Acute lymphoblastic leukemia causes symptoms treatment

Acute leukemia is a form of leukemia in which normal bone marrow hematopoiesis is replaced by slightly differentiated leukocyte precursor cells with their subsequent accumulation in peripheral blood, and tissue and organ infiltration. The terms “acute leukemia” and “chronic leukemia” reflect not only the duration of the course of the disease, but also the morphological and cytochemical characteristics of the tumor cells.

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The specificity of malignant neoplasms as a whole boils down to a pathology accompanied by the formation of cells, whose division occurs in an uncontrolled manner with the subsequent ability to invade (i.e., invade) the tissues adjacent to them. At the same time, they also have the opportunity of metastasis (or movement) to organs located at a certain distance from them. This pathology is directly related to the growth of tissue, and to cell division that arose due to one or another type of genetic disorder.

As for lymphocytic leukemia, it, as we have already noted, is a malignant disease, while the proliferation of lymphoid tissue occurs in the lymph nodes, in the bone marrow, in the liver, in the spleen, as well as in some other types of organs. Diagnosis of pathology is predominantly observed in the Caucasian race, and for every one hundred thousand people, about three cases of the disease occur annually.

The existing classification, which determines the course and specificity of the disease, distinguishes two forms of lymphocytic leukemia: acute (lymphoblastic) leukemia and chronic leukemia (lymphocytic leukemia).

What is Acute lymphoblastic leukemia

Acute lymphoblastic leukemia is a group of heterogeneous malignant neoplasms from cells – lymphoid precursors (lymphoblasts), which have certain genetic and immunophenotypic characteristics.

Acute lymphoblastic leukemia is the most common leukemia in childhood and adolescence. The peak incidence occurs at the age of 1 year to 6 years. They occur with damage to the bone marrow, lymph nodes, spleen, thymus gland, as well as other organs.

The genetic basis for the development of acute lymphoblastic leukemia is based on changes in the structure of chromosomes, i.e. chromosomal aberrations. With leukemia, specific or primary and nonspecific aberration chromomonoms are distinguished. The primary ones include translocation, deletion, inversion, amplification of chromosome regions containing oncogenes, genes of cell receptors, genes of growth factors.

Such changes are capable of forming new DNA sequences and the appearance of new properties in the cell, the formation of a specific clone. Secondary chromosomal aberrations appear at the stage of tumor progression as a result of changes in the formed clone. Moreover, similar aberrations can be observed with different variants of leukemia. So, the Philadelphia chromosome can be detected in both acute and chronic leukemia.

The reasons for the development of acute lymphoblastic leukemia in children are still not precisely established, however, there is evidence of a large importance of infectious diseases in infancy, the effects of various physical ones (for example, X-ray diagnostics, radiation therapy, ionizing radiation), the effect of chemical mutagens.

when exposed to benzene, among patients receiving cytostatic immunosuppressants (imuran, cyclophosphamide, leukaran, sarcolysin, mustargen, etc.), biological (viral) mutagens on the mother’s body during pregnancy. The relationship between many congenital chromosomal abnormalities and the development of acute leukemia has also been proven.

In bone marrow, peripheral blood, and in other organs, tumor cells such as lymphoblasts with SIK-positive granules in the cytoplasm are found that do not give reactions to peroxidase, esterases, and do not contain lipids.

In 2/3 cases, cytogenetic disorders in the form of polyploidy, the Philadelphia chromosome and reciprocal translocation between the chromosomes are detected in the tumor cells.

The cytogenesis of acute lymphoblastic leukemia is associated with the precursors of T and B lymphocytes. T-cell leukemia in Europe accounts for 10-15% of cases. B-cell leukemia predominates.

Guided by the immunological phenotypes of tumor cells, several forms of lymphoblastic leukemia are distinguished, which is important for the choice of therapy and prognosis. The predominant B-lymphoblastic leukemia is represented by early, intermediate and late variants, differing in the expression of CD10 paraglobulin, surface immunoglobulin and terminal dioxinucleotide transferase activity. Markers of T-lymphoblastic leukemia are CD7 and T-receptor antigens.

There are two types of acute lymphoblastic leukemia: B-linear and T-linear, depending on the type of cells – lymphoid precursors.

All white blood cells in the human body are divided into 2 types – granulocytic and agranulocytic (granular and non-granular), these two groups, in turn, are divided into eosinophils, basophils, neutrophils (granulocytic), and lymphocytes (B and T types) and monocytes (agranulocytic). In the process of maturation and development (differentiation), all cells go through several stages, the first of which is the blast stage (lymphoblasts).

Relatively recently, it was considered a “childhood” disease due to the susceptibility to it mainly of small patients aged two to four years. Currently observed among adults.

The exact causes of the disease are still unknown to scientists.

But there are certain risk factors, including:

  • age;
  • gender (in men, the disease is more common than in women);
  • Belonging to the white race, (blacks are less susceptible to this disease);
  • previous cancer treatment and radiation;
  • the presence of genetic disorders (Down Syndrome).

