Acute Leukemias

Acute Leukemias

Blood is a fluid in our body that carries nutrients, oxygen and hormones to cells, regulates the blood clotting system, performs immunological functions, and plays a critical role in regulating body temperature. Although it varies with age in children, an average of 80 ml/kg of blood is present. An average adult has 4–5 liters of blood, and apart from the fluid called plasma (55%), the remainder consists of 3 types of cells.

Erythrocytes (red blood cells) are the cells that carry oxygen to tissues. Leukocytes (white blood cells) play a role in the body's defense system. Platelets (blood platelets) are the cells that form a plug when bleeding occurs, stopping the bleeding. More than 500 billion cells are produced in the bone marrow each day. Around 100 billion neutrophils are produced per day; they live for a few hours in the blood and a few days in tissues. Monocytes clear dead cells from tissues and take part in tissue regeneration.

Among childhood cancers, the most common are leukemias, central nervous system (brain and spinal cord) tumors, and lymphomas. Leukemias are cancers that manifest as uncontrolled and excessive proliferation of leukocytes (white blood cells) produced in the bone marrow. In the United States, the incidence of ALL (acute lymphoblastic leukemia) is 34 cases per 100,000 children, and 2,500–3,000 children are diagnosed each year. It is most common between the ages of 2 and 5. It accounts for 25–30% of all childhood cancers .

In our country, according to the 2009–2018 data of TPOG (Turkish Pediatric Oncology Group) and TPHD (Turkish Pediatric Hematology Association), the most common childhood cancers in our country are leukemias, at a rate of 27.9%.

97% of all childhood leukemias are acute leukemias:

1- Acute lymphoblastic leukemia (ALL) – 80%:

85% of ALL is B-cell acute lymphoblastic leukemia (B-ALL)

15% of ALL is T-cell acute lymphoblastic leukemia (T-ALL)

2- Acute myeloblastic leukemia (AML) – 15%

3- Chronic myeloid leukemias constitute 3% of all childhood leukemias.

Etiology (Causes of Leukemia)

The etiology (cause) of acute leukemia has not been fully elucidated. It may arise from the occurrence of a series of genetic events (e.g., structural changes in DNA, DNA lesions, copy number changes and mutations). The vast majority of these are of somatic origin. That is, they are not transmitted through parents; they are genetic mutations that occur in the body of the affected person. In many cases, these genetic events can be traced back to cord blood, indicating the prenatal origin of childhood leukemia. Some of these somatic genetic events can also be detected in newborns who never develop leukemia. Most cases of leukemia result from somatic genetic changes rather than hereditary genetic predisposition; therefore, the risk of leukemia in siblings is low. However, if leukemia develops in one of identical twins within the first 5 years of life, the risk of leukemia in the other twin is 20%. In some genetic diseases the risk is also higher than the population frequency (Down syndrome, Fanconi aplastic anemia, Bloom syndrome, etc.).

Not only genetic causes alone, but also environmental factors can play a role in the development of leukemia. The following environmental factors play a role in the formation of leukemia:

1- Ionizing radiation

2- Chemicals (such as benzene in acute myeloid leukemia)

3- Medications (for example, the use of alkylating agents alone or together with radiation therapy increases the risk of AML)

Epidemiological evidence shows that exposure to pesticides (agricultural chemicals), especially during pregnancy, increases the risk of childhood leukemia, particularly among infants. A very recent Japanese study analyzed a large data pool including 104,062 infants. It was shown that when mothers were exposed to cancer drugs during pregnancy, the risk of leukemia in children increased after age 1. It was reported that maternal exposure during pregnancy to paints, solvents and petroleum products from household and occupational sources increased the risk of childhood acute lymphoblastic leukemia by 1.2 to 1.4 times.

Recent comprehensive reviews have reported a statistically significant increase in the risk of childhood leukemia associated with various air pollution markers (e.g., benzene, nitrogen dioxide from fossil fuels, and proximity to traffic density).

