Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, however, the bone marrow produces abnormal white blood cells. These cells crowd out the healthy blood cells, making it hard for blood to do its work. In acute lymphocytic leukemia (ALL), also called acute lymphoblastic leukemia, there are too many of specific types of white blood cells called lymphocytes or lymphoblasts. ALL is the most common type of cancer in children.
Possible risk factors for ALL include being male, being white, previous chemotherapy treatment, exposure to radiation, and for adults, being older than 70.
Symptoms of ALL include:
- Weakness or feeling tired
- Easy bruising or bleeding
- Bleeding under the skin
- Shortness of breath
- Weight loss or loss of appetite
- Pain in the bones or stomach
- Pain or a feeling of fullness below the ribs
- Painless lumps in the neck, underarm, stomach, or groin
Tests that examine the blood and bone marrow diagnose ALL. Treatments include chemotherapy, radiation therapy, stem cell transplants, and targeted therapy. Targeted therapy uses substances that attack cancer cells without harming normal cells. Once the leukemia is in remission, you need additional treatment to make sure that it does not come back.
Childhood Acute Lymphoblastic Leukemia Treatment
Childhood acute lymphoblastic leukemia (ALL) is a type of cancer in which the bone marrow makes too many immature lymphocytes (a type of white blood cell).
Childhood acute lymphoblastic leukemia (also called ALL or acute lymphocytic leukemia) is a cancer of the blood and bone marrow. This type of cancer usually gets worse quickly if it is not treated.
ALL is the most common type of cancer in children.
Leukemia may affect red blood cells, white blood cells, and platelets.
In a healthy child, the bone marrow makes blood stem cells (immature cells) that become mature blood cells over time. A blood stem cell may become a myeloid stem cell or a lymphoid stem cell.
A myeloid stem cell becomes one of three types of mature blood cells:
A lymphoid stem cell becomes a lymphoblast cell and then one of three types of lymphocytes (white blood cells):
In a child with ALL, too many stem cells become lymphoblasts, B lymphocytes, or T lymphocytes. These cells are cancer (leukemia) cells. The leukemia cells do not work like normal lymphocytes and are not able to fight infection very well. Also, as the number of leukemia cells increases in the blood and bone marrow, there is less room for healthy white blood cells, red blood cells, and platelets. This may lead to infection, anemia, and easy bleeding.
This summary is about acute lymphoblastic leukemia in children, adolescents, and young adults. See the following PDQ summaries for information about other types of leukemia:
Past treatment for cancer and certain genetic conditions affect the risk of having childhood ALL.
Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn’t mean that you will not get cancer. Talk with your child’s doctor if you think your child may be at risk.
Possible risk factors for ALL include the following:
Signs of childhood ALL include fever and bruising.
These and other signs and symptoms may be caused by childhood ALL or by other conditions. Check with your child’s doctor if your child has any of the following:
- Easy bruising or bleeding.
- Petechiae (flat, pinpoint, dark-red spots under the skin caused by bleeding).
- Bone or joint pain.
- Painless lumps in the neck, underarm, stomach, or groin.
- Pain or feeling of fullness below the ribs.
- Weakness, feeling tired, or looking pale.
- Loss of appetite.
Tests that examine the blood and bone marrow are used to detect (find) and diagnose childhood ALL.
The following tests and procedures may be used to diagnose childhood ALL and find out if leukemia cells have spread to other parts of the body such as the brain or testicles:
The following tests may be done on the tissue that is removed:
Certain factors affect prognosis (chance of recovery) and treatment options.
The prognosis (chance of recovery) depends on:
- Age at diagnosis, gender, and race.
- The number of white blood cells in the blood at diagnosis.
- Whether the leukemia cells began from B lymphocytes or T lymphocytes.
- Whether there are certain changes in the chromosomes or genes of the lymphocytes with cancer.
- Whether the child has Down syndrome.
- Whether leukemia cells are found in the cerebrospinal fluid.
- Weight at diagnosis and during treatment.
- How quickly and how low the leukemia cell count drops after the first or second phase of treatment.
Treatment options depend on:
- Whether the leukemia cells began from B lymphocytes or T lymphocytes.
- Whether the child has standard-risk or high-risk ALL.
- The age of the child at diagnosis.
- Whether there are certain changes in the chromosomes of lymphocytes, such as the Philadelphia chromosome.
- How quickly and how low the leukemia cell count drops after initial treatment.
For leukemia that relapses (comes back) after initial treatment, the prognosis and treatment options depend partly on the following:
- How long it is between diagnosis and when the leukemia comes back after initial treatment.
- Whether the leukemia comes back in the bone marrow or in other parts of the body.
Adult Acute Lymphoblastic Leukemia Treatment
Signs and symptoms of ALL may include the following:
- Weakness or fatigue.
- Fever or night sweats.
- Bruises or bleeds easily (i.e., bleeding gums, purplish patches in the skin, or petechiae [flat, pinpoint spots under the skin]).
- Shortness of breath.
- Unexpected weight loss or anorexia.
- Pain in the bones or joints.
- Swollen lymph nodes, particularly lymph nodes in the neck, armpit, or groin, which are usually painless.
- Swelling or discomfort in the abdomen.
- Frequent infections.
ALL occurs in both children and adults. It is the most common type of cancer in children, and treatment results in a good chance for a cure. For adults, the prognosis is not as optimistic. This summary discusses ALL in adults. (Refer to the PDQ summary on Childhood Acute Lymphoblastic Leukemia Treatment for more information about ALL in children.)
Incidence and Mortality
Estimated new cases and deaths from ALL in the United States in 2016:
- New cases: 6,590.
- Deaths: 1,430.
