Prognostic Factors For Children With Acute Lymphoid Leukemia (ALL)

Prognostic Factors For Children With Acute Lymphoid Leukemia (ALL)
Acute lymphoblastic leukemia, also known as acute lymphocytic leukemia or acute lymphoid leukemia (ALL), is an acute form of leukemia, or cancer of the white blood cells, characterized by the overproduction and accumulation of cancerous, immature white blood cells, known as lymphoblasts. In persons with ALL, lymphoblasts are overproduced in the bone marrow and continuously multiply, causing damage and death by inhibiting the production of normal cells (such as red and white blood cells and platelets) in the bone marrow and by spreading (infiltrating) 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 symptoms of ALL are indicative of a reduced production of functional blood cells, because leukemia wastes the resources of the bone marrow that are normally used to produce new, functioning blood cells. These symptoms can include fever, increased risk of infection (especially bacterial infections like pneumonia, due to neutropenia; symptoms of such an infection include shortness of breath, chest pain, cough, vomiting, changes in bowel or bladder habits), increased tendency to bleed (due to thrombocytopenia), and signs indicative of anemia, including pallor, tachycardia (high heart rate), fatigue, and headache. 

About 6,000 cases are reported in the United States every year. Internationally, ALL is more common in Caucasians than in Africans; it is more common in Hispanics and in Latin America. Cure is a realistic goal and is achieved in more than 80% of affected children, although only 20-40% of adults are cured. "Acute" is defined by the World Health organization standards, in which greater than 20% of the cells in the bone marrow are blasts. Chronic lymphocytic leukemia is defined as having less than 20% blasts in the bone marrow.

ALL was one of the first cancers for which an effective chemotherapeutic treatment was developed. Antifolates like aminopterin and methotrexate were developed in the late 1940s by Sidney Farber and Yellapragada Subbarow.[5][6] At that time, a doctor did not need a patient's or parent's consent to try an experimental treatment as the Nuremberg code had not yet been signed. Desperate to save his patients, Farber initially tried folic acid supplementation as a treatment for ALL. This had disastrous consequences and he likely accelerated the children's deaths.

SYMPTOMS OF ACUTE LYMPHOID LEUKEMIA

Acute lymphoblastic leukemia usually starts slowly before rapidly becoming severe as the number of immature white blood cells in your blood increases.

Most of the symptoms are caused by the lack of healthy blood cells in your blood supply. Symptoms include:
  • pale skin
  • feeling tired and breathless
  • repeated infections over a short space of time
  • unusual and frequent bleeding, such as bleeding gums or nosebleeds
  • high temperature (fever) of 38C (100.4F) or above
  • night sweats
  • bone and joint pain
  • easily bruised skin
  • swollen lymph nodes (glands)
  • abdominal pain – caused by a swollen liver or spleen
  • unexplained weight loss 
  • a purple skin rash (purpura)

In some cases, the affected cells can spread from your bloodstream into your central nervous system. This can cause a series of neurological symptoms (related to the brain and nervous system), including:
  • headaches 
  • seizures (fits)
  • vomiting
  • blurred vision
  • dizziness

PROGNOSTIC FACTORS FOR CHILDREN 
WITH ACUTE LYMPHOID LEUKEMIA (ALL)

Acute Lymphoid Leukemia (ALL)  

Children with ALL are often divided into risk groups (such as standard-risk, high-risk, or very high-risk), with more intensive treatment given to higher risk patients. Generally, children at low risk have a better outlook than those at very high risk.

While all of the following are prognostic factors, only certain ones are used to determine which risk group a child falls into. (The first 2 factors – age at diagnosis and initial white blood cell count – are thought to be the most important.) It’s important to know that even children with some poor prognostic factors can often still be cured.

1. Age at diagnosis
Children between the ages of 1 and 9 with B-cell ALL tend to have better cure rates. Children younger than 1 year and children 10 years or older are considered high-risk patients. The outlook in T-cell ALL isn’t affected much by age.

2. Subtype of ALL
Children with pre-B, common, or early pre-B-cell ALL generally do better than those with mature B-cell (Burkitt) leukemia. The outlook for T-cell ALL seems to be about the same as that for B-cell ALL as long as treatment is intense enough.

3. Gender
Girls with ALL may have a slightly higher chance of being cured than boys. As treatments have improved in recent years, this difference has shrunk.

4. Race/ethnicity
African-American and Hispanic children with ALL tend to have a lower cure rate than children of other races.

5. Spread to certain organs
Spread of the leukemia into the cerebrospinal fluid (the fluid around the brain and spinal cord), or to the testicles in boys, lowers the chance of being cured. Enlargement of the spleen and liver is usually linked to a high WBC count, but some doctors view this as a separate sign that the outlook is not as favorable.

6. Number of chromosomes
Patients are more likely to be cured if their leukemia cells have more than 50 chromosomes (called hyperdiploidy), especially if there is an extra chromosome 4, 10, or 17. Hyperdiploidy can also be expressed as a  DNA index of more than 1.16. Children whose leukemia cells have fewer chromosomes than the normal 46 (known as hypodiploidy) have a less favorable outlook.

7. Chromosome translocations
Translocations occur when chromosomes swap some of their genetic material (DNA). Children whose leukemia cells have a translocation between chromosomes 12 and 21 are more likely to be cured. Those with a translocation between chromosomes 9 and 22 (the Philadelphia chromosome), 1 and 19, or 4 and 11 tend to have a less favorable prognosis. Some of these “poor” prognostic factors have become less important in recent years as treatment has improved.

8. Response to treatment
Children whose leukemia responds completely (major reduction of cancer cells in the bone marrow) within 1 to 2 weeks of chemotherapy have a better outlook than those whose leukemia does not. Children whose cancer does not respond as well may be given more intensive chemotherapy.

References:

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