Leukemia: diagnosis. Laboratory, differential

Competencies: OK-1, OK-8, PC-3, PC-5, PC-15, PC-17, PC-27

Relevance of the topic. Hemoblastoses are represented by an extensive group of diseases that differ in polymorphism clinical manifestations and are found in the practice of doctors of all specialties.

Target: To study the clinical and laboratory characteristics of acute and chronic leukemia.

Tasks:

1. Understand the etiology, pathogenesis of hemoblastoses.

2. Know the classification and clinical and laboratory diagnosis of acute and chronic leukemia.

3. Do be able to conduct an objective study of patients with this type of pathology.

Control questions on related disciplines studied at previous departments and courses.

What organs are hematopoietic?

Name the cellular composition of the bone marrow.

How does hematopoiesis normally occur?

Explain the structure and function of erythrocytes?

Name the normal values ​​of human red blood.

List the main functions of leukocytes.

What is the normal content of leukocytes in peripheral blood?

Name the leukocyte formula.

What blood cells are granulocytes?

What is the morphological structure of neutrophils?

What is the functional role of neutrophils?

Describe the morphological structure and functions of basophils and mast cells.

Describe the functions and structure of eosinophils.

What is the functional role and structure of monocytes and macrophages?

Describe the structure, types and functions of lymphocytes.

What is the morphological structure of the lymph nodes?

List the anatomical groups of lymph nodes.

Tell us about the structure and function of the spleen?

What is the morphological structure and function of platelets?

Control questions on the topic under study.

What etiological factors can cause the development of leukemia?

Explain the pathogenesis of leukemia.

How are leukemias classified?

What are the main clinical syndromes observed in acute leukemia?

What laboratory syndrome is decisive in the diagnosis of acute leukemia?

Name the stages of acute leukemia

How is leukemic proliferation syndrome clinically manifested?

Name the clinical and laboratory manifestations of hemorrhagic syndrome in acute leukemia.

What is the most characteristic clinical symptom of chronic myeloid leukemia?

Name the laboratory signs characteristic of chronic myeloid leukemia.

What clinical symptom is most typical for chronic lymphocytic leukemia?

What blood picture is observed in chronic lymphocytic leukemia?

What clinical syndromes are observed in erythremia?

Based on what laboratory data can a diagnosis of erythremia be established?

Name the clinical syndromes characteristic of multiple myeloma.

What laboratory data allow to establish the diagnosis of multiple myeloma?

Which diagnostic criterion is decisive in the diagnosis of multiple myeloma?

Hemoblastosis is a group of tumors that arise from hematopoietic cells. They are divided into leukemias and hematosarcomas. Leukemias are tumors of the hematopoietic tissue with primary localization in bone marrow. Hematosarcomas are tumors from the hematopoietic tissue with primary extramedullary localization and pronounced local tumor growth.

All leukemias are divided into acute and chronic. The determining feature is not the speed of the process, but the morphology of the cells that make up the tumor. If the bulk of the cells is represented by blasts, then we are talking about acute leukemia. In chronic leukemia, the bulk of tumor cells are mature and maturing elements.

Etiology of hemoblastoses.

ionizing radiation

Chemical mutagens: toxic substances (benzene), cytostatics.

Viral factor (Epstein-Barr virus)

The role of heredity: genetic defects in hematopoietic germs, immune system chromosomal abnormalities.

Pathogenesis.

The neoplastic growth of all hemoblastoses is based on clonality: each leukemia owes the entire mass of its cells to mutations in their parent single cell. The pathogenetic feature of hemoblastoses is the gradual malignancy of the tumor process, denoted by the term - tumor progression. The patterns of tumor progression are represented by a number of rules:

1. Hemoblastoses go through two stages: monoclonal (benign) and polyclonal (malignant).

2. Inhibition of normal hematopoietic sprouts and, first of all, of the sprout from which hemoblastosis developed.

3. Change of differentiated cells that make up the tumor in chronic leukemia, blast (the onset of a blast crisis).

4. Loss of enzymatic specificity by tumor cells: morphologically, the cells become undifferentiated.

5. The appearance of extramedullary foci of hematopoiesis.

6. Spasmodic or gradual withdrawal of the tumor from cytostatic therapy.

Leukemia can sequentially go through different stages of progression, but sometimes the disease begins with symptoms characteristic of the final stage.