ALL presumably arises from malignant transformation of B- or T-cell progenitor cells. It is more commonly seen in children, but can occur at any age. The disease is characterized by the accumulation of lymphoblasts in the marrow or in various extramedullary sites, frequently accompanied by suppression of normal hematopoiesis. B- and T-cell lymphoblastic leukemia cells express surface antigens that parallel their respective lineage developments. Precursor B-cell ALL cells typically express CD10, CD19, and CD34 on their surface along, with nuclear terminal deoxynucleotide transferase (TdT), while precursor T-cell ALL cells commonly express CD2, CD3, CD7, CD34, and TdT.
It has been recognized for many years that some patients presenting with acute leukemia may have a cytogenetic abnormality that is cytogenetically indistinguishable from the Philadelphia chromosome (Ph1). The Ph1 occurs in only 1% to 2% of patients with acute myeloid leukemia (AML), but it occurs in about 20% of adults and a small percentage of children with ALL. In the majority of children and in more than one-half of adults with Ph1-positive ALL, the molecular abnormality is different from that in Ph1-positive chronic myelogenous leukemia (CML).
Many patients who have molecular evidence of the bcr-abl fusion gene, which characterizes the Ph1, have no evidence of the abnormal chromosome by cytogenetics. The bcr-abl fusion gene may be detectable only by fluorescence in situ hybridization (FISH) or reverse-transcriptase polymerase chain reaction (RT-PCR) because many patients have a different fusion protein from the one found in CML (p190 vs. p210). These tests should be performed, whenever possible, in patients with ALL, especially in those with B-cell lineage disease.
L3 ALL is associated with a variety of translocations that involve translocation of the c-myc proto-oncogene to the immunoglobulin gene locus t(2;8), t(8;12), and t(8;22).
Patients with ALL may present with a variety of hematologic derangements ranging from pancytopenia to hyperleukocytosis. In addition to a history and physical, the initial workup should include:
- Complete blood count with differential.
- A chemistry panel (including uric acid, creatinine, blood urea nitrogen, potassium, phosphate, calcium, bilirubin, and hepatic transaminases).
- Fibrinogen and tests of coagulation as a screen for disseminated intravascular coagulation.
- A careful screen for evidence of active infection.
A bone marrow biopsy and aspirate are routinely performed even in T-cell ALL to determine the extent of marrow involvement. Malignant cells should be sent for conventional cytogenetic studies, as detection of the Ph1 t(9;22), myc gene rearrangements (in Burkitt leukemia), and MLL gene rearrangements add important prognostic information. Flow cytometry should be performed to characterize expression of lineage-defining antigens and allow determination of the specific ALL subtype. In addition, for B-cell disease, the malignant cells should be analyzed using RT-PCR and FISH for evidence of the bcr-abl fusion gene. This last point is of utmost importance, as timely diagnosis of Ph1 ALL will significantly change the therapeutic approach.
Diagnostic confusion with AML, hairy cell leukemia, and malignant lymphoma is not uncommon. Proper diagnosis is crucial because of the difference in prognosis and treatment of ALL and AML. Immunophenotypic analysis is essential because leukemias that do not express myeloperoxidase include M0 AML, M7 AML, and ALL.
The examination of bone marrow aspirates and/or biopsy specimens should be done by an experienced oncologist, hematologist, hematopathologist, or general pathologist who is capable of interpreting conventional and specially stained specimens.
Prognosis and Survival
Factors associated with prognosis in patients with ALL include the following:
- Age: Age, which is a significant factor in childhood ALL and AML, may be an important prognostic factor in adult ALL. In one study, overall, the prognosis was better in patients younger than 25 years; another study found a better prognosis in patients younger than 35 years. These findings may, in part, be related to the increased incidence of the Ph1 in older ALL patients, a subgroup associated with poor prognosis.[5,6]
- CNS involvement: As in childhood ALL, adult patients with ALL are at risk of developing CNS involvement during the course of their disease. This is particularly true for patients with L3 (Burkitt) morphology. Both treatment and prognosis are influenced by this complication.
- Cellular morphology: Patients with L3 morphology showed improved outcomes, as evidenced in a completed Cancer and Leukemia Group B study (CLB-9251 [NCT00002494]), when treated according to specific treatment algorithms.[8,9] This study found that L3 leukemia can be cured with aggressive, rapidly cycling lymphoma-like chemotherapy regimens.[8,10,11]
- Chromosomal abnormalities: Chromosomal abnormalities, including aneuploidy and translocations, have been described and may correlate with prognosis. In particular, patients with Ph1-positive t(9;22) ALL have a poor prognosis and represent more than 30% of adult cases. Bcr-abl-rearranged leukemias that do not demonstrate the classical Ph1 carry a poor prognosis that is similar to those that are Ph1-positive. Patients with Ph1-positive ALL are rarely cured with chemotherapy, although long-term survival is now being routinely reported when such patients are treated with combinations of chemotherapy and Bcr-abltyrosine kinase inhibitors.
Two other chromosomal abnormalities with poor prognosis are t(4;11), which is characterized by rearrangements of the MLL gene and may be rearranged despite normal cytogenetics, and t(9;22). In addition to t(4;11) and t(9;22), compared with patients with a normal karyotype, patients with deletion of chromosome 7 or trisomy 8 have been reported to have a lower probability of survival at 5 years. In a multivariate analysis, karyotype was the most important predictor of disease-free survival.[Level of evidence: 3iiDii]
Late Effects of Treatment for Adult ALL
Long-term follow-up of 30 patients with ALL in remission for at least 10 years has demonstrated ten cases of secondary malignancies. Of 31 long-term female survivors of ALL or AML younger than 40 years, 26 resumed normal menstruation following completion of therapy. Among 36 live offspring of survivors, two congenital problems occurred.
Source: National Cancer Institute