Acute blood leukemia (in common parlance, leukemia) is the development of a malignant neoplasm, during which the functionality of the bone marrow is impaired, causing a decrease in the production of erythrocytes (red blood cells), which are subsequently replaced by immature leukocytes (myeloblasts).

Previously, it was almost impossible to cure the disease, and in many cases the patient died. The only cure for leukemia was bone marrow transplantation. Now the appearance of this disease is no longer so scary, thanks to the development of modern medicine.

According to statistics, such a disease is considered rare: no more than 35 cases of acute leukemia in adults and children per 1 million people are recorded annually.

Classification of leukemia

In modern times, there are two types of acute leukemia: myeloblastic (AML) and lymphoblastic (ALL). The myeloblastic type of disease is characterized by rapid growth of immature leukocytes; with prolonged development of the disease, mutation of myeloblasts occurs and their further transformation into other substances: eosinophil, basophil, or neutrophil. With the development of this form of the disease, the following are distinguished:

• acute form of non-lymphoblastic leukemia;
• myeloblastic without maturation;
• megakaryoblastic leukemia;
• erythroleukemia;
• monoblastic leukemia.

Although some of these types of adult leukemia are considered separate diseases, the only difference between them is chemical feature. ALL – cancer circulatory system, which is characterized by rapid development. In the absence of proper therapy within 3-6 months, cancer cells will affect all internal organs, and the disease will end in death.

Factors in the development of acute leukemia

When identifying acute leukemia in adults, it is important to establish the factor that triggered the development of the dangerous disease. The exact causes of the development of this oncology have not been identified, but there are some risk factors that may lead to the occurrence of the disease:

• people exposed to radiation;
• if a person was injured after a nuclear explosion;
• during radiotherapy treatment;
• frequent x-rays (more than 2-3 times a year);
• frequent smoking with large amounts of nicotine consumption;
• HIV and other autoimmune diseases;
• Down syndrome and other chromosomal mutations;
• professional activity in chemical or industrial production;
• carrying out chemotherapy;
• if close relatives have been diagnosed with leukemia in their life history.

If in human life There are similar risk factors, this does not mean that he will be diagnosed with acute leukemia, it is quite possible that everything will work out. But it would still be useful to consult a specialist.

Symptoms that should prompt you to consult a doctor

Due to the fact that at the initial stage of development, leukemia is similar in symptoms to many colds, it is almost impossible to recognize it at an early stage. In acute leukemia, symptoms of a characteristic type are detected already at an advanced stage of the disease. These include:

• the appearance of bloody discharge from the nose and gums, without any reason;
• localization of deep red spots on the skin or the formation of small bruises;
• temperature fluctuations, accompanied by general malaise and fever;
• significant enlargement of some internal organs (liver, spleen) and lymph nodes;
• susceptibility to even minor infections;
• aches in the area of ​​joint tissue;
• anemia, which may be accompanied by attacks of nausea and dizziness;
• heavy sweating, increasing during the night's rest;
• loss of appetite, which can lead to complete refusal of food;
• sudden loss of body weight.

And also when conducting general and biochemical blood screening, when deciphering the analysis, a high content of leukocytes is observed.

Diagnostic methods for blood cancer

This disease can be detected even by a general or biochemical blood test. With the development of oncology, the level of leukocytes in the blood will be excessively high, and red blood cells and platelets will be reduced to minimal levels. An increased content of blast cells is diagnosed in the blood. But still, to make an accurate diagnosis, it is necessary to undergo additional examination:

• morphological – necessary for accurately determining the level of blast cells;
• cytochemical – allow us to identify the nature of cancer cells;
• cytogenetic – necessary to determine the structural features of chromosomes in pathological cells;
• immunophenotyping – carried out to determine the localization of pathogenic cells and the form of cancer;
• Cerebrospinal fluid studies are necessary to determine the stage of central nervous system damage.

Except laboratory methods research, additional examination is also used using specialized equipment: ultrasound, CT, etc. Similar methods examinations make it possible to identify the exact stage and form of development of an oncological disease; this information is very important in order to carry out competent treatment of acute leukemia.

The methods of treatment used and the system for their implementation

Once the diagnosis has been made and the stage has been identified, the factors for the development of blood cancer need to be diagnosed as early as possible, since this disease has the characteristic of rapid progression. It is possible that a relapse may occur after incorrectly prescribed therapy. Most often, chemotherapy is used in treatment, in which the drugs used destroy pathogenic cells in the body.

The dosage of medications is selected individually for each person based on the characteristics of the body. Treatment is aimed at destroying pathological cells while preserving healthy bone marrow cells. As a rule, therapy is carried out in three stages:

• therapy to achieve remission (in medical terminology it is called “induction of remission”). Usually, to achieve the desired effect, intensive treatment is used using the strongest chemotherapy drugs. In the first month of treatment, a specialist may prescribe glucocorticosteroid hormones; the doctor will select the drug based on the stage of development, but the most common are: Vincristine, Asparaginase. When the remission stage is reached, the level of pathogenic cells in the bone marrow should not exceed 5%;
• treatment to consolidate the stage of remission. As a rule, this stage of treatment lasts for several months. It aims to completely destroy the remaining pathogenic cells. Invasive chemotherapy is usually prescribed. All actions are carried out under the supervision of an oncologist. The dosage of the drug depends on the characteristics of the body and the form of the disease. Typically used similar drugs: “Asparaginase”, “Cyclophosphamide”;
• Maintenance treatment is carried out over several years. Therapy is aimed at eliminating possible relapse. This period is very important and you must follow all the specialist’s instructions. At this stage of treatment, the following are used: Mercaptopurine and Methotrexate.

According to statistics, a person suffering from blood cancer, without the necessary treatment, will die in just a few weeks or 1-2 months, but with proper therapy he can extend his life by 10-20 years, without losing its quality. Thanks to the development of modern medicine, surgical (bone marrow transplantation) methods of treatment are used extremely rarely; now more gentle methods of therapy are used.

Informative video

Leukemia is a whole group of malignant diseases of the hematopoietic system. All diseases of this group have a common characteristic, which is that malignant clones are formed from hematopoietic cells of the bone marrow.

Symptoms

The clinical picture is the same for all types of leukemia. The onset of the disease may be sudden. The serious condition of the patient upon admission to the hospital may be due to severe intoxication, hemorrhagic syndrome(the result of thrombocytopenia), respiratory failure (due to compression of the respiratory tract by enlarged intrathoracic lymph nodes).

Source www.medmoon.ru

Causes

Doctors call leukemia a multifactorial disease, that is, today a very large number of factors have been identified that can cause the development of leukemia. Modern medicine divides these reasons into four large groups. The first group includes infectious viral causes of leukemia. There are, of course, plenty of viruses in our world. By affecting the human body, some viruses contribute to the transformation of a normal cell into a cancer one.

As for the second group of reasons, it includes all hereditary factors. It has been scientifically proven that if at least one person in a family suffers from leukemia, this disease will definitely make itself felt in his children, grandchildren or great-grandchildren. Leukemia is quite common in families where one or two parents have hereditary chromosomal defects. Such defects include: Turner syndrome, Bloom syndrome, Down syndrome, Fanconi syndrome and some others. There are cases of the development of leukemia in hereditary diseases that are directly related to defects in the immune system.

The third group of causes for the development of leukemia includes the action of chemical and leukozogenic factors. In simpler terms, the causes of the development of leukemia can be cytostatics that are prescribed to the patient for the treatment of cancer, penicillin antibiotics, as well as cephalosporins. Remember, the use of all of the above medications should be limited. When it comes to impact chemical substances, then it could be detergents synthetic origin, linoleum, carpeting and so on and so forth.

And finally, the fourth group of causes of leukemia development is radiation exposure. Clinical studies have established that in any type of leukemia, direct involvement of radiation damage to chromosomes in tumor development is possible. This is explained by the fact that the cells that make up the tumor substrate actually suffer their own radiation damage.

Source tiensmed.ru

Signs

Signs of acute leukemia

Like any acute disease, acute leukemia begins suddenly. Temperature rises sharply, join bacterial infections, for example, sore throats. All this is accompanied by severe weakness, lack of appetite, nausea, vomiting, pain in the bones and joints. All hematopoietic organs enlarge: liver, spleen, lymph nodes. Increased bleeding, pinpoint hemorrhages and bruises on the body, nosebleeds, and sometimes internal bleeding appear. Patients melt before our eyes: body weight decreases, waxy pallor appears. A large number of blasts can be detected in the blood during this period. Acute leukemia without treatment very quickly leads to the death of the patient. But with timely and adequate treatment, recovery occurs in most cases.

Signs of chronic leukemia

Chronic leukemia begins and progresses slowly, sometimes being discovered by chance during examination for other diseases. First there is some fatigue, weakness, poor appetite, then gradually more characteristic signs of leukemia appear: frequent infections and bleeding. The size of the liver, spleen, and lymph nodes increases.

Periods of exacerbation are usually followed by periods of remission (temporary absence of signs of the disease). With chronic leukemia, patients live without treatment for several months or years. Chronic leukemia can develop into untreatable acute forms (blast crises).

Source womenhealthnet.ru

Classification

All leukemias, depending on their ability to grow and develop proliferating neoplastic cells, are divided into two main types - acute and chronic. In the first case, the development of cellular elements is practically absent, and a large volume of immature cells accumulates in the blood at the early stages of differentiation, which causes inhibition of all hematopoiesis (hematopoiesis). These signs occur in more than 80% of all cases.