Acute leukemia.

Acute leukemias are a group of tumor diseases of the blood system - hemoblastoses. Acute leukemia are characterized by damage to the bone marrow by morphologically immature - blast - hematopoietic cells and their appearance in peripheral blood. In the future or from the very beginning, infiltration by blast cells of various organs and tissues may occur. All acute leukemias are clonal, that is, they arise from a single mutated cell. Blast cells in all types of acute leukemia are characterized by large size, a large nucleus, which occupies almost the entire cell and is distinguished by a delicate mesh structure of chromatin with large single nucleoli. Cytoplasm of cells in the form of a narrow bluish or gray-blue rim with single small granules.

Classification about based on morphological, mainly cytochemical, immunohistochemical properties of blast cells. Acute leukemias are named after normal blasts of the corresponding hematopoietic sprouts. The belonging of blast cells to a particular line of hematopoiesis, the degree of their differentiation to some extent determines the clinical course of acute leukemia, the therapy program, and the prognosis of the disease. There are the following main forms of acute leukemia (domestic classification):

Acute myeloid leukemias:

Acute myeloid leukemia

Acute promyelocytic leukemia

Acute myelomonoblastic leukemia

Acute monoblastic leukemia

Acute erythromyelosis

Acute lymphoblastic leukemia

Acute undifferentiated leukemia

Acute biphenotypic leukemias.

International Franco-American-British (FAB) classification without fundamental differences with some clarifications on clusters of cell differentiation (immunophenotyping).

clinical picture.

The characteristic onset, specific external signs characteristic of acute leukemia, cannot be found. The diagnosis of acute leukemia can only be established morphologically - by detecting blast cells in the blood or bone marrow.

The following clinical syndromes are distinguished:

1. Anemia syndrome: weakness, dizziness, shortness of breath, tachycardia, headaches, pallor skin, systolic murmur at all points, lowering blood pressure, hemoglobin levels, red blood cells.

2. Hemorrhagic syndrome: skin hemorrhages, bleeding gums, nose and uterine bleeding, bleeding from abrasions, small cuts, etc., caused primarily by thrombocytopenia.

Syndrome of bacterial and viral complications: fever, weakness, sweating, weight loss, manifestations of intoxication, various infectious diseases(Qatar upper respiratory tract, tonsillitis, pneumonia, meningitis, sepsis, etc.)

Syndrome of leukemic proliferation: enlarged lymph nodes, spleen, liver, gingival hyperplasia, skin leukemids, neuroleukemia (leukemic infiltration of the meninges).

During acute leukemia, the following stages are distinguished:

1. Initial - preleukemia. Can only be assessed retrospectively.

2. Advanced stage of the disease. It is characterized by severe inhibition of normal hematopoiesis, significant blastosis of the bone marrow, peripheral blood.

3. Complete (clinical and hematological) remission: no more than 5% of blast cells in the bone marrow punctate.

4. Recovery: complete remission for 5 years.

5. Incomplete remission.

6. Relapse.

7. Terminal phase: no effect of cytostatic therapy.

Forms of the disease according to the results of a study of peripheral blood: 1) aleukemic - without the release of blast cells into the blood; 2) leukemic - with the release of blast cells into the peripheral blood.

Laboratory diagnostics.

Peripheral blood test:

1. Thrombocytopenia

   The number of leukocytes can be different. The leukemic form is distinguished - a significant increase in the number of leukocytes, subleukemic - a moderate increase in the number of leukocytes, normo- or leukopenic - a normal or reduced number of leukocytes.

   presence of blast cells. In the formula, there is a picture of a leukemic failure: there are young - blast cells and mature granulocytes, monocytes, lymphocytes, there are no transitional forms (promyelocytes, myelocytes, metamyelocytes.

Study of sternal punctate: detection and cytochemical analysis of blast cells, immunophenotyping of bone marrow cells.

Principles of therapy.

Induction (obtaining) remission - a combination of various cytostatic drugs according to the chosen program.

