Acute leukemia is a tumor lesion of the hematopoietic system, the morphological basis of which are immature (blast) cells that displace normal hematopoietic sprouts. Clinical symptoms are represented by progressive weakness, unmotivated fever, arthralgias and ossalgias, bleeding of various localizations, lymphadenopathy, hepatosplenomegaly, gingivitis, stomatitis, angina. To confirm the diagnosis, it is necessary to examine the hemogram, bone marrow punctate, iliac bone biopsy and lymph nodes. The basis of treatment is chemotherapy courses and accompanying therapy.
Acute leukemia is a form of leukemia in which normal bone marrow hematopoiesis is displaced by poorly differentiated leukocyte progenitor cells with their subsequent accumulation in peripheral blood, infiltration of tissues and organs. The terms “acute leukemia” and “chronic leukemia” reflect not only the duration of the disease, but also the morphological and cytochemical characteristics of tumor cells. Pathology is the most common form of hemoblastosis: it develops in 3-5 out of 100 thousand people; the ratio of adults and children is 3:1. At the same time, people over 40 years of age are statistically more likely to be diagnosed with acute myeloid leukemia, and children with acute lymphoblastic leukemia.
The root cause of disease is a mutation of a hematopoietic cell that gives 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 hematopoiesis sprouts in the bone marrow, and later enter the bloodstream and spread to various tissues and organs, causing their leukemic infiltration. All blast cells carry the same morphological and cytochemical characteristics, which indicates in favor of their clonal origin from a single ancestral cell.
The reasons triggering 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 in the family practically triples the risk of the disease in close relatives. The risk of disease increases with certain chromosomal abnormalities and genetic pathologies – Down’s disease, Klinefelter syndrome, Wiskott-Aldrich and Louis-Barre, Fanconi anemia, etc.
It is likely that the activation of genetic predisposition occurs under the influence of various exogenous factors. The latter may include ionizing radiation, chemical carcinogens (benzene, arsenic, toluene, etc.), cytostatic drugs used in oncology. Often acute leukemia becomes a consequence 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 has been noted; concomitant hematological diseases (some forms of anemia, myelodysplasia, paroxysmal nocturnal hemoglobinuria, etc.).
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-differentiated precursors of lymphocytes) and non-lymphoblastic (combining other forms).
1. Acute lymphoblastic leukemias of adults and children:
- neither T nor V-form
2. Acute non-lymphoblastic (myeloid) leukemias:
- myeloblastic (caused by uncontrolled proliferation of granulocyte precursors)
- mono- and myelomonoblastic (characterized by increased proliferation of monoblasts)
- megakaryoblastic (associated with the predominance of undifferentiated megakaryocytes – precursors of platelets)
- erythroblastic (caused by proliferation of erythroblasts)
3. Acute undifferentiated leukemia.
The course of acute leukemia goes through a number of stages:
- I (initial) – general nonspecific symptoms prevail.
- II (expanded) – characterized by pronounced clinical and hematological symptoms of hemoblastosis. Includes: debut or first “attack”, incomplete or complete remission, relapse or recovery
- III (terminal) – characterized by deep depression of normal hematopoiesis.
The manifestation of acute leukemia may be sudden or erased. Typically, the onset is characterized by high fever, intoxication, sweating, a sharp decline in strength, anorexia. During the first “attack”, patients note persistent pain in muscles and bones, arthralgia. Sometimes the initial stage of acute leukemia is masked as ARI or angina; the first signs of leukemia may be ulcerative stomatitis or hyperplastic gingivitis. Quite often, the disease is detected accidentally during a preventive hemogram examination or retrospectively when acute leukemia passes into the next stage.
In the extended period of acute leukemia, anemia, hemorrhagic, intoxication and hyperplastic syndromes develop.
Anemic manifestations are caused by a violation of the synthesis of red blood cells, on the one hand, and increased bleeding, on the other. They include pallor of the skin and mucous membranes, constant fatigue, dizziness, palpitations, increased hair loss and brittle nails, etc. The severity of tumor intoxication increases. In conditions of absolute leukopenia and a decline in immunity, various infections are easily joined: pneumonia, candidiasis, pyelonephritis, etc.
The hemorrhagic syndrome is based on pronounced thrombocytopenia. The range of hemorrhagic manifestations ranges from small single petechiae and bruises to hematuria, gingival, nasal, uterine, gastrointestinal bleeding, etc. As acute leukemia progresses, bleeding can become more massive due to the development of DIC syndrome.