Clinical signs:

Leukemia cells are characterized by a pause in the developmental process of normal cells and abnormal proliferation at this stage. Therefore, these abnormal cells begin to completely cover the bone marrow, and the production of normal cells becomes insufficient. Because the bone marrow cannot produce enough of the red blood cells that carry oxygen in the blood (erythrocytes), the white blood cells of the immune system (leukocytes), and the platelets that play a role in the clotting system (thrombocytes), the following symptoms appear:

Anemia resulting from a deficiency of red blood cells (erythrocytes):

Paleness,

Weakness, fatigue, exhaustion,

Palpitations,

Loss of appetite

Due to a deficiency of white blood cells (leukocytes):

Fever

Infections

Mouth sores

Due to a deficiency of platelets (thrombocytes):

Easy bruising (bruising below the knees is generally considered normal in children. What is meant here is bruising in unexpected areas),

Gum bleeding,

Nosebleeds (especially bilateral),

Non-blanching red spots on the skin (petechiae, purpura),

Less commonly, internal bleeding (e.g., intracranial bleeding) may occur.

The most common symptoms and most frequent physical examination findings:

Enlarged liver 68%

Enlarged spleen 63%

Fever 60%

Weakness, fatigue, exhaustion 50%

Abnormal enlargement of lymph nodes 50%

Bleeding signs (petechiae, purpura) 48%

Pallor 40%

Joint pain 23%

Rare symptoms

In 5% of patients, due to involvement of the central nervous system (brain, spinal cord): headache, vomiting, loss of balance when walking, urinary and fecal incontinence

In 1% of patients, due to involvement of the genitourinary system: painless testicular enlargement, blood in the urine

Shortness of breath due to masses associated with involvement of the mediastinum (chest cavity)

Very rarely, skin lesions and heart failure due to severe anemia may occur.

How Is It Diagnosed?

A complete blood count (CBC) is performed to determine how many blood cells of each type are present in the blood. It is an indispensable test in the diagnosis of leukemia. However, it is not sufficient on its own. A peripheral blood smear, a special test performed on a single drop of blood, is spread on a glass slide and examined under a microscope. An abnormal number of blood cells and changes in the appearance of these cells may lead the physician to suspect leukemia.

In most children with leukemia, abnormalities are found in the number of red blood cells, white blood cells and platelets. Most of the red blood cells in the blood will be blasts (leukemia cells), an early type of blood cell normally found only in the bone marrow. Although these findings may lead a physician to suspect leukemia in the child, the disease usually cannot be definitively diagnosed without examining a sample of bone marrow cells. The bone marrow sample is usually taken from the hip bone (pelvis) under anesthesia using a special needle. It is examined under a microscope by a hematology specialist. At the same time, a definitive diagnosis is made through detailed examination of the cells called flow cytometry.

TREATMENT

Treatment for acute lymphoblastic leukemia normally lasts two years. The first six months are mostly spent in hospital receiving intravenous treatment, and the remaining 1.5 years are spent with outpatient oral medications. Today, the worldwide response rate to treatment has reached the 80–90% range. However, a desired response to treatment may not always be achieved. In cases of treatment resistance and relapse (recurrence of the disease), high-dose chemotherapy and bone marrow transplantation may come into play.

In recent years, new therapies such as CAR (Chimeric antigen receptor) T cell therapy, in which the body's own fighting T lymphocytes are sensitized to leukemia cells in the laboratory so that they target leukemia cells, are also promising.

PREVENTION

A combined analysis of original data from 12 studies conducted worldwide has shown that taking prenatal folic acid and vitamin B12 before becoming pregnant and during pregnancy reduces the risk of childhood acute leukemia. Similarly, the current literature generally indicates that a healthy maternal diet during conception/early pregnancy, and the child's diet in the first years of life, are protective. While decreased leukemia risks have been associated with consumption of fruit, legumes, proteins, soybeans and milk/dairy products, increased risks have been associated with consumption of added fats and dried/smoked meat or fish.

It is well documented that breastfeeding generally reduces the risk of childhood leukemia by ∼10%, and by 20% for infants breastfed for 6 months or longer.

Currently, there are no cancer prevention measures we are aware of for the primary prevention of childhood cancer. Until additional information strongly refutes our current knowledge, more serious and comprehensive measures should be taken to avoid chemical exposures from the various sources mentioned above for parents who are expecting a child, mothers who have given birth, and young children.