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Acute Lymphocytic Leukemia



Acute Lymphocytic Leukemia

Also known as: Acute lymphoblastic leukemia or Acute childhood leukemia

Acute lymphocytic leukemia (ALL), is a form of leukemia, or cancer of the white blood cells characterized by excess lymphoblasts.

Malignant, immature white blood cells continuously multiply and are overproduced in the bone marrow. ALL causes damage and death by crowding out normal cells in the bone marrow, and by spreading (metastasizing) to other organs. ALL is most common in childhood with a peak incidence at 2-5 years of age, and another peak in old age. The overall cure rate in children is about 80%, and about 45%-60% of adults have long-term disease-free survival.

Acute refers to the relatively short time course of the disease (being fatal in as little as a few weeks if left untreated) to differentiate it from the very different disease of Chronic Lymphocytic Leukemia which has a potential time course of many years. It is interchangeably referred to as Lymphocytic or Lymphoblastic. This refers to the cells that are involved, which if they were normal would be referred to as lymphocytes but are seen in this disease in a relatively immature (also termed ‘blast’) state.

Contents

Signs and Symptoms
Causes
Diagnosis
Pathogenesis/Pathophysiology
Race and Ethnicity
Sex
Age
Prevention
Treatment
Complications
Prognosis
References

Signs and Symptoms

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Initial symptoms are not specific to ALL, but worsen to the point that medical help is sought. The signs and symptoms of ALL are variable but follow from bone marrow replacement and/or organ infiltration.

  • Generalized weakness and fatigue
  • Anemia
  • Frequent or unexplained fever and infections
  • Weight loss and/or loss of appetite
  • Excessive and unexplained bruising
  • Bone pain, joint pains (caused by the spread of “blast” cells to the surface of the bone or into the joint from the marrow cavity)
  • Breathlessness
  • Enlarged lymph nodes, liver and/or spleen
  • Pitting edema (swelling) in the lower limbs and/or abdomen
  • Petechiae, which are tiny red spots or lines in the skin due to low platelet levels
  • Bleeding from the gums
  • Frequent or severe nosebleeds
  • Pale skin

Causes

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ALL makes up 80% of childhood acute leukemias. Most cases occur in children ages 3 – 7. The disease may also occur in adults.

In acute leukemia, cancerous cells multiply quickly and replace normal cells. Cancerous cells take over normal parts of the bone marrow, often causing low blood counts.

Most cases of ALL have no obvious cause. However, the following may play a role in the development of leukemia:

  • Certain chromosome problems
  • Radiation exposure or being exposed to x-rays before birth
  • Past treatment with chemotherapy drugs
  • Receiving a bone marrow transplant
  • Toxins such as benzene

Persons with Down syndrome or other genetic disorders, or who have a brother or sister with leukemia are at increased risk for ALL.

Diagnosis

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Diagnosing ALL begins with a medical history and physical examination, complete blood count, and blood smears. Because the symptoms are so general, many other diseases with similar symptoms must be excluded. Typically, the higher the white blood cell count, the worse the prognosis. Blast cells are seen on blood smear in 90% of cases. A bone marrow biopsy is conclusive proof of ALL. A lumbar puncture (also known as a spinal tap) will tell if the spinal column and brain has been invaded.

Pathological examination, cytogenetics (particularly the presence of Philadelphia chromosome) and immunophenotyping, establish whether the “blast” cells began from the B lymphocytes or T lymphocytes. DNA testing can establish how aggressive the disease is; different mutations have been associated with shorter or longer survival. Immunohistochemical testing may reveal TdT or CALLA antigens on the surface of leukemic cells. TdT is a protein expressed early in the development of pre-T and pre-B cells while CALLA is an antigen found in 80% of ALL cases and also in the “blast crisis” of CML.

Medical imaging (such as ultrasound or CT scanning) can find invasion of other organs commonly the lung, liver, spleen, lymph nodes, brain, kidneys and reproductive organs.

Pathogenesis/Pathophysiology

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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.

Race and Ethnicity

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All races, but usually white or Hispanic are at higher risk.

Sex

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Usually male.

Age

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ALL is the most common cancer in children 1 to 7 years old. The incidence of ALL among 1- to 4-year-old children is nearly eight times greater than the rate for young adults 20 to 24 years.

Survival statistics have improved significantly over the past four decades. Most children under 19 with ALL will become five-year survivors of the disease.

Prevention

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Because the cause is usually unknown, it is not possible to prevent most cases. The risk of ALL can be reduce by avoiding exposure to toxins, radiation, and chemicals.