Hyperplastic syndrome is associated with leukemic infiltration of both the bone marrow and other organs. In patients with acute leukemia, there is an increase in lymph nodes (peripheral, mediastinal, intra-abdominal), hypertrophy of the tonsils, hepatosplenomegaly. Leukemic infiltrates of the skin (leukemides), the membranes of the brain (neuroleukosis), damage to the lungs, myocardium, kidneys, ovaries, testicles, etc. may occur. organs.
Complete clinical and hematological remission is characterized by the absence of extra-spinal leukemic foci and the content of blasts in the myelogram is less than 5% (incomplete remission is less than 20%). The absence of clinical and hematological manifestations for 5 years is regarded as recovery. In the case of an increase in blast cells in the bone marrow of more than 20%, their appearance in peripheral blood, as well as the detection of extra-bone marrow metastatic foci, a relapse of acute leukemia is diagnosed.
The terminal stage of acute leukemia is established with the ineffectiveness of chemotherapeutic treatment and the impossibility of achieving clinical and hematological remission. Signs of this stage are the progression of tumor growth, the development of life-incompatible disorders of the function of internal organs. The described clinical manifestations are joined by hemolytic anemia, recurrent pneumonia, pyoderma, abscess and phlegmons of soft tissues, sepsis, progressive intoxication. The cause of death of patients are uncoupled bleeding, brain hemorrhages, infectious and septic complications.
At the head of the diagnosis of acute leukemia is the assessment of the morphology of peripheral blood cells and bone marrow. The hemogram for leukemia is characterized by anemia, thrombocytopenia, high ESR, leukocytosis (less often 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 type of acute leukemia, a sternal puncture is performed with morphological, cytochemical and immunophenotypic examination of the bone marrow. When examining the myelogram, attention is drawn to an increase in the percentage of blast cells (from 5% and above), lymphocytosis, inhibition of the red germ of hematopoiesis (except in cases of acute erythromyelosis) and an absolute decrease or absence of megakaryocytes (except in cases of acute megakaryoblastic leukemia). Cytochemical marker reactions and immunophenotyping of blast cells make it possible to accurately determine the form of acute leukemia. If the interpretation of the bone marrow analysis is ambiguous, trepanobiopsy is resorted to.
In order to exclude leukemic infiltration of internal organs, a spinal puncture is performed with a study of the cerebrospinal fluid, skull and chest x-ray, 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, it may be necessary to study the coagulogram, biochemical blood analysis, electrocardiography, EchoCG, etc.
Differential diagnostic measures are aimed at excluding HIV infection, infectious mononucleosis, cytomegalovirus infection, collagenoses, thrombocytopenic purpura, agranulocytosis; pancytopenia in aplastic anemia, B12 and folic deficiency anemia; leukemoid reactions in whooping cough, tuberculosis, sepsis and other diseases.
Patients with acute leukemia are treated in oncohematological hospitals. An enhanced sanitary and disinfection regime is organized in the wards. Patients with acute leukemia need hygienic treatment of the oral cavity, prevention of bedsores, toilet of the genitals after physiological exercises; organization of high-calorie and fortified nutrition.
The treatment of acute leukemia is carried out sequentially; the main stages of therapy include achieving (induction) remission, its consolidation and maintenance, prevention of complications. For this purpose, standardized schemes of polychemotherapy have been developed and 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 polychemotherapy are carried out. Supportive anti-relapse therapy is carried out for at least 3 more years. Along with chemotherapy for acute leukemia, it is necessary to conduct accompanying treatment aimed at preventing agranulocytosis, thrombocytopenia, DIC syndrome, infectious complications, neuroleukemia (antibiotic therapy, transfusion of erythrocyte, platelet mass and freshly frozen plasma, endolumbal administration of cytostatics). With leukemic infiltration of the pharynx, mediastinum, testicles, etc. organs are undergoing radiotherapy of lesions.
In case of successful treatment, the destruction of a clone of leukemic cells is achieved, normalization of hematopoiesis, which contributes to the induction of a long relapse-free period and recovery. To prevent relapses of acute leukemia, bone marrow transplantation can be performed after pre-conditioning by chemotherapy and total irradiation.
According to available statistical data, the use of modern cytostatic agents leads to the transition of acute leukemia into 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.
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