Chronic lymphocytic leukemia, represented by T-lymphocytes, occurs in approximately 5% of cases.

This is a tumor from CD4 lymphocytes caused by human T-lymphotropic virus type 1 (HTLV-I). The disease is manifested by a generalized (spreading throughout the body) swollen lymph nodes and skin lesions. Due to immunodeficiency, the frequency of secondary infections is very high.

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Men get sick more often than women. For treatment, various combinations of antitumor agents are used.

Causes of Acute Leukemia

The root cause of acute leukemia is a mutation of the hematopoietic cell, giving rise to a tumor clone. Mutation of the hematopoietic cell leads to a violation of its differentiation at an early stage of immature (blast) forms with further proliferation of the latter. The resulting tumor cells replace normal hematopoietic sprouts in the bone marrow, and subsequently enter the bloodstream and spread to various tissues and organs, causing their leukemic infiltration. All blast cells carry the same morphological and cytochemical characters, which indicates in favor of their clonal origin from one parent cell.

The reasons that trigger the mutation process are not known. In hematology, it is customary to talk about risk factors that increase the likelihood of developing acute leukemia. First of all, this is a genetic predisposition: the presence of patients with acute leukemia in the family almost triples the risk of the disease in close relatives. The risk of acute leukemia increases with certain chromosomal abnormalities and genetic pathologies – Down’s disease, Klinefelter’s syndrome, Wiskott-Aldrich and Louis-Barr, Fanconi anemia, etc.

It is likely that the activation of a genetic predisposition occurs under the influence of various exogenous factors. Among the latter can be ionizing radiation, chemical carcinogens (benzene, arsenic, toluene, etc.), cytostatic drugs used in oncology. Often, acute leukemia becomes the result of antitumor therapy of other hemoblastoses – lymphogranulomatosis, non-Hodgkin’s lymphomas, myeloma. The connection of acute leukemia with previous viral infections that depress the immune system is noted; concomitant hematological diseases (some forms of anemia, myelodysplasia, paroxysmal nocturnal hemoglobinuria, etc.).

Classification of Acute Leukemia

In oncohematology, the international FAB classification of acute leukemia is generally accepted, differentiating various forms of the disease depending on the morphology of tumor cells into lymphoblastic (caused by low-grade lymphocyte precursors) and non-lymphoblastic (combining other forms).

1. Acute lymphoblastic leukemia in adults and children:

2. Acute non-lymphoblastic (myeloid) leukemia:

  • about. myeloblastic (caused by uncontrolled proliferation of granulocyte precursors)
  • about. mono and about. myelomonoblastic (characterized by enhanced reproduction of monoblasts)
  • about. megakaryoblastic (associated with the predominance of undifferentiated megakaryocytes – platelet precursors)
  • about. erythroblast (due to proliferation of erythroblasts)

3. Acute undifferentiated leukemia.

The course of acute leukemia passes through a number of stages:

  • I (initial) – general non-specific symptoms prevail.
  • II (detailed) – characterized by clearly expressed clinical and hematological symptoms of hemoblastosis. Includes: debut or first “attack”, incomplete or complete remission, relapse or recovery
  • III (terminal) – characterized by deep inhibition of normal hematopoiesis.

Treatment

Today, there are several ways to treat acute leukemia:

  • chemotherapy – therapy with potent chemotherapy drugs. Medications can be taken orally (in the form of tablets, capsules) or the patient is given intravenous or intramuscular injections;
  • radiation therapy – a method of treating cancer in which the doctor uses x-rays or other types of radiation;
  • stem cell transplantation, which is used to replace abnormal blood-forming cells with full ones.

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All these methods have been successfully applied at the ON CLINIC International Medical Center, where over the years highly qualified doctors have saved thousands of lives of patients with lymphoblastic leukemia.

Patients with acute leukemia are treated in oncohematological hospitals. In the chambers, an enhanced sanitary and disinfection regime is being organized. Patients with acute leukemia need hygienic treatment of the oral cavity, the prevention of pressure sores, and the toilet of the genitals after physiological administration; organization of high-calorie and fortified nutrition.

Direct treatment of acute leukemia is carried out sequentially; The main stages of therapy include the achievement (induction) of remission, its consolidation (consolidation) and maintenance, prevention of complications. For this, standardized chemotherapy regimens have been developed and are being used, which are selected by a hematologist taking into account the morphological and cytochemical forms of acute leukemia.

In a favorable situation, remission is usually achieved within 4-6 weeks of enhanced therapy. Then, as part of the consolidation of remission, another 2-3 courses of chemotherapy are carried out. Supportive anti-relapse therapy is carried out for at least 3 years. Along with chemotherapy for acute leukemia, accompanying treatment is necessary to prevent agranulocytosis, thrombocytopenia, DIC, infectious complications, neuroleukemia (antibiotic therapy, transfusion of red blood cells, platelet mass and fresh frozen plasma, endolumbar administration of cytostatics). With leukemic infiltration of the pharynx, mediastinum, testicles and other organs, x-ray therapy of the lesions is performed.

