Leukemia

What is Leukemia?

Leukemia is a cancer that begins in the bone marrow’s stem cells. The bone marrow is located within the bones’ cavities and is where blood cells are produced. It contains the cells that give rise to white blood cells (leukocytes), red blood cells (erythrocytes), and platelets.

It is a disease that affects white blood cells and is characterized by the accumulation of diseased cells in the bone marrow, which replace healthy blood cells, decreasing their normal number. 

In leukemia, an immature blood cell undergoes a genetic mutation that transforms it into a cancer cell. Abnormal, this cell multiplies faster and dies less than healthy cells, gradually replacing the normal cells of the bone marrow with abnormal cancerous cells.

In Brazil, leukemia is the ninth most common type of cancer among men and does not appear among the top ten types of cancer in women. For 2020, the INCA (National Cancer Institute) estimated 10,810 new cases of leukemia.

According to the World Health Organization (WHO), there were 474,519 new cases of leukemia worldwide in 2020, and the disease ranks 13th among the most common types of cancer in both males and females.

Among the factors that increase the risk of developing leukemia are smoking, exposure to benzene (a substance found in gasoline and widely used in the chemical industry), ionizing radiation (X-rays and gamma rays) from medical procedures (radiation therapy), certain chemotherapy drugs, formaldehyde, and pesticides. Being a carrier of Down syndrome, myelodysplastic syndrome, and other blood disorders also increases the risk of developing the disease.

Leukemia is a cancer that develops in the bone marrow’s stem cells, which are located within the bones’ cavities and where white blood cells, red blood cells, and platelets are produced. Cases of leukemia that cannot be prevented.

Types of leukemia

Leukemia is classified according to two criteria. One is the speed of its progression, which can be acute (progresses rapidly and produces cells that are not mature and cannot perform their functions) or chronic (progresses slowly and maintains a larger number of mature cells that can perform some of the normal functions).

The other is the type of blood cell/white blood cell that is diseased: myeloid or lymphoid.

There are subtypes defined by biological and genetic analyses. Combining the classification criteria, the four most common types are:

• Chronic lymphocytic leukemia (CLL): affects lymphoid cells and develops slowly. Most people with CLL are over 55 years old, and it rarely affects children. It is an acquired, not hereditary, disease;
• Chronic myeloid leukemia (CML): affects myeloid cells and develops slowly at first. It mainly affects adults. It can cause anemia, fatigue, infections, bleeding, and other side effects, but some patients are completely asymptomatic;
• Acute lymphoblastic leukemia (ALL): affects lymphoid cells and worsens rapidly. It is the most common type in young children but also occurs in adults;
• Acute myeloid leukemia (AML): affects myeloid cells and progresses rapidly. It occurs in both adults and children, but the incidence increases as a person ages.

Symptoms of leukemia

The main symptoms of leukemia result from the accumulation of defective cells in the bone marrow, which impairs or prevents the production of normal blood cells.

The decrease in red blood cells causes anemia, which is characterized by:

• Fatigue;
• Shortness of breath;
• Palpitations;
• Headache.

The reduction in white blood cells, in turn, lowers immunity, making the body more susceptible to recurring and potentially serious infections. 

Meanwhile, the decrease in platelets results in:

• Bleeding – most commonly from the gums and nose;
• Bruises on the skin – called ecchymosis; and
• Purple spots on the skin – known as petechiae

In general, the patient may also present with general symptoms of leukemia:

• Swollen lymph nodes, but not painful (mainly in the neck and armpits);
• Fever or night sweats;
• Unexplained weight loss;
• Abdominal discomfort (caused by swelling of the spleen or liver); and
• Bone and joint pain

If leukemia reaches the central nervous system, symptoms such as headaches, nausea, vomiting, double vision, and disorientation may occur.

Diagnosis of leukemia

In the presence of symptoms and suspicion of leukemia, specific medical evaluations should be conducted, including blood tests. The main test is a complete blood count (CBC), which, if positive, will show alterations in white blood cells – often an increase in their number, and very rarely a decrease – associated or not with a decrease in red blood cells and platelets.

Other laboratory tests to be performed include:

• Coagulation studies (PT, PTT, fibrinogen);
• Biochemical analyses (renal function, hepatic function, electrolytes);
• Blood cultures (if fever is present);
• Urine or other biological fluid cultures (if infection is suspected);
• Chest and abdominal imaging (for respiratory and gastrointestinal symptoms).