Consolidation of remission (consolidation of remission).

anti-relapse therapy.

Symptomatic therapy: treatment of complications.

Bone marrow transplantation.

Forecast.

Depending on the type of leukemia, remission is achieved in 60-70% of patients, 80% of the treated patients experience a relapse, and complete cure in 10-15%.

Relevance of the topic: Hemoblastoses are represented by an extensive group of diseases that differ in the polymorphism of clinical manifestations and are found in the practice of doctors of all specialties.

Target: To study the clinical and laboratory characteristics of acute and chronic leukemia.

Tasks:

1.Understand etiology, pathogenesis of hemoblastoses.

2.Know classification and clinical and laboratory characteristics of acute and chronic leukemia.

3.Be able to conduct an objective study of patients with leukemia.

test questions in related disciplines studied at previous departments and courses:

1. What organs are hematopoietic?

2. Name cellular composition bone marrow.

3. How does hematopoiesis normally occur?

4. Explain the structure and function of erythrocytes?

5. Name normal performance human red blood.

6. List the main functions of leukocytes.

7. What is the normal content of leukocytes in peripheral blood?

8. Name the leukocyte formula.

9. What blood cells are granulocytes?

10. What is the morphological structure of neutrophils?

11. What is the functional role of neutrophils?

12. Describe the morphological structure and functions of basophils and mast cells.

13. Tell us about the functions and structure of eosinophils.

14. What is the functional role and structure of monocytes and macrophages?

15. Tell us about the structure, types and functions of lymphocytes.

16. What is the morphological structure of the lymph nodes?

17. List the anatomical groups of lymph nodes.

18. Tell us about the structure and function of the spleen.

19. What is the morphological structure and function of platelets?

Control questions on the topic under study:

1. What etiological factors can cause the development of leukemia?

2. Explain the pathogenesis of leukemia.

3. How are leukemias classified?

4. What are the main clinical syndromes observed in acute leukemia?

5. What laboratory syndrome is decisive in the diagnosis of acute leukemia?

6. Name the stages of acute leukemia.

7. How is the syndrome of leukemic proliferation clinically manifested?

8. Name the clinical manifestations and causes of hemorrhagic syndrome in acute leukemia.

9. What is the most typical clinical symptom of chronic myeloid leukemia?

10. Name the laboratory signs characteristic of chronic myelogenous leukemia.

11. What clinical symptom is most typical for chronic lymphocytic leukemia?

12. What is the picture of a blood test for chronic lymphocytic leukemia?

13. What clinical syndromes are observed in erythremia?

14. Based on what laboratory data can a diagnosis of erythremia be established?

15. Name the clinical syndromes characteristic of multiple myeloma.

16. What laboratory data allow to establish a diagnosis myeloma?

17. What diagnostic criterion is decisive for the diagnosis of multiple myeloma?

Hemoblastosis is a group of tumors that arise from hematopoietic cells. They are divided into leukemias and hematosarcomas.

Leukemias are tumors of the hematopoietic tissue with primary localization in the bone marrow. Hematosarcomas are tumors of the hematopoietic tissue with primary extramedullary localization and pronounced local tumor growth.

All leukemias are divided into acute and chronic. The determining feature is not the speed of the process, but the morphology of the cells that make up the tumor. If the bulk of the cells is represented by blasts, then we are talking about acute leukemia. In chronic leukemia, the bulk of tumor cells are mature and maturing elements.

Oncological diseases, the source of which is hematopoietic tissue, are common name hemoblastosis. They, in turn, are divided into hematosarcomas and leukemias. With leukemia, the neoplastic process primarily affects the bone marrow, and with hematosarcoma, foci of malignant hematopoiesis are found in other organs. This disease can affect all age groups, including children and young adults.

What are the types of leukemia?

So, leukemia is a malignant tumor that affects the bone marrow. Moreover, at the moment the clonal nature of this disease is not questioned. This means that all tumor cells are clones of one mutated cell. Moreover, they lose their differentiation, and, consequently, all these cells are not able to perform a normal function.

