Generality
Leukemia is a term that includes a series of malignant diseases, commonly called "blood cancers"; these are neoplastic hyperproliferations affecting hematopoietic stem cells, bone marrow and the lymphatic system.
Another important classification depends on the cells from which the neoplasia originates: we speak of lymphoid leukemia (or lymphocytic, lymphoblastic, lymphatic), when the tumor affects the intermediate precursors of T or B lymphocytes and myelogenous leukemia (or myelocytic, granulocytic), when, on the contrary, the degeneration concerns the common progenitor of granulocytes, monocytes, erythrocytes and platelets.
Based on these considerations, we will have four common types of leukemia: chronic myeloid leukemia (CML) and acute myeloid leukemia (AML); chronic lymphatic leukemia (CLL, also called lymphocytic) and acute lymphatic leukemia (ALL, also called lymphoblastic).
Causes
The causes of leukemia are not known, although it is now clear that the disease, like other tumors, constitutes the final result of a complex series of events, which involve both constitutional genetic factors and environmental factors (ionizing radiations, toxic substances such as benzene derivatives, infectious agents ...). The uncontrolled proliferation of leukemic cells is the result of an abnormality affecting the DNA, which - as in other types of neoplasia - determines an alteration of the mechanisms of regulation and control of growth and cell differentiation. These processes are regulated by specific genes which, if damaged, can determine the transformation of a cell from normal to neoplastic, according to only partially known events.
Although the causes are not yet completely clear, some myelotoxic agents (benzene, alkylating agents and ionizing radiation) have been identified with certainty that can promote leukemogenesis.
The main risk factors, which can facilitate the onset of leukemia, are:
- Exposure to high doses of ionizing radiation, which can occur by:
- Radiotherapy : the incidence is very high in subjects treated with radiotherapy for other neoplasms; in this case blood cancers are defined as secondary.
- Atomic accidents : to remember is the tragic balance between the survivors of the atomic explosions of Hiroshima and Nagasaki, exposed to high doses of radiation and severely affected by leukemia.
- Occupational exposure : it is possible that there is an association between leukemia and prolonged exposure to radiation, certain chemicals in the workplace and at home, or low-frequency electromagnetic fields; however, there is still no definitive evidence to prove its close correlation.
- Benzene : used in the chemical industry, present in oil and gasoline. Its prolonged inhalation is associated initially with hematologic dyscrasia (alteration of the ratios of the elements that make up blood or other organic liquids), which can degenerate into leukemia. In order to exert a mutagenic and carcinogenic action, benzene must undergo oxidative conversion and become reactive intermediates that react covalently with DNA, causing interference with nucleic acid replication and repair processes.
- Taking antiblastic, type II topoisomerase inhibitors and some chemotherapy drugs may increase the risk of secondary leukemia (especially in combination with radiotherapy). The drugs that induce greater susceptibility are the alkylating agents (chlorambucil, nitrosoureas, cyclophosphamide).
- Smoking can contribute to the onset of some forms of leukemia (1/4 of all acute myeloid leukemias occur among smokers), due to the presence of some substances contained in the cigarette, such as benzopyrene, toxic aldehydes and certain heavy metals (example : cadmium and lead).
- Some hereditary diseases - such as Down syndrome or chromosomal instability syndromes - are linked to a 10-20 times higher risk of developing leukemia in the first ten years of life. In some of these diseases, the genetic mutation directly involves particular proteins involved in DNA repair processes. The risk of developing a leukemia is therefore correlated to a lower cellular efficiency in the protection mechanisms in case of genetic alterations.
- Myelodysplasia ( preleukemic pathology) and other predisposing blood disorders : render more susceptible to the onset of acute myeloid leukemia.
- Type 1 human T lymphocyte virus ( HTLV-1 ): a class of oncogenic retroviruses (classified as oncovirus), also referred to as human T-cell leukemia viruses ( Human T-cell Leukemia Virus ), capable of to cause, in rare cases, leukemias and adult lymphomas, and promote cell proliferation in an indirect way: the virus replicates slowly and remains latent for a long time in the infected cells, mainly T lymphocytes. Infection with HTLV-1 is implicated in particular in chronic lymphoblastic leukemia (LLC).
- Family transmission : only in rare cases a patient with leukemia (chronic lymphatic, in particular) has a parent, brother or child affected by the same disease.
Exposure to one or more risk factors potentially implicated in leukemogenesis does not necessarily cause the onset of the disease. Moreover, it is essential to remember that in the pathogenesis of different types of leukemia specific chromosomal alterations occur, which allow us to characterize the different neoplastic forms, such as the translocation t (9; 22), with formation of the Philadelphia chromosome, in chronic myeloid leukemia or the trisomy of chromosome 12, common in patients with chronic lymphocytic leukemia. During the diagnosis, the identification of specific aberrations on genes and chromosomes, using conventional cytogenetic techniques, in situ hybridization or molecular biology, makes it possible to identify the leukemia subtype and guide towards the therapeutic choice.