Confirmation of the diagnosis is done with a bone marrow aspiration and biopsy. A small amount of blood and bone marrow is taken from the spongy tissue inside the bone for cytological (evaluation of cell shape), cytogenetic (evaluation of chromosomes), molecular (evaluation of genetic mutations), and immunophenotypic (evaluation of cell phenotype) analysis.

In addition to that, other tests used for a definitive diagnosis include:

• Hematoscopy – confirms the presence of circulating blasts in peripheral blood;
• Immunophenotyping of peripheral blood – confirms the percentage and phenotype of blasts, allowing characterization of the leukemia subtype;
• FISH (fluorescence in situ hybridization) for certain cytogenetic alterations – allows for the detection of specific alterations that determine the choice of initial therapy; and
• PCR (polymerase chain reaction) for recurrent genetic alterations – essential for classification according to the WHO and for guiding prognosis and treatment choice.

In some cases, a bone marrow biopsy may be necessary, performed by a pathologist analyzing a small piece of bone from the hip.

Treatment for leukemia

Treatment for leukemia aims to destroy the diseased cells so that the bone marrow can resume normal cell production.

In cases of acute leukemia, treatment involves chemotherapy, control of infectious and hemorrhagic complications, and prevention or treatment of disease in the central nervous system (brain and spinal cord). In some cases, a bone marrow transplant may be indicated.

The first step is to achieve complete remission, meaning a return to a state of apparent normality after chemotherapy with a combination of drugs. This outcome can be achieved around one month after the start of treatment (induction phase of remission), when blood and bone marrow tests no longer show abnormal cells.

However, research shows that many leukemic cells remain in the body – residual disease – so it is necessary to continue treatment to prevent relapse. In subsequent stages, treatment varies according to the type of cell affected by leukemia. In lymphoid cells, this can last more than two years, and in myeloid cells, less than one year (except in cases of acute promyelocytic leukemia, which also lasts more than 2 years).

In acute lymphoblastic leukemia (ALL), treatment has three phases: induction of remission, consolidation (intensive treatment with chemotherapy not used previously), and maintenance (treatment is gentler and continuous for several months). Throughout the process, hospitalization may be necessary due to infection resulting from the decrease in normal white blood cells and other complications of treatment.

In acute myeloid leukemia (AML), maintenance therapy is only necessary for cases of acute promyelocytic leukemia (a special subtype of AML related to severe bleeding at diagnosis). In these cases, there is a specific genetic mutation that can be detected in bone marrow tests, and treatment with a combination of chemotherapy and oral medication (all-trans retinoic acid) allows for very high cure rates.

The treatment of chronic myeloid leukemia (CML) targets a specific pathway (inhibiting the multiplication of cancer cells without affecting healthy cells). This leukemia results from the emergence of a specific gene (BCR-ABL gene) capable of increasing cell multiplication through the protein called tyrosine kinase. An oral medication from the class of protein inhibitors is used. If the disease shows resistance after this stage, other second or third generation tyrosine kinase inhibitors are available, and in rare cases, the patient may be referred for a bone marrow transplant.

In chronic lymphocytic leukemia (CLL), a large proportion of patients will not need to be treated immediately, or may never need treatment at all.

Treatment should only be initiated in cases of rapidly growing disease following a specific protocol. Treatment may include oral medications such as Bruton’s tyrosine kinase inhibitors or BCL2 inhibitors. Currently, these medications provide excellent disease control. The choice will depend on clinical aspects of the patient, such as age, presence of other diseases, choice between continuous or time-limited treatment, and the characteristics of the disease itself.

Prevention for Leukemia

Most cases of leukemia do not have modifiable risk factors, meaning that cases of leukemia, such as leukemia in children, cannot be prevented.

Avoiding exposure to substances such as benzene, formaldehyde, and pesticides, however, can reduce the risk of developing leukemia. The same applies to smoking, a risk factor for acute myeloid leukemia: quitting smoking is always a good idea and can, as a bonus, prevent other types of cancer (especially lung, mouth, and bladder cancer), as well as diseases such as emphysema, heart attack, and stroke.