In case of successful treatment, destruction of the clone of leukemic cells, normalization of hematopoiesis is achieved, which contributes to the induction of a long relapse-free period and recovery. To prevent relapse of acute leukemia, bone marrow transplantation can be performed after preconditioning by chemotherapy and total radiation.

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According to available statistics, the use of modern cytostatic agents leads to the transition of acute leukemia to the remission phase in 60-80% of patients; 20-30% of them manage to achieve full recovery. In general, the prognosis for acute lymphoblastic leukemia is more favorable than for myeloblastic.

A feature of the treatment of lymphocytic leukemia is that experts agree on the inappropriateness of its implementation at an early stage. This is due to the fact that most patients during the initial stages of the disease carry it in a “smoldering” form. Accordingly, for a long time you can do without the need for taking medications, and also live without any restrictions, while being in a relatively good condition.

Therapy is performed for chronic lymphocytic leukemia, and only if there is reason for this in the form of characteristic and vivid manifestations of the disease. So, the feasibility of treatment arises if there is a rapid increase in the number of lymphocytes, as well as with the progression of an increase in lymph nodes, a rapid and significant increase in the spleen, anemia and thrombocytopenia.

Treatment is also necessary if signs of tumor intoxication occur. They consist in increased sweating at night, in rapid weight loss, constant weakness and fever.

Today, chemotherapy is actively used for treatment. Until recently, chlorobutin was used for the procedures, but now the greatest effectiveness of treatment is achieved using purine analogues. A topical solution is bioimmunotherapy, the method of which involves the use of monoclonal antibodies. Their introduction provokes selective destruction of tumor cells, but damage to healthy tissues does not occur.

In the absence of the required effect in the use of these methods, the doctor prescribes high-dose chemotherapy, providing for the subsequent transplantation of hematopoietic stem cells. In the presence of a significant tumor mass, the patient uses radiation therapy, which acts as an adjunct therapy in treatment.

A strong enlargement of the spleen may require complete removal of this organ.

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Diagnosing a disease requires contact with specialists such as a therapist and hematologist.

Diagnosis of acute leukemia

Diagnosis of acute leukemia is led by an assessment of the morphology of peripheral blood cells and bone marrow. The hemogram for leukemia is characterized by anemia, thrombocytopenia, high ESR, leukocytosis (less commonly leukopenia), the presence of blast cells. The phenomenon of “leukemic gaping” is indicative – there are no intermediate stages between blasts and mature cells.

In order to confirm and identify the variety of acute leukemia, sternal puncture is performed with morphological, cytochemical and immunophenotypic studies of the bone marrow. In the study of myelograms, an increase in the percentage of blast cells (from 5% and above), lymphocytosis, inhibition of the red sprout of hematopoiesis (except for cases of o. erythromyelosis) and an absolute decrease or absence of megakaryocytes (except for cases of about megakaryoblastic leukemia) are noteworthy. Cytochemical marker reactions and immunophenotyping of blast cells can accurately establish the form of acute leukemia. With ambiguities in the interpretation of bone marrow analysis, they resort to trepanobiopsy.

In order to exclude leukemic infiltration of internal organs, a spinal puncture is performed with a cerebrospinal fluid examination, X-ray of the skull and chest organs, ultrasound of the lymph nodes, liver and spleen. In addition to a hematologist, patients with acute leukemia should be examined by a neurologist, ophthalmologist, otolaryngologist, dentist. To assess the severity of systemic disorders, a coagulogram study, a biochemical blood test, electrocardiography, echocardiography, etc.

Differential diagnostic measures are aimed at eliminating HIV infection, infectious mononucleosis, cytomegalovirus infection, collagenoses, thrombocytopenic purpura, agranulocytosis; pancytopenia with aplastic anemia, B12 and folic acid deficiency anemia; leukemoid reactions with whooping cough, tuberculosis, sepsis and other diseases.

Forecast

Without treatment, lymphocytic leukemia can lead to the death of the patient within a few months or even weeks. With timely treatment, about 40-50% of adult patients manage to achieve a stable remission – that is, no cancer recurrence for five or more years, after which the person can be considered healthy.

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Svetlana Borszavich

General practitioner, cardiologist, with active work in therapy, gastroenterology, cardiology, rheumatology, immunology with allergology.
Fluent in general clinical methods for the diagnosis and treatment of heart disease, as well as electrocardiography, echocardiography, monitoring of cholera on an ECG and daily monitoring of blood pressure.
The treatment complex developed by the author significantly helps with cerebrovascular injuries and metabolic disorders in the brain and vascular diseases: hypertension and complications caused by diabetes.
The author is a member of the European Society of Therapists, a regular participant in scientific conferences and congresses in the field of cardiology and general medicine. She has repeatedly participated in a research program at a private university in Japan in the field of reconstructive medicine.

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