Leukemia
Leukemia is a group of blood cancers that usually begin in the bone marrow and produce high numbers of abnormal blood cells. These blood cells are not fully developed and are called blasts or leukemia cells. Symptoms may include bleeding and bruising, bone pain, fatigue, fever, and an increased risk of infections. These symptoms occur due to a lack of normal blood cells. Diagnosis is typically made by blood tests or bone marrow biopsy.
The exact cause of leukemia is unknown. A combination of genetic factors and environmental factors are believed to play a role. Risk factors include smoking, ionizing radiation, petrochemicals, prior chemotherapy, and Down syndrome. People with a family history of leukemia are also at higher risk. There are four main types of leukemia—acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia and chronic myeloid leukemia —and a number of less common types. Leukemias and lymphomas both belong to a broader group of tumors that affect the blood, bone marrow, and lymphoid system, known as tumors of the hematopoietic and lymphoid tissues.
Treatment may involve some combination of chemotherapy, radiation therapy, targeted therapy, and bone marrow transplant, with supportive and palliative care provided as needed. Certain types of leukemia may be managed with watchful waiting. The success of treatment depends on the type of leukemia and the age of the person. Outcomes have improved in the developed world. Five-year survival rate was 68% in the United States in the period from 2015 to 2021. In children under 15 in first-world countries, the five-year survival rate is greater than 60% or even 90%, depending on the type of leukemia. For infants, the survival rate is around 40%. In children who are cancer-free five years after diagnosis of acute leukemia, the cancer is unlikely to return.
In 2015, leukemia was present in 2.3 million people worldwide and caused 353,500 deaths. In 2012, it had newly developed in 352,000 people. It is the most common type of cancer in children, with three-quarters of leukemia cases in children being the acute lymphoblastic type. However, over 90% of all leukemias are diagnosed in adults, CLL and AML being most common. It occurs more commonly in the developed world.
Classification
General classification
Clinically and pathologically, leukemia is subdivided into a variety of large groups. The first division is between its acute and chronic forms:- Acute leukemia is characterized by a rapid increase in the number of immature blood cells. The crowding that results from such cells makes the bone marrow unable to produce healthy blood cells resulting in low hemoglobin and low platelets. Immediate treatment is required in acute leukemia because of the rapid progression and accumulation of the malignant cells, which then spill over into the bloodstream and spread to other organs of the body. Acute forms of leukemia are the most common forms of leukemia in children.
- Chronic leukemia is characterized by the excessive buildup of relatively mature, but still abnormal, white blood cells. Typically taking months or years to progress, the cells are produced at a much higher rate than normal, resulting in many abnormal white blood cells. Whereas acute leukemia must be treated immediately, chronic forms are sometimes monitored for some time before treatment to ensure maximum effectiveness of therapy. Chronic leukemia mostly occurs in older people but can occur in any age group.
- In lymphoblastic or lymphocytic leukemias, the cancerous change takes place in a type of marrow cell that normally goes on to form lymphocytes, which are infection-fighting immune system cells. Most lymphocytic leukemias involve a specific subtype of lymphocyte, the B cell.
- In myeloid or myelogenous leukemias, the cancerous change takes place in a type of marrow cell that normally goes on to form red blood cells, some other types of white cells, and platelets.
Specific types
- Acute lymphoblastic leukemia is the most common type of leukemia in young children. It also affects adults, especially those 65 and older. Standard treatments involve chemotherapy and radiotherapy. Subtypes include precursor B acute lymphoblastic leukemia, precursor T acute lymphoblastic leukemia, Burkitt's leukemia, and acute biphenotypic leukemia. While most cases of ALL occur in children, 80% of deaths from ALL occur in adults.
- Chronic lymphocytic leukemia most often affects adults over the age of 55. It sometimes occurs in younger adults, but it almost never affects children. Two-thirds of affected people are men. The five-year survival rate is 85%. It is incurable, but there are many effective treatments. One subtype is B-cell prolymphocytic leukemia, a more aggressive disease.
- Acute myelogenous leukemia occurs far more commonly in adults than in children, and more commonly in men than women. It is treated with chemotherapy. The five-year survival rate is 20%. Subtypes of AML include acute promyelocytic leukemia, acute myeloblastic leukemia, and acute megakaryoblastic leukemia.
- Chronic myelogenous leukemia occurs mainly in adults; a very small number of children also develop this disease. It is treated with imatinib or other drugs. The five-year survival rate is 90%. One subtype is chronic myelomonocytic leukemia.