Symptoms
To learn more: Symptoms Leukemia
The disorders and symptoms of leukemia can vary in each patient, depending on the type and amount of cancer cells, and the severity of the disease. In some cases, in the early stages the symptoms may be non-specific and could be caused by other concomitant diseases.
Due to the proliferative advantage of leukemic cells, a clonal expansion takes place which occupies a large part of the bone marrow and pours into the bloodstream. The invasive character of neoplastic clones also allows their spread to the lymphatic glands or other organs (example: spleen) and can cause swelling or pain in various parts of the body.
Patients with chronic leukemia can be asymptomatic and the doctor can detect the clinical signs during a routine blood test, while the subjects who manifest an acute form of the disease often undergo a medical examination due to a sensation general malaise.
Therefore, the general symptoms that can develop include:
- Fatigue and general malaise ( asthenia ), caused by the reduced production of red blood cells;
- Vague abdominal disorders, with loss of appetite and weight ;
- Fever, due to the disease itself or to a concomitant infection (favored by the drop in white blood cells by the bone marrow) ;
- Joint or muscle pain (in the case of considerable tumor mass). Furthermore, a characteristic bone pain may occur due to the compression exerted by the expanding bone marrow;
- Excessive sweating, especially at night;
- Dyspnea (from lack of red blood cells), palpitations (from anemia).
Symptoms caused by the infiltration of blasts in the bone marrow:
- Tendency to have ecchymoses or bleeding (due to decreased platelet production, the blood elements responsible for coagulation). Generally, blood loss is mild and typically occurs at the level of skin and mucous membranes, with bleeding from the gums, nose or due to the presence of blood in the stool or urine;
- Increased susceptibility to infections, usually caused by decreased production of functioning leukocytes. Infections can affect every organ or system and are accompanied by headache, low-grade fever and rash;
- Anemia and related symptoms such as weakness, easy fatigability and skin pallor.
Leukemia symptoms caused by infiltration in other organs and / or tissues:
- Lymphadenopathy (swelling of the lymph nodes) especially latero-cervical, axillary, inguinal;
- Pain in the left side (under the costal arch) due to enlargement of the spleen ( splenomegaly );
- Possible enlargement of the liver;
- Infiltration of the central nervous system (rare): leukemic cells can invade the brain, spinal cord or meninges. If such an event is required, the patient can observe:
- Headache, whether or not associated with nausea and vomiting;
- Changes in the perception of sensitivity, such as numbness or tingling in various parts of the body;
- Paralysis of the cranial nerves, with impaired vision, falling of the eyelid, deviation of the corner of the mouth.
In the advanced stages the accentuation of the above symptoms can occur and the clinical manifestations of leukemia may include:
- Sudden fever rises;
- Altered state of consciousness;
- Convulsions;
- Inability to speak or move limbs.
In the event of symptoms such as high fever, sudden bleeding or convulsions occurring without apparent cause, emergency treatment for acute leukemia is essential.
If there are signs of recurrence, such as an infection or hemorrhage, during the disease remission phase (attenuation or disappearance of the symptoms of a disease), a medical check-up is required.
Incidence
The pathology tends to manifest itself in the first decade of age, as far as acute leukemia is concerned, while the chronic forms afflict more subjects of adult age and develop especially after the age of 40, with a greater frequency in relation to the increase in age. Acute leukemia, in particular, accounts for 25% of all children's cancers.
The overall incidence is around 15 out of 100, 000 people each year.
| Course | Incidence | |
| Chronic lymphatic leukemia (LLC) | Generally, it progresses very slowly. | CLL is the most frequently observed form in western industrialized countries and represents 25-35% of all human leukemias, with an annual incidence of 5-15 cases per 100, 000 inhabitants (male / female ratio 2: 1); the LLC prefers elderly people over the age of 50 (peak incidence: 60-70 years). |
| Chronic myeloid leukemia (CML) | In the initial chronic phase it evolves very slowly, to then undergo a transformation into acute leukemia, through an accelerated transition phase of about 3-6 months. | CML is the most frequent of myeloproliferative syndromes; represents 15-20% of all cases of leukemia and has an incidence of 1-2 cases per 100, 000 individuals per year. The greatest incidence is observed after the age of 50 (range: 25-70 years), mainly affects the male sex and is very rare in children. |
| Acute lymphoblastic leukemia (ALL) | It develops very quickly. | It represents 80% of leukemias in children and young people under the age of 15, while it represents 20% of adult leukemic forms. About 80% of ALL are represented by malignant proliferations of the B chain, while 20% include cadres resulting from the involvement of precursors of the T chain. |
| Acute myeloid leukemia (AML) | It has a very rapid course. | Estimated incidence around 3.5 cases per 100, 000 individuals per year. It can occur at any age, but its frequency increases with increasing age. Indeed, AMLs constitute almost all of the acute leukemias of the elderly. |