Chronic leukemia produces a population of granulocytic cells that have already developed to a certain extent, gradually replacing normal blood cells. It should be clearly understood that acute leukemia is not capable of turning into chronic and vice versa.

During acute leukemia there are three stages. The first is initial, usually assessed retrospectively, since clinically it either does not manifest itself at all, or is accompanied by slight general weakness, exacerbation of pre-existing chronic diseases, or activation of a herpes viral or other infection. Blood counts may be normal or slightly increased/decreased.

The advanced stage of acute leukemia is characterized by pronounced objective symptoms and consists of periods of exacerbations and remissions, ending either with a complete cure or with a transition to the third, terminal phase, when there is complete inhibition of the hematopoietic system and chemotherapy no longer has any effect.

As for chronic leukemia, it may not have any initial phase at all. Even after diagnosis, it can drag on for years, having a relatively benign course. This is the monoclonal phase of chronic leukemia, associated with the presence of one clone of neoplastic cellular elements. The development of the next, polyclonal stage (blast crisis stage) is due to the emergence of secondary tumor clones. In this case, the process will already proceed quickly with the appearance of many blast forms; it is during this period that the majority (about 80%) of patients with chronic leukemia die.

Depending on the degree of differentiation tumor cells There are undifferentiated, blast and cytic leukemias. Based on ideas about hematopoiesis, that is, according to cytogenesis, acute leukemias are lymphoblastic, myeloblastic, monoblastic, myelomonoblastic, erythromyeloblastic, megakaryoblastic and undifferentiated, and chronic leukemias of myelocytic origin are divided into myeloblastic, neutrophilic, eosinophilic, basophilic, as well as myelosclerosis, erythrema Iu or true polycythemia and essential thrombocythemia. Chronic leukemias of lymphocytic origin include chronic lymphocytic leukemia and paraproteinemic leukemias ( multiple myeloma, primary Waldenström macroglobulinemia, Sézary's disease - cutaneous lymphomatosis, Franklin heavy alpha chain disease). Chronic monocytic leukemias include chronic monocytic leukemia, histiocytosis X (Langerhans cell histiocytosis) and chronic myelomonocytic leukemia.

Source rusmedserv.com

In children

Leukemia in children (leukemia) is a systemic hemoblastosis, accompanied by a violation of bone marrow hematopoiesis and the replacement of normal blood cells with immature blast cells of the leukocyte series. In pediatric oncohematology, the frequency of leukemia is 4-5 cases per 100 thousand children. According to statistics, acute leukemia is the most common cancer childhood (approximately 30%); Most often, blood cancer affects children aged 2-5 years. An urgent problem in pediatrics is the one observed in last years a trend towards an increase in the incidence of leukemia among children and a continuing high mortality rate.

Causes

Some aspects of the development of leukemia in children still remain unclear. At the present stage, the etiological influence of radiation, oncogenic viral strains, chemical factors, hereditary predisposition, endogenous disorders (hormonal, immune) on the incidence of leukemia in children. Secondary leukemia can develop in a child who has had a history of radiation or chemotherapy for another cancer.

Today, the mechanisms of development of leukemia in children are usually considered from the point of view of mutation theory and the clonal concept. A mutation in the DNA of a hematopoietic cell is accompanied by a failure of differentiation at the stage of an immature blast cell with subsequent proliferation. Thus, leukemia cells are nothing more than clones of a mutated cell, incapable of differentiation and maturation and suppressing normal hematopoietic germs. Once in the blood, blast cells spread throughout the body, promoting leukemic infiltration of tissues and organs. Metastatic penetration of blast cells through the blood-brain barrier leads to infiltration of the membranes and substance of the brain and the development of neuroleukemia.

It has been noted that children with Down syndrome develop leukemia 15 times more often than other children. There is an increased risk of developing leukemia and other tumors in children with Li-Fraumeni, Klinefelter, Wiskott-Aldrich, Bloom syndromes, Fanconi anemia, primary immunodeficiencies (X-linked agammaglobulinemia, Louis-Barre ataxia-telangiectasia, etc.), polycythemia, etc.

Source krasotaimedicina.ru

Diagnostics

Bone marrow puncture is the main research method for leukemia. It is used to confirm the diagnosis and identify (morphological, immunophenotypic, cytogenetic) the type of leukemia. Aspiration of bone marrow can be difficult due to its hypoplasia (suppression of hematopoiesis) and the increased content of fibrous structures in it.

Myelogram (quantitative characteristics of all cellular forms of bone marrow) for acute leukemia: an increase in the content of blast cells by more than 5% and up to total blastosis; the morphology of blasts varies depending on the type of leukemia; an increase in the number of intermediate forms of leukemia cells; lymphocytosis; the red germ of hematopoiesis is suppressed (with the exception of acute erythromyelosis); megakaryocytes are absent or their number is insignificant (with the exception of acute megakaryoblastic leukemia).

Cytochemical research is the main method for diagnosing forms of acute leukemia. It is carried out to identify enzymes specific to various blasts. Thus, in ALL, a positive CHIC reaction to glycogen and a negative reaction to lipids, peroxidase, and chloroacetate esterase are determined. In acute myeloblastic leukemia - a positive reaction to myeloperoxidase, lipids, chloroacetate esterase.

Immunophenotyping of blasts (carried out using an automated method on a flow cytometer or enzyme immunoassay method on glass using light microscopy). Immunophenotyping allows one to determine, using monoclonal AT, the presence or absence of blast cell differentiation clusters (CD markers). Its implementation is primarily necessary for an accurate diagnosis of ALL (see Table 21-7 and Fig. 21-36), as well as in cases of impossibility of differential diagnosis of acute, morphologically undifferentiated lymphoblastic and myeloblastic leukemia. This is a fundamental point, since the treatment of these forms is different.

Cytogenetic study of leukemia cells allows us to identify chromosomal abnormalities, clarify the diagnosis and prognosis.

Source medicalplanet.su

Treatment

First, the doctor must determine whether the patient's symptoms are due to leukemia, or whether they are caused by anemia or an infectious disease. If cells characteristic of leukemia are found in the blood and bone marrow, further tests are carried out to determine the type of leukemia and outline a treatment program.

Acute leukemia is diagnosed when multiple blood tests reveal an abnormally elevated number of white blood cells. To confirm this diagnosis, a bone marrow biopsy is performed.

To treat acute leukemia, chemotherapy is carried out using various combinations of antitumor drugs. The goal of treatment is to destroy tumor cells.

The dose of such drugs must be carefully selected so that tumor cells are destroyed and healthy cells of the body are not damaged. The first phase of treatment is induction therapy. During this period, the patient receives the most intensive treatment for 4-6 weeks. This stage of therapy usually causes remission of the disease, which, however, may only be temporary if therapy is not continued.

The second phase of treatment is consolidation therapy, the purpose of which is to destroy the pathological cells currently present in the body. The drugs that the patient receives in this phase are necessary to overcome possible resistance to therapy. Maintenance chemotherapy usually lasts 2-3 years.
Most patients remain in hospital during the first phase of treatment because there is a high risk of infection as well as severe bleeding. Because these drugs suppress the production of white blood cells, you may feel worse and may require frequent blood transfusions.

Bone marrow transplantation may be an important part of treatment. This is a complex procedure in which all the blood cells produced are first destroyed by radiation, and then new cells from a suitable donor are introduced into the bone marrow with healthy cells. To prevent the invasion of tumor cells from the bone marrow, it is possible to carry out radiation therapy.

Today, an increasing number of cases of acute leukemia can be successfully treated, the prognosis is significantly improved, especially in children; More and more patients are being cured. In 90% of cases or more, remission is achieved, half of the patients survive for 5 years or more.

Source health.mail.ru

Chemotherapy

Chemotherapy regimens and programs depend on the type of leukemia. A distinction is made between chemotherapy for acute lymphoblastic leukemia and chemotherapy for myeloblastic leukemia. One of the most important achievements in hematology in the last decade has been the discovery of the differentiating effect of retinoic acid derivatives on blast cells of acute promyeloblastic leukemia. The advent of the commercially available drug all-trans-retinoic acid (ATRA) radically changed the fate of patients with this form of myeloblastic leukemia: from the least favorable prognosis, it turned into the most curable.

Acute leukemia is a systemic malignant disease of the hematopoietic tissue of the bone marrow, the morphological substrate of which is blast cells (cells at an early stage of development, immature), which affect the bone marrow, displacing normal cellular elements and spreading not only to the hematopoietic organs, but also to other organs and systems, including the central nervous system.

In acute leukemia, a large number of blast cells accumulate in the blood, which leads to inhibition of normal hematopoiesis of all germs. Such signs are detected in the blood in more than 80% of cases.

Spread of leukemia beyond the bone marrow to other organs or the central nervous system can cause various symptoms, such as headache, weakness, seizures, vomiting, and disturbances in gait and vision.

Some patients may complain of bones and joints due to their damage by leukemia cells.

Leukemia can lead to an increase in the size of the liver and spleen. If the lymph nodes are affected, they may become enlarged.

Source lechimdoma.ucoz.ru

Prevention

To prevent leukemia, it is very important to regularly visit your doctor for examination and take all required laboratory tests. If signs of the disease are detected, it is important to immediately visit a doctor. Currently, there are no clear measures to prevent leukemia, but once remission is achieved, proper maintenance therapy becomes necessary to prevent relapses. Constant monitoring of the patient by pediatricians and oncohematologists is important. After completing treatment for leukemia, a person should not move to places with different climatic conditions or subject their body to any procedures related to physiotherapy. It is important for children who have had leukemia to do preventive vaccinations in accordance with a schedule specially developed by doctors.