Also, tumor cells have the ability to unregulated proliferation, that is, they multiply uncontrollably, gradually filling the entire bone marrow and suppressing other hematopoietic sprouts. This is followed by metastasis to internal organs where daughter solid tumors are formed. This, in turn, disrupts the normal functioning of the organ.

Back in the middle of the nineteenth century, a classification of leukemias was adopted in hematology, which still has not lost its relevance. According to this system, all leukemias were divided into two large groups - acute and chronic. Moreover, this division does not depend on the nature of the course of the disease, but is determined by the stage at which hematopoiesis fails.

So, if early and less differentiated cells, or blasts, are affected, then leukemia is usually called acute. And if malignant transformation occurs at the stage of maturing blood cells, then leukemia is considered chronic.

In addition, depending on the affected hematopoietic germ, there are:

• myeloid leukemia.
• Myelomonoblastic leukemia.
• monoblastic leukemia.
• Acute erythromyelosis.
• Megakaryoblastic leukemia.
• Lymphoblastic leukemia.
• promyelocytic leukemia.
• plasmablastic leukemia.
• And finally, the most malignant is acute undifferentiated leukemia.

All these types of leukemia can be accurately diagnosed only by microscopy of a bone marrow biopsy.

Clinical diagnosis of leukemia

Clinical diagnosis of leukemia is based on the symptoms and manifestations of the disease, which are evaluated by the doctor by questioning and examining the patient. At the same time, clinicians distinguish the following stages of the disease for the convenience of making a diagnosis and choosing a method of treatment.

Depending on the stage of development of the process, the initial period is distinguished, when the symptoms are hidden or minimal, but leukemia is already beginning to develop. Then comes the stage of detailed clinical manifestations, when the signs of the neoplastic process appear with full force. And, finally, remission follows with successful treatment or the terminal stage, when the patient dies.

The main symptoms that should be addressed to the doctor at the initial stage are reduced only to constant weakness, drowsiness, sweating. These signs are nonspecific and may simply be a manifestation of neurocirculatory dystonia. However, when such complaints are presented, the principle of oncological alertness should be observed and the patient should be examined at least within the clinical minimum:

• Clinical blood test.
• General urine analysis.
• Standard biochemical analysis blood (bilirubin, creatine, cholesterol).
• blood glucose.
• Electrocardiography.
• Fluorography.

At the initial stage, mild anemia and an increase in ESR are often found in the blood.

When the stage of developed clinical manifestations begins, the diagnosis of acute leukemia does not present great difficulties. Often patients note bleeding gums, the appearance of small bruises, nosebleeds. This is due to the fact that the megakaryoblastic germ of hematopoiesis is blocked, as a result of which platelets are formed. It is these blood cells that are responsible for stopping bleeding.

In addition, high fever and infectious complications may occur. The most common of these is ulcerative necrotic angina. This is due to the fact that leukocytes are involved in the process - blood cells responsible for immune response. In fact, the body of a patient with leukemia is defenseless against infectious agents.

One of the first signs of severe anemia begins to appear - dizziness, pallor and dryness of the skin. This is further exacerbated by bleeding. There may be frequent fainting.

Due to the rapid development of the clone of the tumor precursor, malignant cells quickly fill the cavity of the bone marrow. In humans, the bone marrow is located in tubular bones, sternum, pelvic bones and ribs. Therefore, bursting pains in the bones themselves, as well as aching joints, may appear.

Laboratory diagnosis of leukemia

Of course, in the presence of these symptoms, the patient necessarily needs a complete and comprehensive examination. However, the greatest value in terms of the final diagnosis is a clinical blood test with counting leukocyte formula and morphological study of bone marrow biopsy.

AT clinical analysis blood, there will be a decrease in the number of red blood cells and hemoglobin, as well as platelets. Acute leukemia, the diagnosis of which often begins with such an examination, is characterized by the presence of a large number blast cells in capillary blood. Moreover, it is in acute leukemia that the presence of blasts and differentiated cells is noted, while there are no intermediate links of differentiation. It is also characterized by an increase in clotting and bleeding time and an increase in ESR.