- Hairy cell leukemia is sometimes considered a subset of chronic lymphocytic leukemia, but does not fit neatly into this category. About 80% of affected people are adult men. No cases in children have been reported. HCL is incurable but easily treatable. Survival is 96% to 100% at ten years.
- T-cell prolymphocytic leukemia is a very rare and aggressive leukemia affecting adults; somewhat more men than women are diagnosed with this disease. Despite its overall rarity, it is the most common type of mature T cell leukemia; nearly all other leukemias involve B cells. It is difficult to treat, and the median survival is measured in months.
- Large granular lymphocytic leukemia may involve either T-cells or NK cells; like hairy cell leukemia, which involves solely B cells, it is a rare and indolent leukemia.
- Adult T-cell leukemia is caused by human T-lymphotropic virus, a virus similar to HIV. Like HIV, HTLV infects CD4+ T-cells and replicates within them; however, unlike HIV, it does not destroy them. Instead, HTLV "immortalizes" the infected T-cells, giving them the ability to proliferate abnormally. Human T-cell lymphotropic virus types I and II are endemic in certain areas of the world.
- Clonal eosinophilias are a group of blood disorders characterized by the growth of eosinophils in the bone marrow, blood, and/or other tissues. They may be pre-cancerous or cancerous. Clonal eosinophilias involve a "clone" of eosinophils, i.e., a group of genetically identical eosinophils that all grew from the same mutated ancestor cell. These disorders may evolve into chronic eosinophilic leukemia or may be associated with various forms of myeloid neoplasms, lymphoid neoplasms, myelofibrosis, or the myelodysplastic syndrome.
Pre-leukemia
- Transient myeloproliferative disease, also termed transient leukemia, involves the abnormal proliferation of a clone of non-cancerous megakaryoblasts. The disease is restricted to individuals with Down syndrome or genetic changes similar to those in Down syndrome, develops in a baby during pregnancy or shortly after birth, and resolves within 3 months or, in ~10% of cases, progresses to acute megakaryoblastic leukemia. Transient myeloid leukemia is a pre-leukemic condition.
- Clonal hematopoiesis is a common age-related phenomenon with a low risk of progression to myelodysplastic syndrome and leukemia. Once MDS has developed, the risk of progression to acute leukemia can be assessed using the International Prognostic Scoring System.
- Monoclonal B-cell lymphocytosis has a low risk of progression to B-cell leukemia.
Signs and symptoms
Damage to the bone marrow, by way of displacing the normal bone marrow cells with higher numbers of immature white blood cells, results in a lack of blood platelets, which are important in the blood clotting process. This means people with leukemia may easily become bruised, bleed excessively, or develop pinprick bleeds.
White blood cells, which are involved in fighting pathogens, may be suppressed or dysfunctional. This could cause the person's immune system to be unable to fight off a simple infection or to start attacking other body cells. Because leukemia prevents the immune system from working normally, some people experience frequent infection, ranging from infected tonsils, sores in the mouth, or diarrhea to life-threatening pneumonia or opportunistic infections.
Finally, the red blood cell deficiency leads to anemia, which may cause dyspnea and pallor.
Some people experience other symptoms, such as fevers, chills, night sweats, weakness in the limbs, feeling fatigued and other common flu-like symptoms. Some people experience nausea or a feeling of fullness due to an enlarged liver and spleen; this can result in unintentional weight loss. Blasts affected by the disease may come together and become swollen in the liver or in the lymph nodes causing pain and leading to nausea.
If the leukemic cells invade the central nervous system, then neurological symptoms can occur. Uncommon neurological symptoms like migraines, seizures, or coma can occur as a result of brain stem pressure. All symptoms associated with leukemia can be attributed to other diseases. Consequently, leukemia is always diagnosed through medical tests.
The word leukemia, which means 'white blood', is derived from the characteristic high white blood cell count that presents in most affected people before treatment. The high number of white blood cells is apparent when a blood sample is viewed under a microscope, with the extra white blood cells frequently being immature or dysfunctional. The excessive number of cells can also interfere with the level of other cells, causing further harmful imbalance in the blood count.
Some people diagnosed with leukemia do not have high white blood cell counts visible during a regular blood count. This less-common condition is called aleukemia. The bone marrow still contains cancerous white blood cells that disrupt the normal production of blood cells, but they remain in the marrow instead of entering the bloodstream, where they would be visible in a blood test. For a person with aleukemia, the white blood cell counts in the bloodstream can be normal or low. Aleukemia can occur in any of the four major types of leukemia, and is particularly common in hairy cell leukemia.