Acute leukemia is an aggressive form of blood cancer. The prognosis for a patient’s recovery with this disease is influenced, first of all, by timely diagnosis and the correct course of treatment. We will talk about the symptoms, effective methods of diagnosis and treatment of leukemia.

Causes of leukemia development

Acute blood leukemia (leukemia) develops due to a mutation in the hematopoietic precursor cell of leukocytes, which rapidly proliferates. Tumor clones displace normal hematopoietic cells and the bone marrow is deprived of the ability to produce blood cells in the required volume. After the release of immature mutated cells into the bloodstream, they accumulate in the peripheral blood and cause leukemic infiltration of internal organs.

All atypical cells have the same cytochemical and morphological characteristics, which confirms their cancerous origin and status as clones of the same blast.

The exact causes of acute leukemia are not clear, but specialists who deal with diseases of the hematopoietic system (hematologists) have identified a number of risk factors. These include:

• hereditary predisposition (diagnosed cases of leukemia in close relatives);
• some chromosomal pathologies (Down syndrome, Klinefelter's disease, etc.);
• viral infections (there is a risk of an abnormal immune response to the infectious agent, mainly influenza);
• hematological diseases (myelodysplasia, some types of anemia);
• exposure to radiation and chemical carcinogens (benzene, toluene, arsenic compounds);
• cytostatic therapy for other types of cancer (lymphomas, multiple myelomas, lymphogranulomatosis).

In most cases of acute leukemia, there are several causes of cell mutation. For example, it is believed that the development of lymphoblastic leukemia in children is due to the effects of adverse environmental factors on the body of the mother and child, the immune response to viral infections and hereditary predisposition. In some types of disease associated with a mutation of the MLL gene, the pathological change in blasts is completed even before the birth of the child.

Classification of acute leukemias

The acute form of the disease is diagnosed in 97% of all clinical cases leukemia. Transition acute leukemia into a chronic form is impossible, therefore the division according to the course of the disease does not correspond to a similar classification in another field of medicine.

“Exacerbation” of chronic leukemia is possible with prolonged exposure to carcinogenic factors that provoked the development of the disease. In this case, against the background of chronic leukemia, symptoms of acute leukemia are observed.

Morphologically, leukemias are divided into lymphoblastic (arising from lymphocyte precursor cells) and non-lymphoblastic. The second group combines all other forms of the disease.

Lymphoblastic leukemias, in turn, are classified according to the type of lymphocytes that gave rise to the process. There are pre-pre-B-lymphoblastic, pre-B-lymphoblastic, B-lymphoblastic and T-lymphoblastic forms of the disease.

Acute leukemias of the non-lymphoblastic type are divided into myeloblastic (develop from pre-granulocytes), mono- and myelomonoblastic (characterized by abnormal proliferation of monoblasts), megakaryoblastic and erythroblastic (develop from platelet and erythrocyte precursor cells, respectively).

In addition to lymphoblastic and non-lymphoblastic leukemia, undifferentiated leukemia is distinguished. This form of the disease is very aggressive, because the division of tumor cells without certain morphological characteristics occurs more actively than at more mature stages of their development.

Acute leukemia in adults is usually of the non-lymphoblastic type. In most cases, they have a myeloblastic form of leukemia. At risk are mainly elderly patients and those who are constantly in contact with chemical carcinogens and ionizing radiation.

Acute lymphoblastic leukemia is typical for children. The peak incidence occurs between 2 and 5 years, with boys getting sick more often than girls. Leukemia can also be diagnosed in adolescents - a small spike in the graph of incidence versus age is observed around 10-13 years.

Accurate determination of the morphological characteristics of cells is important for selecting the correct treatment tactics. The degree of differentiation of tumor clones determines the aggressiveness of the cancer and affects the patient’s survival prognosis.

Stages of the disease

The course of leukemia is usually divided into five stages or stages:

• initial stage;
• expanded stage;
• complete or incomplete remission;
• relapse;
• terminal stage.

In a number of clinical cases, a latent (primary) period is also distinguished. This term refers to the time that passes from exposure to a carcinogenic factor to the appearance of the first symptoms of the disease. Depending on the morphological type of cells, it takes from several months to several decades. Clinical manifestations diseases are caused by inhibition of hematopoiesis.

On initial stage Leukemia has no clinical symptoms. Anemia is rare, but a change in the number of leukocytes in one direction or another and slight thrombocytopenia may be observed.

Based on these signs, it is impossible to unambiguously diagnose developing leukemia, but often, in the absence of other reasons for anemia, a hematologist can refer the patient for a puncture of bone marrow tissue. Analysis of hematopoietic tissue gives an unambiguous result: with a diagnosis of “acute leukemia”, a large number of blast (immature) cells are found in the hematopoietic tissue.

Despite the theoretical possibility of diagnosis at an earlier stage, most often acute leukemia is detected at an advanced (clinical) stage.

In some forms of acute leukemia, symptoms do not appear, but characteristic changes in blood composition are noticeable (decrease in the number of reticulocytes, erythrocytes, platelets, increase in ESR, presence of blasts and disappearance of eosinophils, basophils, mature and transitional forms leukocytes).

The state of remission characterizes the complete disappearance of clinical symptoms of the disease. With complete remission, the absence of blasts in the peripheral blood is complemented by a low number of blasts in the bone marrow tissue (no more than 5%), and with incomplete remission, the number of immature cells against the background of hematological improvement remains high.

Relapse of acute leukemia is possible not only in the hematopoietic system, but also outside it. Each subsequent clinical manifestation of leukemia is prognostically more dangerous for the patient.

On terminal stage disease, there is a final inhibition of blood cell production, resistance to antitumor therapy and the development of necrotic processes in the body.

Symptoms of acute leukemia

The symptoms of acute leukemia create a characteristic clinical picture, therefore, at an advanced stage of the disease, an unambiguous diagnosis is possible. There are several syndromes that can occur with this disease:

• anemic (associated with sharp drop number of red blood cells);
• hemorrhagic (caused by a decrease in the number of platelets by 4-5 times relative to the norm);
• intoxication;
• proliferative or hyperplastic (associated with the spread of clones of immature cells into the peripheral blood and internal organs);
• osteoarticular.

Symptoms of acute leukemia

Symptoms in adults and children are not fundamentally different. The manifestation of leukemia is most often similar to the manifestations viral diseases(fever, chills, sweating). This is due to the fact that the patient’s blood does not contain mature cells of the immune system that can destroy the infection.

Frequent ARVI, exacerbation of chronic infections and the appearance of new ones (pneumonia, pyelonephritis, herpes, etc.) against the background of anemia and bleeding of the mucous membrane are an early diagnostic sign of leukemia.

Diagnosis of the disease

Diagnosis of leukemia consists of three stages: monitoring changes in the patient’s blood composition, studying the ratio of hematopoietic cells and blasts in the blood and bone marrow tissue, as well as a general study of the body.

A general blood test for acute leukemia reveals changes such as:

• decrease in hemoglobin, the number of reticulocytes and erythrocytes by 2-3 times compared to the norm (the number of red blood cells can be up to 1.0-1.5 * 10 9 / ml with a norm of 3.6-5.0 * 10 9 / ml);
• thrombocytopenia (the number of platelets can drop by an order of magnitude or more - up to 20 * 10 9 / l when the norm is 180-320 * 10 9 / l);
• change total number leukocytes, fixation different sizes white blood cells;
• leukemic failure (a small number of mature and transitional leukocytes - neutrophils, eosinophils, basophils, monocytes, lymphocytes in the presence of blasts);
• increased ESR.

A dynamic study is necessary not only to exclude errors in diagnosis, but also to monitor the rate of displacement of normal hematopoietic cells by blasts.

Despite the fact that leukemia has a number of characteristic clinical signs, the main method of diagnosing the disease is the study of a fragment of bone marrow, which is obtained by puncture of the sternum or trephine biopsy ilium. Cytochemical analysis (staining a smear with reagents) allows you to differentiate cells, and clarifying immunophenotyping allows you to finally establish the type of tumor clone.

In acute leukemia, the proportion of blasts usually exceeds 20%, the red germ of hematopoiesis is suppressed (the exception is cases of erythroblastic leukemia), megakaryocytes are absent or significantly reduced (the exception is megakaryoblastic leukemia). The number of lymphocytes in the hematopoietic tissue in leukemia is usually increased.

With vague symptoms and at the initial stage of the disease, there is a need for differential diagnosis, which is aimed at excluding mononucleosis, thrombocytopenic purpura, HIV infection, leukemoid reactions to severe systemic infections, etc. The results of a myelogram make it possible to unambiguously determine the disease.

General diagnostics with ECG, ultrasound, x-ray of internal organs, as well as spinal puncture are carried out to determine the degree of damage to the body by blast infiltration.

Treatment of acute leukemia

Treatment of acute leukemia can be done in several ways, depending on the stage of the disease, the degree of damage to internal organs and the patient’s health condition. There are two main methods of treatment for leukemia:

• chemotherapy with several cytostatics;
• bone marrow transplantation (BMT).

Additionally, in the presence of foci of disease outside the bone marrow, irradiation of the affected organ (including the brain in neuroleukemia) and endolumbar administration of cytostatic solutions are performed.

When diagnosed with acute leukemia, treatment is aimed at destroying blasts, i.e. in fact, the patient’s body is left without the ability to protect against infectious agents and with an abnormally low number of red blood cells and platelets. To a large extent, the patient’s survival depends on maintaining sterile conditions and timely administration of antibiotics.