But still, the main method of laboratory diagnosis of leukemia remains for many years the study of the bone marrow. It can be obtained by trepanobiopsy. This procedure involves taking a sample of bone marrow from the wing ilium. This manipulation is quite painful and is carried out under local anesthesia. In this case, a small amount of bone marrow is aspirated with a large and long needle or trocar, which is inserted into the bone marrow cavity. This tissue is then subjected to special staining and microscopy. Further, all hematopoietic cells are counted as a percentage. In acute leukemia, the content of blast cells, as a rule, is at least 10-20%.

As can be seen, the laboratory diagnosis of leukemia is difficult, especially in early stages the development of the disease. Therefore, an abbreviated blood test can serve as a screening method that requires minimal costs and is widely applicable for examining large groups of the population. It is also often in clinical practice called "troika". In this case, only three indicators are determined: hemoglobin, leukocytes and ESR. And if deviations from the norm are detected, a more thorough examination is necessary. Often, with leukemia, already at this stage, a sharp increase in the number of leukocytes, an acceleration of ESR and a decrease in hemoglobin are noted. Such diagnostics by blood test is applicable for the annual survey of the population.

Given the non-specificity of the clinical manifestations of acute leukemia, the diagnosis of the disease is based on the phased application of a complex of laboratory and instrumental studies. The first stage of diagnosis is the establishment of the very fact that a patient has acute leukemia using a cytological examination of blood smears and bone marrow. When detected in blood or bone marrow smears? 20% of blast cells, it can be assumed that the patient has acute leukemia.

Differential diagnosis is carried out with diseases and conditions accompanied by an increase in blast cells in the blood and / or bone marrow. To confirm the diagnosis of acute leukemia, a blast crisis of chronic myeloid leukemia, lymphoblastic lymphoma, myelodysplastic syndrome, leukemoid reactions are excluded.

The second stage of diagnosis is the division of acute leukemia into two groups: acute non-lymphoblastic leukemia and acute lymphoblastic leukemia. For this purpose, in addition to cytological, cytochemical and immunological examination of bone marrow samples is carried out.

The third stage of diagnosis is the division of acute leukemia into forms characterized by a certain prognosis and features of therapy. For this, along with the above research methods, cytogenetic, molecular genetic, immunohistochemical and some other methods are also used. A set of methods used in the process of diagnosing acute leukemia is presented in Table 2.

Table 2. Research methods for acute leukemia

Light microscopy of blood and bone marrow smears, histological specimens of bone marrow remains the main method for diagnosing acute leukemia. Detection in blood and/or bone marrow smears? 20% of blast cells is the basis for the diagnosis.

Cytochemical studies of bone marrow smears can identify acute lymphoblastic leukemia and M1-M6 variants of acute non-lymphoblastic leukemia. ALL is characterized by a positive PAS reaction in the form of large granules and blocks. For ONLL - a positive reaction to myeloperoxidase and Sudan B.

The pattern of peripheral blood in patients with acute leukemia is variable. At the onset of the disease in the peripheral blood, there may be a decrease in the level of hemoglobin and the number of red blood cells, thrombocytopenia (rarely thrombocytosis), leukopenia or hyperleukocytosis, neutropenia, a shift in the leukocyte formula to promyelocytes or blasts. Often in the leukocyte formula there is a gap between young (blast cells) and mature granulocytic cells.

Histological research methods are of fundamental importance in the so-called “dry” bone marrow, when it is not possible to obtain a punctate and evaluate the bone marrow morphology. This situation occurs in 10% of cases. In this case, it is carried out cytological examination an imprint of a bone marrow trepanate, and histological and immunohistochemical analysis allows to establish the diagnosis of acute leukemia with a certain accuracy. It should be noted that in some cases the histological picture can be blurred, which requires differential diagnosis with blast crisis of chronic myeloid leukemia, lymphoblastic lymphoma and myelodysplastic syndrome. Histological method also allows you to establish or confirm the assumption of megakaryoblastic leukemia, characterized by myelofibrosis, an increase in reticulin fibers, an increase in blast cells against the background of an increased number of mature or atypical megakaryocytes. The method of immunohistochemistry is especially accurate for the diagnosis of the M7 variant of ONLL.