Treatment

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In general, treatment for acute lymphocytic leukemia falls into separate phases:

  • Induction therapy. The purpose of the first phase of treatment is to kill most of the leukemia cells in the blood and bone marrow.
  • Consolidation therapy. Also called post-remission therapy, this phase of treatment is aimed at destroying the leukemia cells remaining in the brain or spinal cord.
  • Maintenance therapy. The third phase of treatment prevents leukemia cells from regrowing. The treatments used in this stage are often given at much lower doses.
  • Preventive treatment to the spinal cord. People with acute lymphocytic leukemia may also receive treatment to kill leukemia cells located in the central nervous system during each phase of therapy. In this type of treatment, chemotherapy drugs are injected directly into the fluid that covers the spinal cord. This kills cancer cells that can’t be reached by chemotherapy drugs given by mouth or through an intravenous line.

Depending on the situation, the phases of treatment for acute lymphocytic leukemia can span 2 1/2 to 3 1/2 years.

Treatments may include:

  • Chemotherapy. Chemotherapy, which uses drugs to kill cancer cells, is typically used as an induction therapy for children and adults with acute lymphocytic leukemia. Chemotherapy drugs can also be used in the consolidation and maintenance phases.
  • Targeted drug therapy. Targeted drugs attack specific abnormalities present in cancer cells that help them grow and thrive. One targeted drug, imatinib (Gleevec), specifically attacks cancer cells that have a certain abnormality called the Philadelphia chromosome. The drug dasatinib (Sprycel) works in a similar way. These drugs are approved only for people with the Philadelphia chromosome-positive form of ALL.
  • Radiation therapy. Radiation therapy uses high-powered beams, such as X-rays, to kill cancer cells. If the cancer cells have spread to the central nervous system.
  • Stem cell transplant. A stem cell transplant may be used as consolidation therapy in people at high risk of relapse or for treating relapse when it occurs. This procedure allows someone with leukemia to re-establish healthy stem cells by replacing leukemic bone marrow with leukemia-free marrow. A stem cell transplant begins with high doses of chemotherapy or radiation to destroy any leukemia-producing bone marrow. The marrow is then replaced by bone marrow from a compatible donor (allogeneic transplant). In some cases, adults with ALL are able to use their own bone marrow for transplantation (autologous transplant). This may be possible if the patient has gone into remission and healthy bone marrow is then harvested for a future transplant.
  • Clinical trials. Clinical trials are experiments to test new cancer treatments and new ways of using existing treatments. While clinical trials the patient a chance to try the latest cancer treatment, treatment benefits are still being evaluated.

ALL in older adults

Older adults, such as those older than 65, tend to experience more complications from ALL treatments. And older adults generally have a worse prognosis than children who are treated for ALL. Patients are usually advised to discuss their options with their doctor. Based on their overall health and their goals and preferences, they may decide to undergo treatment for ALL. Some people may choose to forego treatment for the cancer, instead focusing on treatments that improve their symptoms and help them make the most of the time they have remaining.

Complications

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  • Bleeding
  • Damage to different organs from chemotherapy
  • Disseminated intravascular coagulation (DIC)
  • Relapse of ALL
  • Severe infection
  • Spread of the cancer to other parts of the body

Prognosis

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Children usually have a better outcome than adults. Almost all children go into complete remission. Without treatment, a person with ALL can expect to live for only about 3 months.

The following patients tend to do better:

  • Younger adults (especially those younger than age 50)
  • Children between the ages of 1 and 9
  • Those who have a WBC count below 50,000 when first diagnosed
  • Those who do not have a Philadelphia chromosome-positive ALL (a specific genetic change)
  • Those who achieve complete remission (disappearance of signs and symptoms of cancer) within 4 – 5 weeks of starting treatment.

Patients whose leukemia spreads to the brain or spinal cord tend to have a worse outcome.

References

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1. Harrison’s Principles of Internal Medicine, 16th Edition, Chapter 97. Malignancies of Lymphoid Cells. Clinical Features, Treatment, and Prognosis of Specific Lymphoid Malignancies.

2. “Acute lymphocytic leukemia (ALL), MedlinePlus”

3. “Acute lymphoblastic leukemia, Wikipedia”

4. “Acute lymphocytic leukemia Symptoms, MayoClinic”

5. Collier, J.A.B (1991). Oxford Handbook of Clinical Specialties, Third Edition. Oxford. pp. 810. ISBN 0-19-262116-5.

6. Harrison’s Principles of Internal Medicine, 16th EditioN, Chapter 97. Malignancies of Lymphoid Cells. Clinical Features, Treatment, and Prognosis of Specific Lymphoid Malignancies.

7. “Acute Lymphoblastic Leukemia, eMedicine”

8. “Leukemia Facts & Statistics, Leukemia & Lymphoma Society”

9. “Acute lymphocytic leukemia (ALL), Healthline”

10. “Acute lymphocytic leukemia Treatment and Drugs, MayoClinic”

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