To compensate for anemia and thrombocytopenia, the patient is given a transfusion of blood components. Complementary therapy is also aimed at reducing intoxication of the body.

Most effective method treatment of acute leukemia is considered TCM. Transplantation of healthy stem cells helps restore normal hematopoiesis to the patient. However, due to difficulties in finding donors and many contraindications to surgery, bone marrow transplantation is possible in a very small proportion of cases.

BMT is performed only upon complete remission (usually the first) and after intensive immunosuppressive therapy. Engraftment of allogeneic bone marrow guarantees a sharp reduction in the chances of relapse.

Acute leukemia is a serious and aggressive disease. However modern methods treatments can virtually guarantee the patient's survival for at least several years after the end of therapy. Timely diagnosis and careful patient care play an important role in the success of treatment.

Leukemia is a systemic blood disease characterized by a return to metaplasia and hyperplasia of hematopoiesis with a sharp delay in cell differentiation. Based on the severity of their course, leukemia is divided into acute and chronic. The latter differ in the predominant damage to the hematopoietic germ. Typical changes are detected in the leukocyte formula (the appearance of young cells of the myeloid or lymphocytic series).

There are acute lymphoblastic and myeloblastic leukemias.

Acute lymphoblastic and myeloblastic leukemia can develop during the transformation of chronic myeloid leukemia or secondary to a previous myodysplastic syndrome, and also arise de novo.

In acute leukemia, insufficient cell maturation occurs. Proliferation of cells incapable of maturation leads to the accumulation of non-functioning cells, which progressively fill the bone marrow space, displacing normal elements of hematopoiesis. Eventually this proliferation breaks out into the blood. In adults, acute myeloid leukemia is reported approximately four times more often than acute lymphoblastic leukemia. In children, the ratio is opposite; lymphoblastic leukemia is more typical for them. Clinical manifestations are usually related to bone marrow failure (anemia, bleeding, or infection).

Symptoms and signs of acute leukemia

The main manifestation of acute leukemia is pancytopenia. Patients may feel pale, tired, or have rapid breathing. Thrombocytopenia can lead to bleeding, and neutropenia can lead to infection. Often the symptoms are mild and difficult to separate from general complaints such as fatigue and signs of prolonged viral infection. The situation is clarified by a clinical blood test.

The clinical picture is characterized by an acute, violent onset, often with septic manifestations (high temperature). The liver, spleen and lymph nodes are not enlarged. In most cases, there are bruises and bruises on the body.

In peripheral blood - anemia, often leukopenia.

BM transplantation is actively used.

Chronic myeloid leukemia is characterized by a calm course in the first stage of the disease. Unreasonable weakness and bruises on the body are observed. Then abdominal pain appears. Upon examination, enlarged (moderate) lymph nodes are detected in different locations.

When examining peripheral blood - anemia, leukocytosis, leukocyte formula.

Chronic lymphocytic leukemia belongs to a large group of lymphoproliferative diseases. In its classical form, this disease is characterized by a sharp proliferation of B- and, less commonly, T-lymphocytes.

The patient develops progressive weakness, all lymph nodes begin to enlarge, which is noted by the patient himself. On objective examination, all lymph nodes are enlarged, medium density, smooth. The spleen is sharply enlarged, the organ is dense and painless. Occasionally, due to inflammatory processes, perisplenitis may develop, which is manifested by a friction noise over the spleen area.

A blood test revealed leukocytosis, later normocytic anemia. The leukocyte formula contains a large number (up to 90%) of lymphocytes. The same picture is revealed in the bone marrow punctate.

In the acquired variant, the autoimmune genesis of the disease associated with taking medications is identified.

Acute lymphoblastic leukemia

• Usually B-cell, sometimes T-cell.
• Mostly children and young people are affected.

ALL can be pre-B- or T-cell type (Chapter 4 discusses the physiology of lymphoid tissue). In both cases, immature lymphoblasts are produced. There are 2 classifications of ALL: morphological (FAB) and immunological. The FAB classification is not widely used and does not reflect the immunological nature of the ALL subtypes, which is very important. Let's give an example. It is known that morphologically, lymphoblastic cells of the L3 variant are often detected in a disease similar to ALL, such as non-Hodgkin lymphoma of small non-split cells, or Burkitt lymphoma. However, the treatment of the latter differs from the treatment of ALL. Immunological classification is very useful for differentiating these diseases.

Acute myeloblastic leukemia

There are 7 types (M1-M7).

Mostly adults, including the elderly, are affected.

Poor prognostic factors:

• Age (prognosis worsens with age).
• High leukocytosis at the time of patient's admission.
• Preexisting myelodysplastic syndrome.
• Acute leukemia with detection of the Philadelphia chromosome.
• The prognosis is determined by the type of leukemia, determined on the basis of morphology, chromosomal abnormalities and cell surface markers.

Damage to the erythrocyte germ.

Anemia. It occurs as a result of inhibition of erythropoiesis by leukemic cells, as well as as a result of bleeding against the background of thrombocytopenia and coagulation disorders. The average cell volume is usually normal or increased unless blood loss predominates. Damage to the leukocyte lineage.

Pneumonia caused by leukemia: fever, malaise, pain in muscles and joints.

Neutropenia: occurs secondarily as a consequence of infiltration of the bone marrow (hereinafter referred to as BM) by leukemic cells.

Because the term myeloid is sometimes used to designate only the neutrophilic lineage, in the past this group of leukemias was called acute nonlymphocytic leukemias, but the term acute myeloid leukemia is now preferred. Subtypes M1, M2 and M3 represent different stages of myeloblast differentiation. M0 AML can be identified by the myeloid nature of cell surface markers, such as CD33, but blasts in this disease do not produce myeloid enzymes, which is why histochemical staining for myeloperoxidase is negative. In the M1-MZ subtypes, the degree of primary granulation gradually increases so that the M3 subtype represents acute promyelocytic leukemia. M4-M5 AML are monoblastic leukemias with or without myeloid elements, respectively. M6 AML is erythroleukemia, and M7 is megakaryoblastic leukemia. AML subtypes differ in morphology, histochemical staining, karyotype, and immunophenotype of pathological cells. The listed methods also help to distinguish AML from ALL with ambiguous cell morphology.

Because of the need for cells to self-replicate and reproduce throughout a person's life, blasts are not programmed to die. Mature descendants (erythrocytes, neutrophils, platelets) have a finite life span, and their death is predetermined.

In most cases, the cause of AML is unknown, but a number of etiological factors have been identified. Radiation is a weak but reliable leukosogen. Leukemia is also caused by some chemotherapeutic agents. In addition, AML can develop as a consequence of previous hematological disorders.

Damage to the platelet lineage

Thrombocytopenia develops as a result of inhibition of the myeloid lineage of hematopoiesis against the background of leukemic infiltration of BM. The functional usefulness of the resulting platelets is impaired. The risk of bleeding increases when the platelet count decreases below 10x109/l, and with concomitant sepsis and coagulopathy - below 20x109/l.

Changes in blood clotting

Vary from prolongation of prothrombin time to disseminated intravascular coagulation syndrome: may be a consequence of sepsis or leukemia itself, especially in acute promyelocytic leukemia (M3).

Diagnostics

Diagnosis of AML or ALL requires identification of leukemic blasts. Even when blasts are found in the peripheral blood, a bone marrow examination is always performed to confirm leukemic infiltration. The presence of more than 30% blasts is the standard criterion for diagnosing AML (as opposed to myelodysplastic syndromes, discussed below).

Often blasts can be identified as belonging to the myeloid or lymphoid series according to their morphological characteristics. Myeloblasts are larger than lymphoblasts, have very thin strands of nuclear chromatin and large prominent nucleoli. Lymphoblasts are smaller in size, with less cytoplasm and less prominent nucleoli. Often the patient’s blasts cannot be clearly attributed to the myeloid or lymphoid lineage and require further research. Myeloid blasts of type M1-M4 are stained in the test for myeloperoxidase, and blasts of type M4-M5 are stained for nonspecific esterase. Some M6 blasts exhibit a PAS response, and some M7 blasts exhibit a response to factor VIII antigen. Blasts in ALL do not stain for myeloperoxidase or nonspecific esterase, but sometimes they contain large PAS-positive granules. When immunophenotyping, belonging to myeloid blasts is established by the presence of CD33 and other myeloid antigens, and to lymphoid blasts - by CD 19 and CD10 (CALLA). IN difficult cases At the final stages of examining the patient, a cytogenetic study should be performed to make a final diagnosis. Obtaining cytogenetic data often requires considerable time.

Diagnosis confirmation

They collect a complete history of the disease and try to find out the etiological factors. The duration of the disease is determined (whether its development was preceded by a chronic condition, for example myelodysplasia), previous diseases (Down syndrome, radiation or chemotherapy). They find out the patient’s occupation (possibility of radiation exposure, contact with benzene and other factors that cause mutations), family history (rare hereditary diseases, such as Fanconi anemia).

The patient is examined to identify additional information to establish a diagnosis (lymphadenopathy, hepatosplenomegaly, gingival hyperplasia) and to detect possible sources of infection (caries, skin lesions, etc.).

The final confirmation of the diagnosis is based on the results of a bone marrow puncture. The obtained material should be sent for morphological examination, chromosomal analysis and identification of surface cellular markers.