Ultrastructural cytochemistry makes it possible to determine myeloperoxidase in myeloblasts and megakaryoblasts at early stages of blast cell differentiation and to diagnose M0 and M7 variants of ONLL. The use of this method proved that in 80% of cases with acute undifferentiated leukemia, blast cells contain myeloperoxidase granules, which allows them to be attributed to myeloid forms.

Immunophenotyping of blast cells, especially when using a flow cytometer, makes it possible to subdivide cells into lymphoblasts and myeloblasts, identify M0, M6, M7 variants of ONLL, verify forms of ALL, and diagnose biphenotypic acute leukemia. Simultaneous use of 3 or 4 staining labels makes it possible to detect the expression of a certain combination of clusters of differentiation (CD) on a blast cell, which subsequently makes it possible to trace these cells for the diagnosis of residual disease.

Cytogenetic research methods are necessary to confirm the diagnosis of some forms of acute leukemia (for example, Acute leukemia is a rather rare disease - only 3% of all malignant tumors a person, however, the nonspecificity of the clinical picture with the possible involvement of many organs and systems in the pathological process, a severe, progressive course of the disease in the absence timely diagnosis in the early stages, inevitably leading to the death of the patient, dictates the need for knowledge of the diagnosis of this pathology by doctors of any specialty.

Examine the patient (taking an anamnesis, external examination, percussion and auscultation of internal organs).

Use the data of physical, instrumental, x-ray examination, laboratory data to make a diagnosis.

Taking into account complaints, anamnesis, physical examination data, identify the main clinical syndromes of acute leukemia.

Using indicators of peripheral blood, myelograms, cytochemical studies, set the form of acute leukemia, the stage of the disease, and evaluate the prognosis for a particular patient.

(leukemia, aleukemia, leukemia) - a malignant disease of the hematopoietic system.

Leukemia is a broad group of diseases that differ in their etiology. In leukemias, a malignant clone can originate both from immature hematopoietic cells in the bone marrow and from maturing and mature blood cells.

Flow

In leukemia, the tumor tissue initially grows at the location of the bone marrow and gradually replaces the normal hematopoietic sprouts. As a result of this process, patients with leukemia regularly develop various types of cytopenias - anemia, thrombocytopenia, lymphocytopenia, granulocytopenia, which leads to increased bleeding, hemorrhages, immune suppression with the addition of infectious complications.

Symptoms of leukemia (leukemia)

Metastasis in leukemia is accompanied by the appearance of leukemic infiltrates in various organs - the liver, spleen, lymph nodes, and other organs.

Leukemia classification

There are 5 main principles of classification:

By the nature of the flow

• sharp, from immature cells (blasts), and
• chronic, maturing and mature cells.

It should be noted that acute leukemia never becomes chronic, and chronic never worsens.

According to the degree of differentiation of tumor cells

• undifferentiated,
• blast,
• cytic leukemia;

According to cytogenesis

This classification is based on ideas about hematopoiesis.

From the point of view of this classification, we can talk about the relative transition of chronic leukemia to acute leukemia with continued, long-term action of etiological factors (the action of viruses, ionizing radiation, chemical substances etc.). That is, in addition to disorders of precursor cells of myelo- or lymphopoiesis, disorders characteristic of acute leukemia develop; there is a "complication" of the course of chronic leukemia.

Based on the immune phenotype of tumor cells

At present, it has become possible to carry out more accurate typing of tumor cells depending on their immune phenotype by the expression of CD19, CD20, CD5, immunoglobulin light chains and other antigenic markers.

According to the total number of leukocytes and the presence of blast cells in peripheral blood

• leukemic (more than 50-80×10 9 /l of leukocytes, including blasts),
• subleukemic (50-80×10 9 /l of leukocytes, including blasts),
• leukopenic (the content of leukocytes in the peripheral blood is below normal, but there are blasts),
• aleukemic (the content of leukocytes in the peripheral blood is below normal, there are no blasts).

Morphological features

Main Clinical signs acute leukemias:

• a large number of blast cells and their advantage (more than 30%, more often 60-90%);
• "leukemic failure" - the disappearance of intermediate forms of cells against the background of a large number of blasts;
• simultaneous presence of abasophilia and aneosinophilia;
• rapidly progressive anemia.

