 years
  • White blood cell (WBC) count of less than 30,000/μL
  • Complete remission within 4 weeks

Intermediate risk includes those whose condition does not meet the criteria for either good risk or poor risk.

Poor risk criteria include the following:

  • Adverse cytogenetics – Translocations t(9;22), t(4;11)
  • Age older than 60 years
  • Precursor B-cell WBCs with WBC count greater than 100,000/μL
  • Failure to achieve complete remission within 4 weeks

Patients with precursor B-cell ALL have an extremely poor prognosis. Essentially, following standard chemotherapy or autologous transplantation, long-term survival is not achieved. Several reports have indicated that some patients with precursor B-cell ALL and t(4;11) may have prolonged survival following allogeneic transplantation; therefore, this is the treatment of choice.

Immunophenotype effects on prognosis

Czuczman et al studied 259 patients treated with several Cancer and Leukemia Group B (CALGB) protocols for newly diagnosed ALL and found no significant difference in response rates, remission duration, or survival for patients expressing myeloid antigens versus those not expressing myeloid antigens.[2] B-lineage phenotype was expressed in 79% of patients; one third of these coexpressed myeloid antigens. Seventeen percent of patients demonstrated T-lineage ALL; one quarter of these coexpressed myeloid antigens.[2]

T-lineage ALL was associated with younger age, male sex, presence of a mediastinal mass, higher WBC count and hemoglobin level, longer survival, and longer disease-free survival. The number of T markers expressed also had prognostic significance. Patients expressing six or more markers had longer disease-free and overall survival compared with patients expressing three or fewer markers.

In a report by Preti et al, 64 of 162 patients with newly diagnosed ALL coexpressed myeloid markers.[3] Patients coexpressing myeloid markers were significantly older, had a higher prevalence of CD34 expression, and had a lower prevalence of common ALL antigen expression than patients without myeloid expression. A trend toward a decreased remission rate was observed for patients coexpressing myeloid markers (64%) relative to those who did not coexpress such markers (78%).[3] However, no significant effect on remission duration or overall survival was observed.

Chromosome number and prognosis

The effect of chromosome number on prognosis is displayed in Table 1, below.

Table 1. Effect of Chromosome Number on Prognosis (Open Table in a new window)

Chromosome Number 3-Year Event-Free Survival
Near tetraploidy 46-56%
Normal karyotype 34-44%
Hyperdiploidy >50 32-59%
Hyperdiploidy 47-50 21-53%
Pseudodiploidy 12-25%
Hypodiploidy 11%

Complications and prognosis

A study by Ness et al found neuromuscular impairments were prevalent in survivors of childhood ALL and these impairments interfered with physical performance.[4] Increased cumulative doses of intrathecal methotrexate and/or vincristine were associated with long-term neuromuscular impairments, and these have implications on future function with age.

The most common complication is failure of the leukemia to respond to chemotherapy. These patients do poorly, because they usually do not respond to other chemotherapy regimens.

Death in those with ALL may occur as a result of uncontrolled infection or hemorrhage. This may occur even after the use of appropriate blood product and antibiotic support.


Patient Education

Patients with acute lymphoblastic leukemia (ALL) should be instructed to immediately seek medical attention if they are febrile or have signs of bleeding. Furthermore, while receiving chemotherapy, patients with leukemia should avoid exposure to crowds and people with contagious illnesses, especially children with viral infections.

Although activity may occur as tolerated, patients with ALL may not participate in strenuous activities such as lifting or exercise. In addition, a neutropenic diet is recommended in these individuals, as follows:

  • No fresh fruits or vegetables may be eaten
  • All foods must be cooked
  • Meats are to be cooked until well done

For patient education information, see Blood and Lymphatic System Center and Cancer and Tumors Center, as well as Leukemia.

Contributor Information and Disclosures

Karen Seiter, MD Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College

Karen Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Hematology

Disclosure: Received honoraria from Novartis for speaking and teaching; Received consulting fee from Novartis for speaking and teaching; Received honoraria from Celgene for speaking and teaching.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Ronald A Sacher, MB, BCh, FRCPC, DTM&H Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MB, BCh, FRCPC, DTM&H is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society on Thrombosis and Haemostasis, Royal College of Physicians and Surgeons of Canada, American Clinical and Climatological Association, International Society of Blood Transfusion

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: GSK Pharmaceuticals,Alexion,Johnson & Johnson Talecris,,Grifols<br/>Received honoraria from all the above companies for speaking and teaching.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Clarence Sarkodee Adoo, MD, FACP Consulting Staff, Department of Bone Marrow Transplantation, City of Hope Samaritan BMT Program

Clarence Sarkodee Adoo, MD, FACP is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American Society of Hematology, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

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Diagnostic workup of a patient with pre–B-cell acute lymphoblastic leukemia. Bone marrow aspiration revealed French-American-British L2 morphology.
Diagnostic workup of a patient with pre–B-cell acute lymphoblastic leukemia. Flow cytometry shows that the cells were positive for CD10, CD19, CD22, CD34, and terminal deoxynucleotidyl transferase.
Table 1. Effect of Chromosome Number on Prognosis
Chromosome Number 3-Year Event-Free Survival
Near tetraploidy 46-56%
Normal karyotype 34-44%
Hyperdiploidy >50 32-59%
Hyperdiploidy 47-50 21-53%
Pseudodiploidy 12-25%
Hypodiploidy 11%
Table 2. Common Cytogenetic Abnormalities in ALL
Abnormality Genes Involved 3-Year Event-Free Survival
t(10;14)(q24;q11) HOX11/TCRA 75%
6q Unknown 47%
14q11 TCRA/TCRD 42%
11q23 MLL 18-26%
9p Unknown 22%
12 TEL 20%
t(1;19)(q23;p13) PBX1/E2A 20%








t(9;22)(q34;q11) bcr-abl 5-10%*


t(4;11)(q21;q23) AF4-MLL 0-10%
* Traditional regimens.

Hyper-CVAD (cyclophosphamide, vincristine, doxorubicin [Adriamycin], dexamethasone) with rituxan.

Hyper-CVAD with imatinib.

Table 3. Immunophenotyping of ALL Cells – ALL of B-Cell Lineage (85% of cases of adult ALL)
ALL Cells TdT CD19 CD10 CyIg SIg
Early B-precursor ALL + + - - -
Pre–B-cell ALL + + + + -
B-cell ALL - + +/- +/- +
ALL = acute lymphoblastic leukemia; Cylg = Cytoplasmic immunoglobulin; SIg =Surface immunoglobulin; TdT = terminal deoxynucleotidyl transferase.
Table 4. Immunophenotyping of ALL Cells – ALL of T-Cell Lineage (15% of cases of adult ALL)
ALL Cells TdT Surface CD3 CD4/CD8
Early T-precursor ALL + - +/+ or -/-
T-cell ALL + + +/- or -/+
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