Research

Blood tests usually reveal anemia with normal or elevated MCV. The number of leukocytes can be different: from low - 1x109/l to high - 500x109/l and higher. Most often, patients are diagnosed with leukocytosis below 100x109/l. Severe thrombocytopenia is typical, but its magnitude is variable. The usual diagnosis is the detection of blast cells in a blood smear.

Bone marrow analysis is the most valuable diagnostic method, and at the same time it makes it possible to obtain material for cytological, cytogenetic and immunological phenotyping. If bone marrow cannot be obtained, a trephine biopsy is necessary. The bone marrow is usually hypercellular with replacement of normal elements by leukemic blast cells in varying degrees(but more than 20%). The presence of Auer rods in the cytoplasm of blast cells indicates the myeloblastic type of leukemia.

Priority areas of therapy

• Stabilize the patient's condition.
• Treatment begins emergency conditions, such as bleeding or sepsis.
• Confirm the diagnosis.
• Determine the treatment strategy.

Acute leukemia: treatment

• Stabilization of the patient's condition.
• Airways. Stridor occurs with obstruction of the upper respiratory tract at the level of the mediastinum in certain types of leukemia, especially T-lymphoblastic. If stridor is detected, immediately call an anesthesiologist and transport the patient to the department intensive care.
• Breath. Shortness of breath may be a consequence of infection (including atypical), leukostasis (high white blood cell count), severe anemia, heart failure (leukostasis, severe sepsis), pulmonary hemorrhage. Oxygen therapy is started: if possible, oxygen saturation is monitored using a pulse oximeter and do not resort to arterial puncture to study blood gases if the patient has thrombocytopenia.
• Circulation. Typically, shock in patients with leukemia occurs due to sepsis, but blood loss should be excluded if the patient has thrombocytopenia and coagulopathy, as well as heart failure due to leukostasis.
• Replenish the bcc.
• If sepsis is suspected, broad-spectrum antibiotics are immediately administered (after blood is taken for culture).
• Seek advice from a hematologist.

In recent years, the prognosis for acute leukemia has improved and has become dependent on an accurate diagnosis. Currently, about 80% of children with acute lymphoblastic leukemia are cured, while among adults the recovery rate for acute myeloid leukemia does not exceed 30%. The diagnosis of leukemia is extremely stressful for young patients and their families, and the doctor must spend a lot of time discussing the questions and problems that arise in this regard. Before starting chemotherapy, you need to know the following points.

Sperm preservation

Almost all types of chemotherapy lead to infertility with a high frequency. If the patient wishes, before starting chemotherapy, everything possible should be done to preserve sperm and its subsequent storage. Unfortunately, in practice, with leukemia, sperm becomes non-viable, and the need for rapid initiation of chemotherapy makes subsequent collection and storage of sperm useless.

Discussion of side effects

The patient should be warned about hair loss, infertility, vomiting (with the use of antiemetic drugs, vomiting may be less pronounced, although its occurrence is determined individual characteristics), infectious complications, bleeding, inflammation of the mucous membranes, etc. It may be helpful to provide patient-centered literature on acute leukemia and its chemotherapy.

Other provisions requiring discussion

Carrying out a spinal puncture to exclude damage to the central nervous system by the pathological process is indicated for:

• acute lymphoblastic leukemia;
• acute myeloblastic leukemia;
• the presence of neurological symptoms in a patient with leukemia.

Due to possible occurrence In the future, the need for BM transplantation requires HLA typing. However, this study is usually performed at a later stage after clinical remission has been achieved.

It is necessary to determine whether the patient is infected with CMV, and in the future, when treating CMV-negative patients, use only CMV-negative drugs, especially if BM transplantation is planned.

Before starting chemotherapy

Allopurinol is prescribed 24 hours before the start of chemotherapy. If the risk of tumor lysis syndrome is high, rasburicase is prescribed.

Prescribe regular (4-5 times a day) antiseptic treatment of the oral cavity in combination with antifungal drugs (nystatin suspension, amphotericin tablets, fluconazole for oral administration).

The patient is adequately hydrated, providing him with 3 l/day of fluid.

Before starting chemotherapy, antiemetic drugs are prescribed; the patient must take them regularly throughout the course of chemotherapy:

• ondansetron 4-8 mg intravenously or orally 2 times a day;
• metoclopramide intravenously or orally with dexamethasone.

Therapy for acute myeloid leukemia

If left untreated, patients with AML quickly die due to uncontrolled infection or bleeding. Basic treatment consists of intensive chemotherapy, leading to bone marrow hypoplasia and the release not only of intact blasts, but also of normal cells, which should ensure the restoration of normal hematopoietic sprouts. Often used regimens include a combination of anthracyclines (daunorubicin or idarubicin) and Ara-C (cytarabine). With this treatment, in approximately 65% ​​of patients the disease goes into remission, and more often in young people. A distinction should be made between remission and recovery. Remission merely reflects the absence of visible leukemic blasts; and if treatment is stopped after its induction, a small number of patients will remain in remission and actually be cured. Post-remission intensive therapy increases the duration of remission and the cure rate. However, even with intensive consolidation therapy (amplification therapy), only 30-40% of patients are cured using standard chemotherapy.

Acute promyelocytic leukemia. It has been shown that oral administration of the trans-isomer of retinoic acid can stimulate the differentiation of APML cells and lead to complete histological and cytogenetic remission. Unfortunately, remission is not long-term; in addition, standard chemotherapy is necessary. However, establishing that treatment< ATRA вызывает дифференцировку и подавление злокачественного клона, стало ключевым компонентом modern therapy of this disease.

Treatment of acute lymphoblastic leukemia

For adult patients with ALL, therapeutic regimens used in children are ineffective: much more intensive treatment is required; and even then, only 35-50% of patients are cured with standard chemotherapy. The most encouraging data were obtained in patients under 30 years of age; in patients over 60 years of age, survival rates were significantly reduced. As previously emphasized, patients with true B-cell ALL (L3) are treated according to protocols for the treatment of small non-Hodgkin's lymphomas of small non-split cells (Burkitt's lymphoma). Patients with ALL with the Philadelphia chromosome have an extremely poor prognosis and, if a compatible donor is available, should undergo BMT during first remission.

Treatment of emergency conditions

• Infection. Until the results of a complete blood count are obtained, the patient should be considered neutropenic and aggressive treatment for the infection should be initiated.
• Bleeding.
• Transfusion of compatible blood (if possible free of CMV) is carried out. Take precautions when the leukocyte count is high.
• If the platelet count is below 20x109/L, one dose of platelet concentrate is prescribed. Its administration is also indicated when bleeding occurs in patients with a platelet count below 50x109.
• When the prothrombin time is prolonged (more than 1.5 times compared to the control value), 4-5 doses of fresh frozen plasma are administered.
• If fibrinogen levels decrease, additional cryoprecipitate may be required.
• Transfusions with hyperleukocytosis are dangerous and can provoke complications of leukemia.
• Hyperleukocytosis. Discuss treatment tactics with a hematologist. Urgent leukapheresis may be required, preferably in an intensive care unit.

The first question is whether specific treatment is necessary. It is quite aggressive, has many side effects and may not be suitable for elderly patients or patients with other serious illnesses. Such patients can only be offered supportive therapy, which can significantly improve the patient's condition.

Specific therapy

Treatment of acute leukemia: specific therapy

• Detection and treatment infectious diseases(infections urinary tract, oral candidiasis, infections of teeth, gums and skin).
• Correction of anemia with red blood cell infusions.
• Stopping thrombocytopenic bleeding using platelet transfusion.
• If possible, install a central venous catheter for chemotherapy.
• Carefully inform the patient and obtain his consent.

If a decision is made to begin specific therapy, the patient should be prepared for it in accordance with the measures. It is unwise to undertake aggressive treatment of acute leukemia unless adequate supportive care is provided. The goal of treatment is to destroy the leukemic clone without damaging the remaining stem cells from which hematopoietic tissue will be restored. Treatment consists of three phases.

• Induction of remission. In this phase, combination chemotherapy destroys the tumor. The patient goes through a period of severe bone marrow hypoplasia, requiring intensive care and support in a hospital setting with specially trained medical personnel.
• Consolidation of remission. If remission has been achieved through induction therapy, the residual effects of the disease are suppressed in the consolidation phase. It consists of several courses of chemotherapy, which again cause bone marrow hypoplasia. For leukemia with a poor prognosis, stem cell transplantation is possible.
• Maintaining remission. If, with lymphoblastic leukemia, the patient remains in remission after the consolidation phase, they begin maintenance therapy, consisting of repeated courses of drug treatment. This can last for 3 years in the absence of exacerbation and is usually outpatient. Then specific therapy is stopped and the patient is observed. (It is believed that the maintenance phase is not needed for patients with acute myeloid leukemia who have achieved complete remission after the induction and consolidation phases.)

Treatment of ALL should be aimed at preventing damage to the central nervous system, since this is a special zone where conventional drugs do not penetrate. It consists of a combination of radiation to the head, intrathecal chemotherapy and high doses of methotrexate, which crosses the blood-brain barrier.

Detailed descriptions of treatment regimens can be found in special manuals. If the first induction course does not lead to remission, an alternative combination of drugs can be resorted to, but if there is no remission on the second attempt, a poor prognosis is obvious. If a relapse occurs during or soon after treatment, the prognosis is poor and treatment is difficult. The longer the remission lasts and no exacerbation occurs, the greater the chance of further treatment being effective.

Maintenance treatment

Intensive and potentially curative therapy is exacerbated by periods of severe bone marrow suppression and is impossible without adequate and skilled supportive care. The following problems usually occur.

