What is leukemia?

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Overview

Leukemia is a disease characterized by the cancerous, abnormal, uncontrolled proliferation of leukocytes (white blood cells), which play an important role in the formation of the immune system. These cancerous cells crowd the bone marrow, which contains cells that produce blood cells, so there is less room for healthy blood cells.

Acquired mutations in hematopoietic cells, which produce blood cells in the bone marrow, play a role in the development of the disease. Often there is no trigger for this mutation and the disease is coincidental. In most patients, this genetic change develops at the stem cell level and is acquired. In very rare cases of leukemia, familial predisposition is observed.

Although rare, factors such as exposure to high amounts of radiation, a history of previous chemotherapy, or chromosomal diseases such as Down syndrome may increase the risk of leukemia.

What are the signs and symptoms of leukemia?

The signs and symptoms of leukemia are often due to the bone marrow’s decreased ability to produce enough healthy blood cells.

The decrease in erythrocytes, the red blood cells responsible for distributing oxygen throughout the body, causes anemia, resulting in symptoms such as easy exhaustion, weakness, fatigue, dizziness and palpitations. Especially in the elderly, symptoms of cardiovascular disease such as angina may be added to other complaints. In general terms, the more severe the anemia, the greater the health impact on patients.

The decrease in healthy white blood cells, which are responsible for the body’s defense against infections, causes a marked increase in the susceptibility to infections. Affected patients often present with fever. Sometimes complaints related to organ systems affected by infection may also be observed. Examples of these complaints include cough, sputum, sore throat, diarrhea, painful urination. Although difficult to distinguish, in some cases fever may be due to the disease itself rather than an infection.

Another important blood cell produced by the bone marrow are platelets, which are involved in blood clotting. Decreased production of these cells, small hemorrhages called petechiae or larger bruises may appear on the skin. Apart from the skin, bleeding from mucous membranes such as the mouth, gums, nose, urine and rectal area can also be observed.

Other symptoms may include weight loss as the disease causes loss of appetite and the rapidly proliferating cells use high amounts of energy. Some cases may present with prominent widespread bone pain due to leukemia cells overcrowding the bone marrow. Leukemia cells may crowd organs other than the bone marrow as well. These organs are often the liver, spleen and lymph nodes, but it is possible to see disease involvement in all organs, in which case patients may develop lymph node swelling in the neck, armpits and groin. In cases presenting with liver and/or spleen enlargement, complaints such as early satiety, abdominal swelling and abdominal pain are observed. Some types of leukemia may present with involvement of the gums, causing excessive swelling of the gums.

What are the types of leukemia?

Each type of leukemia has different characteristics. Some leukemias may require immediate treatment, while others may be monitored for years without treatment.

White blood cells belong to the lymphoid or myeloid lineage. In leukemia typing, the white blood cell lineage from which the leukemia originates is first evaluated. Leukemia is also classified as acute or chronic depending on the clinical course of the disease.

Acute leukemias have a more rapid course; symptoms are usually of recent onset and quite prominent. If treatment of acute leukemia is not started quickly, patients die within days or weeks, often from complications related to bone marrow failure.

The most common acute leukemia in adulthood is acute myeloid leukemia, while in childhood it is acute lymphoblastic leukemia, which is often of lymphoid origin. Although both are mainly treated with chemotherapy, they differ in treatment modalities.

In chronic leukemia, the symptoms may be milder. About half of the patients have no obvious complaints and may be diagnosed with leukemia as a result of examinations performed for other reasons. Some chronic leukemias can be monitored without treatment, while some patients need treatment according to the stage and subtype of chronic leukemia. Chronic leukemias have a longer life expectancy than acute leukemias.

An example of chronic leukemia of lymphoid origin is chronic lymphocytic leukemia, the most prevalent type of leukemia in Western societies. The likelihood of developing this disease increases with age. But although it is usually a disease of advanced age, it can also be seen in young people. While this type of leukemia is monitored without treatment in some cases, the disease progresses to an advanced stage as the leukemic tumor burden increases, requiring treatment. An example of chronic leukemia of myeloid origin is chronic myeloid leukemia, which occurs in younger people, on average around age 50. This type of leukemia is now successfully treated with a tyrosine kinase inhibitor such as imatinib, a targeted agent.

How is leukemia treated?

Treatment methods and options in leukemia vary according to the subtype of leukemia. Treatment is planned according to the cell type from which the leukemia originates and whether the leukemia is acute or chronic. Treatment plans can vary widely. While some chronic leukemias can be monitored without treatment, in some leukemias, usually acute leukemias, aggressive treatments such as chemotherapy need to be started quickly. The drugs used in treatment can be administered orally, subcutaneously or intravenously depending on their chemical characteristic. Treatment options are evaluated based on criteria such as the patient’s age, performance status, comorbidities (heart, kidney, etc.) and genetic characteristics of leukemic cells.

Treatment options for leukemia can be summarized as follows:

• Chemotherapy: Cancer cells multiply rapidly and uncontrollably. Chemotherapeutic drugs prevent these cells from multiplying through various mechanisms, usually by disrupting the cells’ DNA production. In leukemia treatment, multiple chemotherapy drugs with different mechanisms are often used in combination. This not only increases their effectiveness but also helps prevent the cancer cells from developing resistance to chemotherapy drugs.

• Targeted therapies: Proteins caused by certain mutations in cancer cells or proteins that they naturally carry on their surface can be targets for drugs. Since targeted drugs are more specific to diseased cells, they usually have a lower potential for side effects. They can be used alone or in combination with other drugs.

• Immunotherapies: This type of treatment aims to kill leukemic cells by directing the patient’s immune system towards them.

• Allogeneic Hematopoietic Stem Cell (Bone Marrow) Transplantation: Patients with acute leukemia may need transplantation of hematopoietic (blood cell producing) stem cells from a healthy donor with fully compatible tissue groups (HLA) in order to minimize the risk of relapse after the leukemia has been brought under control. As the probability of a full-match is highest in siblings, siblings suitable in terms of age and health are tested first. If there is no matching sibling available, an application is made to the Turkish Stem Cell Coordination Center where the tissue groups of volunteer donors are registered, and if no match can be found, foreign stem cell banks are searched for a suitable donor. In patients for whom no compatible donor can be found despite all efforts, allogeneic stem cell transplantation from an HLA half-match can be an option. Allogeneic stem cell transplantation is not required in acute leukemias patients who are considered “good risk” according to the genetic characteristics of leukemic cells.

• Autologous Hematopoietic Stem Cell Transplantation: Patients with acute myeloid leukemia, especially those in the good-risk group, can undergo autologous stem cell transplantation to reduce the risk of relapse. This type of transplantation involves collecting the patient’s own (autologous) stem cells once the disease has been brought under control and the crowding of the bone marrow by leukemic cells has been cleared out (complete remission).