Leukemia

Leukemia is a cancer that starts in stem cells in the bone marrow. Bone marrow is in the cavity of the bones and is where blood cells are produced. It contains the cells that give rise to white blood cells (leukocytes), red blood cells (red blood cells or erythrocytes) and platelets.

It is a disease that affects white blood cells and whose main characteristic is the accumulation of diseased cells in the bone marrow – they replace healthy blood cells, decreasing their normal number.

In leukemia, a blood cell that is not yet mature undergoes a genetic mutation that turns it into a cancer cell. Abnormally, this cell multiplies faster and dies less than healthy cells, and this is how normal bone marrow cells are replaced by abnormal cancerous cells.

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

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

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), to ionizing radiation (X and gamma rays) from medical procedures (radiotherapy), some chemotherapy drugs, formaldehyde and pesticides. Having Down syndrome, myelodysplastic syndrome and other blood disorders also increases the risk of developing the disease.

Types of leukemia

Leukemia is classified according to two criteria. One of them is the speed of its progression, which can be acute (progresses quickly and produces cells that are not mature and cannot perform their functions) or chronic (progresses slowly and maintains a greater number of mature cells that are able to 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 analysis. Combining the classification criteria, there are four most common types:

• Chronic lymphoid leukemia (CLL): affects lymphoid cells and develops slowly. Most people with CLL are over age 55, and it rarely affects children. It is an acquired disease, not hereditary;
• 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 problems, but some patients are completely asymptomatic;
• Acute lymphoid leukemia (ALL): affects lymphoid cells and gets worse quickly. It is the most common type in young children, but it 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.

Leukemia symptoms

The main symptoms of leukemia are a consequence of the accumulation of defective cells in the bone marrow that impairs or prevents the production of normal blood cells.

A decrease in red blood cells causes anemia, the signs of which are:

• Fatigue;
• Shortness of breath;
• Palpitation;
• Headache

The reduction of white blood cells, in turn, causes a drop in immunity, which leaves the body more susceptible to recurrent infections that can be serious.

A decrease in platelets causes:

• Bleeding – the most common being from the gums and nose;
• Purple spots on the skin – called ecchymoses; and
• Purple spots on the skin – known as petechiae

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

• Swollen but painless lymph nodes (especially in the neck and armpit area)
• Fever or night sweats;
• Weight loss for no apparent reason;
• Abdominal discomfort (caused by swelling of the spleen or liver) and
• Bone and joint pain

If leukemia reaches the central nervous system, headaches, nausea, vomiting, double vision and disorientation can result.

Leukemia diagnosis

In the face of symptoms and suspicion of leukemia, blood tests should be performed for specific medical evaluation. The main one of these tests is the complete blood count, which, if positive, will show changes in leukocytes – with an increase in their number in most cases, and very rarely a decrease – associated or not with a decrease in red blood cells and platelets.

Other laboratory analyzes to be performed are:

• Coagulation study (TAP, PTT, fibrinogen);
• Biochemical analysis (kidney, liver, electrolytes);
• Blood cultures (in the presence of fever);
• Culture of urine or other biological fluids (if associated infections are suspected);
• Chest and abdomen imaging exams (in the face of respiratory and gastrointestinal symptoms).

Confirmation of the diagnosis is made with the myelogram, which is the examination of the bone marrow. A small amount of blood is taken from the spongy material inside the bone for cytological (assessment of cell shape), cytogenetic (assessment of chromosomes), molecular (assessment of genetic mutations) and immunophenotypic (assessment of cell phenotype) analysis.

In addition to it, the following tests are used for the diagnosis of certainty:

• Hematoscopy – confirms the presence of circulating blasts in peripheral blood;
• Peripheral blood immunophenotyping – confirms the percentage and phenotype of blasts, which allows characterizing the leukemia subtype;
• FISH (fluorescence in situ hybridization) for certain cytogenetic alterations – allows searching for 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 prognostic guidance and treatment choice.

In some cases, it may be necessary to perform a bone marrow biopsy, performed with the analysis of a small piece of the hip bone by a pathologist.

Treatment

Leukemia treatment aims to destroy diseased cells so that the bone marrow can produce normal cells again.

In cases of acute leukemias, treatment involves chemotherapy, control of infectious and hemorrhagic complications, and prevention or control of the disease in the central nervous system (brain and spinal cord). In some cases, bone marrow transplantation is indicated.

The first step is aimed at achieving complete remission, that is, returning to a state of apparent normality after chemotherapy with the combination of drugs. This result can be achieved around a month after starting treatment (remission induction phase), when blood and bone marrow tests no longer show abnormal cells.

However, as research shows that many leukemic cells remain in the body – the residual disease -, it is necessary to continue the treatment so that there is no relapse. In the following steps, treatment varies according to the type of cell affected by the leukemia. In lymph nodes, this can last more than two years, and in myeloids, less than a 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 drugs not previously used), and maintenance (treatment is milder and continuous for several months). During the entire process, hospitalization may be necessary due to infection resulting from the fall in normal white blood cells and other complications of the treatment itself.

In acute myeloid leukemia (AML), the maintenance step is only necessary for cases of acute promyelocytic leukemia (a special subtype of AML related to major 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 an oral pill (tretinoin) provides very high cure rates.

The treatment of chronic myeloid leukemia (CML) is targeted (inhibits 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 a protein called tyrosine kinase. An oral drug from the protein inhibitor class is used. If there is resistance to the disease after this stage, chemotherapy or bone marrow transplantation is initiated.

In chronic lymphocytic leukemia (CLL), treatment may include chemotherapeutic, immunological (monoclonal antibodies) and oral agents. The choice will depend on the patient’s clinical aspects, such as age, presence of other diseases, ability to tolerate chemotherapy and the characteristics of the disease itself.

Prevention

Most cases of leukemia do not have risk factors that can be modified, that is, they are cases of leukemia that cannot be prevented.

Avoiding exposure to substances such as benzene, formaldehyde and pesticides, however, is a way to reduce the risk of developing leukemia. The same goes for 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) as well as diseases like emphysema , myocardial infarction and stroke.