Anemia. Anemia is treated with red blood cell infusion to maintain hemoglobin levels >100 g/L.

Bleeding. For recurrent thrombocytopenic bleeding, platelet infusion is necessary. Prophylactic platelet infusion is necessary to maintain platelet count >10x109/L. Emerging coagulation disorders require accurate diagnosis and, if appropriate treatment is necessary, fresh frozen plasma is usually used.

Infection. Fever (>38°C) lasting >1 hour in a patient with neutropenia indicates possible sepsis. Parenteral treatment with broad-spectrum antibiotics is important. Empirically, a combination of aminoglycosides (eg, gentamicin) with broad-spectrum penicillins (eg, piperacillin/tazobactam) is used. This combination is synergistic in its mechanism of bactericidal action, and treatment can be continued for at least 3 days after the fever has resolved. The microorganisms most often associated with severe neutropenia are the gram-positive bacteria St. aureus and St. epidermidis, which are present on the skin and penetrate into the human body through intravenous catheters and transfusion systems. Gram-negative microbes most often originate from the gastrointestinal tract and are activated in chemotherapy-induced mucositis. Escherichia coli, Pseudomonas and Klebsiella are more likely to lead to rapid deterioration of the patient's condition and require immediate empirical treatment. Gram-positive infections require treatment with vancomycin.

Patients with acute lymphocytic leukemia are susceptible to infection with Pneumocystis carinii, which causes severe pneumonia. Prophylaxis with cotrimoxazole is carried out during chemotherapy. Diagnosis can be difficult and may require either bronchoalveolar lavage or open lung biopsy. Treatment is carried out with high doses of cotrimoxazole, first intravenously, followed by switching to oral administration at the first opportunity.

Oral and pharyngeal candidiasis are common. If local infection is detected, fluconazole is effective. During intensive chemotherapy, systemic mycoses are usually prevented with fluconazole or itraconazole.

For systemic fungal infections of Candida and aspergillosis, intravenous amphotericin-B is required for at least 3 weeks, but the drug is nephro- and hepatotoxic. In this regard, the state of kidney and liver function is monitored, especially if the patient receives an antibiotic with the same nephrotoxic effect. As a rule, it is necessary to administer additional potassium. For patients who have experienced nephrotoxicity when treated with standard amphotericin-B, or those who require high doses of the drug to treat aspergillosis, a lipid form of amphotericin can be recommended without the risk of kidney damage. New ones have now been added to treat fungal infections. antifungal drugs caspofungin and voriconazole.

Herpes simplex on the face around the lips and nose often occurs during ablative treatment of acute leukemia and is treated with acyclovir. If the patient has a history of herpetic rashes, or the titers of antibodies to herpes simplex are increased, the drug can be prescribed prophylactically. Herpes zoster manifests itself as chicken pox or, if reactivated, herpes zoster. It must be treated immediately with high doses of acyclovir, as it can be fatal in immunocompromised individuals.

The value of isolated equipment and services, such as laminar airflow rooms, is debated, but may help build awareness of the need for a strong barrier in nursing practice. This isolation is often psychologically stressful for the patient.

Metabolic problems. Along with constant monitoring of kidney and liver function and homeostasis indicators, it is necessary to monitor the fluid balance in the body. Patients often suffer from severe anorexia as a side effect of treatment; Due to difficulties with fluid intake, intravenous administration of fluids and electrolytes is necessary. As a result of the use of antibiotics (eg aminoglycosides) and antifungal agents(amphotericin) toxic kidney damage occurs. Cell destruction during the period of induction of remission sharply increases production uric acid, which can lead to kidney failure. By monitoring biochemical parameters, allopurinol is used and solutions are administered intravenously to prevent these complications. Sometimes hemodialysis may be necessary.

Psychological support. It forms a key aspect of treatment. The patient should be fully informed, all questions should be answered and, as far as possible, his fears should be dealt with. The optimistic attitude of doctors is vitally needed. During periods of severe bone marrow failure and septic episodes, mania, hallucinations and paranoia are common and must be met with patience and understanding.

Alternative therapy. Mild chemotherapy, not designed to achieve remission, can be used to control excess tumor proliferation. The drugs used for this are hydroxyurea and mercaptopurine. The goal is to reduce the number of white blood cells without developing bone marrow failure.

Bone marrow and peripheral blood stem cell transplantation

Traditionally, only blood and bone marrow transplantation (BMT) offer hope of a “cure” for various hematological diseases. With the progress of treatment standards, indications for TCM are becoming more precise. The type of transplantation is determined depending on the donor and source of stem cells. In allogeneic BMT, stem cells are taken either from a relative (usually an HLA-matched sibling) or from an unrelated volunteer donor carefully matched by HLA. During autotransplantation, stem cells are taken from the patient and stored until the desired moment in the gas phase of liquid nitrogen. Stem cells can be taken from either bone marrow or blood.

Self-transplantation of bone marrow

General indications for bone marrow allotransplantation

• Neoplasia caused by totipotent or pluripotent stem cells (eg, leukemia).
• Diseases accompanied by insufficiency of hematopoiesis (for example, aplastic anemia).
• Severe hereditary defects in blood cell production (for example, thalassemia, immunodeficiencies).
• Inborn errors of metabolism with loss of enzymes or cell lines

Healthy stem cells from the donor's bone marrow or blood are injected intravenously into the blood of a suitably "prepared" recipient. Preparatory treatment (chemotherapy with radiation treatment or without it) destroys malignant cells and suppresses the recipient’s immunity as well as it destroys its hematopoietic tissue. The injected donor cells “settle” in the bone marrow, take root and produce a sufficient number of red blood cells, granulocytes, and platelets that the patient needs over the next approximately 3-4 weeks. During the aplasia period, there is a risk of infection and bleeding, and intensive supportive care as described above is necessary. It takes several years to restore normal immunity, and the patient remains at risk of possible infections, especially in the first year. The advantage of receiving donor stem cells is that the donor's immune system can recognize the recipient's remaining malignant cells and destroy them. The immunological graft-versus-disease effect is a powerful tool against many hematological tumors. In post-plantation relapse, it can be enhanced by an infusion of donor T cells, called donor lymphocyte infusion.

Patients tolerate BMT with difficulty, and the operation is accompanied by high mortality. The best results are obtained in patients with minimal remnants of the disease and in persons under the age of 20 years who have an HLA-identical relative donor. Older patients also undergo transplantation, but the results get progressively worse with age, and the upper limit for its use is 55 years. The risks and outcomes of transplantation depend on several factors that are related to both the patient and the disease. A total of 25% of patients die from transplantation-related complications, such as graft-versus-host conflict, and the rest from a significant risk of disease relapse. The long-term survival rate of patients with acute leukemia who underwent BMT is about 50%.

Complications of bone marrow allotransplantation

• Mucositis.
• Chronic graft-versus-host conflict.
• Infections.
• Bleeding
• Infertility.
• Education against the master."
• Acute conflict “transplant cataracts.
• Pneumonitis.
• Secondary malignant diseases

Graft-versus-host disease

The graft-versus-host conflict arises due to the cytotoxic activity of donor T-lymphocytes, which are sensitized to the new host, perceiving it as a foreign object. There are acute and chronic forms of conflict.

Acute form. In approximately one third of patients, the graft-versus-host conflict develops in the first 100 days after transplantation. It can affect the skin with rashes, the liver with jaundice, and the intestines with diarrhea, and ranges in severity from moderate to fatal. Prevention - selection of a donor according to the HLA system, immunosuppressants, including methotrexate and cyclosporine, as well as antithymocyte globulin. More severe forms difficult to treat and, despite high doses of corticosteroids, can lead to death.

Chronic form. It follows the acute form or occurs independently and later than the acute form. It often resembles a connective tissue disease, although in mild cases it only appears as a rash. Chronic graft-versus-host conflict is usually treated with corticosteroids and long-term immunosuppression, such as cyclosporine. WITH chronic form a graft-versus-leukemia effect may be combined to reduce the incidence of disease relapse.

Infection

Infections are another major problem encountered during the recovery period after BMT.

Reduced intensity bone marrow transplantation

The concept of reduced-intensity BMT developed as an attempt to reduce the mortality of allotransplantation. Instead of intensive preparation that worsens the patient's condition due to organ damage, relatively low doses of drugs such as fludarabine and cyclophosphamide are used to immunosuppress the patient, which allows the donor cells to engraft. The emerging donor immune system then eliminates malignant cells through a graft-versus-disease effect, which after transplantation can be enhanced by the selective use of donor T-lymphocyte infusions. This type of transplantation is less toxic and allows BMT to be performed in older patients. However, relapses and post-transplant infections continue to be a concern; the role of this type of transplantation is still under study.

Autologous bone marrow transplantation

In this procedure, the patient's own stem cells are first obtained and frozen. After preparatory treatment, autologous stem cells are reinfused to rescue the patient's bone marrow damage and aplasia caused by chemotherapy. Autologous bone marrow transplantation can be used for diseases that do not primarily affect hematopoietic tissue, or in patients who have achieved very good remission. The preferred source of stem cells for autotransplantation is peripheral blood. These stem cells engraft faster; Bone marrow recovery occurs within 2-3 weeks. In this case, the risk of graft-versus-host conflict is eliminated and immunosuppression is not required. Autologous stem cell transplantation compared to allogeneic BMT provides lower mortality - about 5%, but the relapse rate is higher. Whether stem cells require special treatment (“purification”) to remove remaining leukemia cells is debated.

Prognosis for acute leukemia

Without treatment, the average life expectancy of patients with acute leukemia is about 5 weeks. It can be extended to several months with maintenance treatment. Patients who have specific treatment achieve remission and have a better outcome. Approximately 80% of adult patients with ALL or AML under the age of 60 years achieve remission. Remission rates are lower in older patients. The number of relapses remains high.

National and international research has led to sustained improvements in leukemia survival. Achievements have been achieved with the introduction of drugs such as ATRA (all-trans retinoic acid) for acute promyelocytic leukemia, which is expressed by a sharp decrease in the number of deaths from bleeding in this leukemia. The goal of ongoing trials is to improve survival, especially in diseases with common or high risk, as well as determining the location of transplantation.

Leukemia (leukemia) is a malignant disease of white blood cells. The disease begins in the bone marrow and then spreads to the blood, lymph nodes, spleen, liver, central nervous system (CNS), and other organs. Leukemia can occur in both children and adults.

Leukemia is complex disease and has a lot various types and subtypes. Treatment and outcome vary widely depending on the type of leukemia and other individual factors.

Circulatory and lymphatic systems

To understand the different types of leukemia, it is helpful to have basic information about the circulatory and lymphatic systems.

Bone marrow is the soft, spongy, inner part of bones. All blood cells are produced in the bone marrow. In infants, bone marrow is found in almost all the bones of the body. By adolescence, bone marrow is stored mainly in the flat bones of the skull, shoulder blades, ribs, and pelvis.

Bone marrow contains blood-forming cells, fat cells, and tissues that help blood cells grow. Early (primitive) blood cells are called stem cells. These stem cells grow (mature) in a specific order and produce red blood cells (erythrocytes), white blood cells (white blood cells) and platelets.

Red blood cells carry oxygen from the lungs to other tissues of the body. They also remove carbon dioxide, a waste product of cellular activity. A decrease in the number of red blood cells (anemia, anemia) causes weakness, shortness of breath and increased fatigue.

Blood leukocytes help protect the body from germs, bacteria and viruses. There are three main types of leukocytes: granulocytes, monocytes and lymphocytes. Each type plays a special role in protecting the body against infection.

Platelets prevent bleeding from cuts and bruises.

The lymphatic system consists of lymphatic vessels, lymph nodes and lymph.

Lymphatic vessels resemble veins, but they do not carry blood, but a clear liquid - lymph. Lymph consists of excess tissue fluid, waste products and immune system cells

The lymph nodes(sometimes called lymph glands) are bean-shaped organs located along the lymphatic vessels. Lymph nodes contain cells of the immune system. They can increase in size more often during inflammation, especially in children, but sometimes their increase can be a sign of leukemia, when the tumor process has spread beyond the bone marrow.

How common is acute leukemia in adults?

In 2002, 8149 cases of leukemia were identified in Russia. Of these, acute leukemia accounted for 3257 cases, and subacute and chronic leukemia - 4872 cases.

It is estimated that 33,440 new cases of leukemia will be diagnosed in the United States in 2004. Approximately half of the cases will be acute leukemia. The most common type of acute leukemia in adults is acute myeloid leukemia(AML). At the same time, 11,920 new cases of AML are expected to be identified.

During 2004, 8,870 patients may die from acute leukemia in the United States.

The average age of patients with acute myeloid leukemia (AML) is 65 years. This is a disease of older people. The chance of developing leukemia for a 50-year-old person is 1 in 50,000, and for a 70-year-old it is 1 in 7,000. AML occurs more often in men compared to women.

Acute lymphoblastic leukemia (ALL) is more often diagnosed in children than in adults, and is most common before the age of 10 years. The likelihood of being diagnosed with ALL in a 50-year-old person is 1 in 125,000, and for a 70-year-old it is 1 in 60,000.

African Americans are 2 times less likely to develop ALL than the white population of America. Their risk of developing AML is also slightly lower than that of the white population.

With AML and ALL in adults, long-term remission or recovery can be achieved in 20-30% of cases. Depending on certain features of leukemia cells, the prognosis (outcome) of patients with AML and ALL may be better or worse.

What causes acute leukemia and can it be prevented?

A risk factor is something that increases the likelihood of disease. Some risk factors, such as smoking, can be eliminated. Other factors, such as age, cannot be changed.

Smoking is a proven risk factor for acute myeloid leukemia (AML). Although many people know that smoking causes lung cancer, few realize that smoking can affect cells not directly exposed to smoke.

Cancer-causing substances found in tobacco smoke enter the bloodstream and spread throughout the body. One fifth of AML cases are caused by smoking. People who smoke should try to quit smoking.

There are some factors environment which are associated with the development of acute leukemia. For example, prolonged contact with gasoline is a risk factor for AML, and exposure to high doses of radiation (explosion atomic bomb or nuclear reactor incident) increases the risk of AML and acute lymphoblastic leukemia (ALL).

People who have had other cancers and were treated with certain anticancer drugs are at increased risk of developing AML. Most of these cases of AML occur within 9 years after treatment for Hodgkin's disease (lymphogranulomatosis), non-Hodgkin's lymphoma (lymphosarcoma), ALL, or other malignant tumors, for example, breast and ovarian cancer.

There is some concern regarding high voltage transmission lines as a risk factor for leukemia. According to some data, in these situations the risk of leukemia is not increased or increased slightly. What is clear is that most cases of leukemia are not associated with high voltage lines transmission

In a small number of people with very rare diseases or HTLV-1 virus, the risk of acute leukemia is increased.

However, most people with leukemia have no identified risk factors. The cause of their illness remains unknown to this day. Due to the fact that the cause of leukemia is unclear, there are no methods of prevention, with the exception of two important points: avoid smoking and contact with substances that cause cancer, such as gasoline.

How are acute leukemias in adults classified?

Most tumors are classified into stages of disease (I, II, III, and IV), which are based on the size of the tumor and its extent.

This staging does not apply to leukemia because leukemia is a disease of the blood cells that does not usually produce a tumor.

Leukemia affects the entire bone marrow and in many cases, by the time of diagnosis, has already involved other organs in the process. In leukemia, laboratory studies of tumor cells make it possible to clarify their characteristics, which help in assessing the outcome (prognosis) of the disease and choosing treatment tactics.

Three subtypes of acute lymphoblastic leukemia and eight subtypes of acute myeloid leukemia have been identified.

DIFFERENT TYPES OF LEUKEMIA.

There are four main types of leukemia:

acute versus chronic

lymphoblastic versus myeloid

"Sharp" means rapidly developing. Although the cells grow quickly, they are not able to mature properly.

"Chronic" means a condition where the cells appear mature but are actually abnormal (altered). These cells live too long and replace some types of white blood cells.

"Lymphoblastic" and "myeloid" refer to the two different types of cells from which leukemia arises. Lymphoblastic leukemia develops from bone marrow lymphocytes, myeloid leukemia arises from granulocytes or monocytes.

Leukemia can occur in both children and adults, however different types leukemias predominate in one or the other group.

Acute lymphoblastic leukemia (ALL)

Occurs in children and adults

More often diagnosed in children

Represents slightly more than half of all cases of leukemia in children

Acute myeloid leukemia (AML) (often called acute nonlymphoblastic leukemia)

Affects children and adults

Accounts for less than half of all cases of leukemia in children

Chronic lymphocytic leukemia (CLL)

Occurs only in adults

Is detected twice as often as chronic myeloid leukemia (CML)

Chronic myeloid leukemia (CML)

Mainly affects adults and is very rarely detected in children

CLL is diagnosed twice as rarely.

Is early detection of leukemia possible?

Currently, there are no special methods to diagnose acute leukemia at an early stage. Best recommendation is to immediately consult a doctor if any unexplained symptoms appear. People in high-risk groups should be monitored regularly and closely.

How is acute leukemia diagnosed?

Leukemia can be accompanied by many signs and symptoms, some of which are nonspecific. Please note that the following symptoms most often occur with diseases other than cancer.

Common symptoms of leukemia may include fatigue, weakness, weight loss, fever, and loss of appetite.

Most symptoms of acute leukemia are caused by a decrease in the number of red blood cells as a result of the replacement of normal bone marrow, which produces blood cells, with leukemia cells. As a result of this process, the patient's number of normally functioning red blood cells, white blood cells and platelets decreases.

Anemia (anemia)- This is the result of a decrease in the number of red blood cells. Anemia leads to shortness of breath, fatigue and pale skin.

Decreased white blood cell count increases the risk of developing infectious diseases. Although leukemia patients may have very high white blood cell counts, these cells are not normal and do not protect the body from infection.

Low platelet count may cause bruising, bleeding from the nose and gums.

Spread of leukemia beyond the bone marrow to other organs or the central nervous system can cause various symptoms, such as headache, weakness, convulsions, vomit, gait and vision disturbance.

Some patients may complain of pain in bones and joints due to their destruction by leukemia cells.

Leukemia can lead to enlargement of the liver and spleen. If the lymph nodes are affected, they may become enlarged.

In patients with AML gum damage leads to their swelling, pain and bleeding. Skin lesions are manifested by the presence of small multi-colored spots that resemble a rash.

In T-cell type ALL, it is often affected thymus . A large vein (superior vena cava), carrying blood from the head and upper extremities to the heart, runs next to thymus gland. An enlarged thymus gland can put pressure on the trachea, causing coughing, shortness of breath, and even suffocation.

When the superior vena cava is compressed, swelling of the face and upper extremities is possible (superior vena cava syndrome). This can cut off the blood supply to the brain and be life-threatening. Patients with this syndrome should begin treatment immediately.

METHODS OF DIAGNOSTICS AND CLASSIFICATION OF LEUKEMIA.

The presence of some of the above symptoms does not mean that the patient has leukemia. Therefore, additional studies are carried out to clarify the diagnosis and, if leukemia is confirmed, its type.

Blood test.

Changes in the number of different types of blood cells and their appearance under a microscope may suggest leukemia. Most people with acute leukemia (ALL or AML), for example, have too many white blood cells and not enough red blood cells and platelets. In addition, many white blood cells are blast cells (a type of immature cell that does not normally circulate in the blood). These cells do not perform their function.

Bone marrow examination.

A small amount of bone marrow is removed using a thin needle for testing. This method is used to confirm the diagnosis of leukemia and evaluate the effectiveness of treatment.

Lymph node biopsy.

In this procedure, the entire lymph node is removed and then examined.

Spinal tap.

During this procedure, a thin needle is inserted in the lower back into the spinal canal to obtain a small amount of cerebrospinal fluid, which is examined for leukemia cells.

Laboratory research.

To diagnose and clarify the type of leukemia, various special methods are used: cytochemistry, flow cytometry, immunocytochemistry, cytogenetics and molecular genetic studies. Specialists study bone marrow, lymph node tissue, blood, cerebrospinal fluid under a microscope. They evaluate the size and shape of the cells, as well as other characteristics of the cells, to determine the type of leukemia and the degree of maturity of the cells.

Most immature cells are blast cells, unable to fight infection, which replace normal mature cells.

OTHER RESEARCH METHODS.

• X-rays are taken to identify tumor formations in the chest cavity, damage to bones and joints.
• Computed tomography (CT) is special method X-ray examination, which allows you to examine the body from different angles. The method is used to detect lesions in the chest and abdominal cavities.
• Magnetic resonance imaging (MRI) uses strong magnets and radio waves to produce detailed images of the body. The method is especially suitable for assessing the condition of the brain and spinal cord.
• Ultrasound examination (ultrasound) makes it possible to distinguish tumor formation and cysts, as well as the condition of the kidneys, liver and spleen, lymph nodes.
• Lymphatic and skeletal systems: At this method The radioactive substance is injected intravenously and accumulates in the lymph nodes or bones. Allows differentiation between leukemic and inflammatory processes in lymph nodes and bones.

Treatment of acute leukemia in adults

Acute leukemia in adults is not one disease, but several, and patients with different subtypes of leukemia respond differently to treatment.

The choice of therapy is based both on the specific subtype of leukemia and on certain characteristics of the disease, called prognostic features. These features include the patient's age, white blood cell count, response to chemotherapy, and whether the patient has previously been treated for another tumor.

Chemotherapy

Chemotherapy refers to the use of drugs that destroy tumor cells. Typically, anticancer drugs are prescribed intravenously or orally (by mouth). Once the drug enters the bloodstream, it is distributed throughout the body. Chemotherapy is the main treatment method for acute leukemia.

Chemotherapy for acute lymphoblastic leukemia (ALL).

Induction. The goal of treatment at this stage is to destroy the maximum number of leukemia cells in a minimum period of time and achieve remission (no signs of the disease).

Consolidation. The goal at this stage of treatment is to destroy those tumor cells that remain after induction.

Maintenance therapy. After the first two stages of chemotherapy, leukemia cells may still remain in the body. At this stage of treatment, low doses of chemotherapy are prescribed for two years.

Treatment of damage to the central nervous system (CNS). Due to the fact that ALL often spreads into the membranes of the brain and spinal cord, patients are injected with chemotherapy into the spinal canal or given radiation therapy to the brain.

Chemotherapy for acute myeloid leukemia (AML):

Treatment of AML consists of two phases: remission induction and therapy after remission is achieved.

During the first phase, most normal and leukemic bone marrow cells are destroyed. The duration of this phase is usually one week. During this period and for the next few weeks, the white blood cell count will be very low and therefore measures against possible complications. If remission is not achieved as a result of weekly chemotherapy, repeated courses of treatment are prescribed.

The goal of the second phase is to destroy the remaining leukemia cells. Treatment for a week is then followed by a period of bone marrow recovery (2-3 weeks), then chemotherapy courses are continued several more times.

Some patients are given very high doses of chemotherapy to kill all the bone marrow cells, followed by a stem cell transplant.

Side effects.

In the process of destroying leukemia cells, the normal cells, which, along with tumor cells, also have rapid growth.

Cells in the bone marrow, oral and intestinal mucosa, and hair follicles grow rapidly and are therefore exposed to chemotherapy.

Therefore, patients receiving chemotherapy have increased risk infection (due to low white blood cell count), bleeding (low platelet count), and fatigue (low red blood cell count). Other side effects of chemotherapy include temporary baldness, nausea, vomiting, and loss of appetite.

These side effects usually go away soon after chemotherapy is stopped. Typically, there are methods to combat side effects. For example, antiemetic drugs are given along with chemotherapy to prevent nausea and vomiting. Cell growth factors are used to increase the white blood cell count and prevent infection.

You can reduce the risk of infectious complications by limiting contact with germs by thoroughly cleaning your hands and eating specially prepared fruits and vegetables. Patients receiving treatment should avoid crowds and patients with infection.

During chemotherapy, patients may be given strong antibiotics to further prevent infection. Antibiotics may be given at the first sign of infection or even earlier to prevent infection. If the number of platelets decreases, a platelet transfusion is possible, as is a transfusion of red blood cells if there is a decrease and the occurrence of shortness of breath or increased fatigue.

Tumor lysis syndrome is a side effect caused by the rapid breakdown of leukemia cells. When tumor cells die, they release substances into the bloodstream that damage the kidneys, heart and central nervous system. Giving the patient plenty of fluids and special medications will help prevent the development of severe complications.

Some patients with ALL, after treatment, may later develop other types of malignant tumors: AML, non-Hodgkin lymphoma (lymphosarcoma), or others.

STEM CELL TRANSPLANTATION (SCT)

Chemotherapy damages both tumor and normal cells. Stem cell transplantation allows doctors to use high doses of anticancer drugs to improve the effectiveness of treatment. And although anticancer drugs destroy the patient's bone marrow, the transplanted stem cells help restore bone marrow cells that produce blood cells.

Stem cells are taken from the bone marrow or peripheral blood. Such cells are obtained both from the patient himself and from a selected donor. In patients with leukemia, donor cells are most often used, since there may be tumor cells in the bone marrow or peripheral blood of patients.

The patient is prescribed chemotherapy with very high doses of drugs to destroy tumor cells. In addition to this, radiation therapy is given to destroy any remaining leukemia cells. After such treatment, the preserved stem cells are given to the patient in the form of a blood transfusion. Gradually, the transplanted stem cells engraft into the patient's bone marrow and begin to produce blood cells.

Patients who have received donor cells are given drugs to prevent the cells from being rejected, as well as other drugs to prevent infections. 2-3 weeks after the stem cell transplant, they begin to produce white blood cells, then platelets, and eventually red blood cells.

Patients who have undergone SCT should be protected from infection (stay in isolation) until the necessary increase in the number of leukocytes. Such patients are kept in the hospital until the leukocyte count reaches about 1000 per cubic meter. mm of blood. Then, almost every day, such patients are observed in the clinic for several weeks.

Stem cell transplantation is still a new and complex treatment option. Therefore, such a procedure should be carried out in specialized departments with specially trained personnel.

Side effects of TSC.

Side effects of TSC are divided into early and late. Early side effects differ little from complications in patients receiving chemotherapy with high doses of anticancer drugs. They are caused by damage to the bone marrow and other fast-growing tissues of the body.

Side effects can persist for a long time, sometimes years after the transplant. Late side effects include the following:

• Radiation damage to the lungs, leading to shortness of breath.
• Graft-versus-host disease (GVHD), which occurs only when cells are transplanted from a donor. This serious complication occurs when cells of the donor's immune system attack the skin, liver, oral mucosa and other organs of the patient. In this case, the following are observed: weakness, increased fatigue, dry mouth, rash, infection and muscle pain.
• Damage to the ovaries, leading to infertility and menstrual irregularities.
• Damage thyroid gland, causing metabolic disorders.
• Cataract (damage to the lens of the eye).
• Bone damage; If the changes are severe, part of the bone or joint may need to be replaced.

RADIATION THERAPY.

Radiation therapy(usage x-rays high energies) plays a limited role in the treatment of patients with leukemia.

In adult patients with acute leukemia, radiation may be used if the central nervous system or testicles are affected. In rare emergency cases, radiation therapy is prescribed to relieve tracheal compression tumor process. But even in this case, chemotherapy is often used instead of radiation therapy.

OPERATIVE TREATMENT.

When treating patients with leukemia, unlike other types of malignant tumors, surgery is usually not used. Leukemia is a disease of the blood and bone marrow and cannot be cured with surgery.

During the treatment of a patient with leukemia, a small surgical intervention can be used to insert a catheter into a large vein to administer antitumor and other drugs and draw blood for research.

What happens after treatment of acute leukemia?

After completion of treatment for acute leukemia, dynamic observation in the clinic is necessary. Such observation is very important, as it allows the doctor to monitor possible relapse (return) of the disease, as well as side effects of therapy. It is important to tell your doctor immediately if you experience any symptoms.

Typically, relapse of acute leukemia, if it occurs, occurs during treatment or shortly after its completion. Relapse develops very rarely after remission, the duration of which exceeds five years.