The main clinical signs of chronic leukemia (the signs are the same, but exactly the opposite):

• a small number of blast cells or their absence (less than 30%, more often 1-2%);
• the absence of a "leukemic gap", that is, the presence of intermediate cell forms (promyelocytes and myelocytes);
• basophilic-eosinophilic association, that is, the simultaneous presence of basophilia and eosinophilia;
• slowly progressing anemia with an increase in the rate of its development during its exacerbation.

Diagnostics

In the diagnosis of leukemia great importance has a morphological study. The main methods of intravital morphological diagnostics are studies of peripheral blood smears and bone marrow biopsies, which are obtained by trepanation of the iliac crest or puncture of the sternum.

Treatment

In chronic leukemia, supportive tactics are chosen, the purpose of which is to delay or eliminate the development of complications.

Acute leukemia requires immediate treatment, which includes chemotherapy, radiotherapy, followed by transplantation of healthy donor cells.

Acute leukemia

Acute leukemia without treatment is fatal within weeks or months. If treated, the prognosis for children is often favorable. Acute leukemias are divided into myeloid and lymphoid.

Pathogenesis is due to the proliferation of a clone of tumor cells with characteristic cytogenetic disorders, inhibition of normal hematopoiesis, release of blast cells into the blood, their metastasis to other hematopoietic (spleen, liver, lymph nodes) and non-hematopoietic (skin, central nervous system, testicles, lungs) organs.

chronic leukemia

Patients live without treatment for several months and years. Chronic leukemias are divided into myeloid, lymphatic and megakaryocytic.

Etiology

The etiology of leukemia is unknown.

Risk factors

Risk factors for acute leukemia include ionizing radiation, exposure to chemical (including medicinal) substances (benzene, oil distillation products, cytostatics and some other drugs). The likelihood of acute leukemia among patients receiving cytostatic therapy (the so-called secondary leukemia) increases hundreds of times. The interval before the appearance of leukemia after irradiation is 5-10 years, and after chemotherapy - 2 years with a maximum within 6-10 years.

HIV-infected people suffer from primary CNS lymphoma hundreds of times more often than in the rest of the population, and in most cases this tumor is associated with infection with the Epstein-Barr virus.

Leukemia symptoms. Signs of leukemia

The clinical picture is the same for all types of leukemia. The onset of the disease may be sudden. The severe 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 airways by enlarged intrathoracic lymph nodes).

Perhaps the gradual development of the disease. Patients complain of loss of appetite, decreased ability to work, pain in the bones, joints, tumor-like formations in the neck, armpits (enlarged lymph nodes).

Bone marrow failure syndromes in leukemia

Syndromes caused by bone marrow failure resulting from inhibition of normal hematopoiesis by blast proliferation are as follows.

Anemia syndrome : pallor, shortness of breath, palpitations, drowsiness.

Tendency to infections (bacterial, fungal and viral). AT clinical picture observe both mild (local) forms of infections, such as candidal stomatitis, gingivitis, lesions of the mucous membranes caused by the herpes simplex virus, and severe generalized processes (pneumonia, sepsis).

Hemorrhagic syndrome. On examination, petechiae and ecchymosis on the skin are revealed (spontaneous, at injection sites, mechanical friction). Intense nasal and severe internal bleeding (metrorrhagia, gastrointestinal bleeding, cerebral hemorrhage) are possible.

DIC syndrome. In promyelocytic leukemia, DIC often develops.

Signs of a specific lesion

Intoxication: fever, weight loss, loss of appetite, weakness, increased sweating.

Soreness of bones (especially tubular, spine), arthralgia.

Lymphadenopathy. It is possible to increase any group lymph nodes. Characteristic: multiple, dense, elastic, round, can be soldered to each other, different sizes (from 1 to 8 cm); palpation is painless. Enlargement of the mesenteric lymph nodes and hypertrophy of the appendix as a lymphoid organ can cause pain in the abdomen. Hypertrophic intrathoracic lymph nodes can lead to compression of the mediastinum.

The liver and spleen are enlarged.

Neuroleukemia. CNS damage (neuroleukemia) occurs especially often in ALL and significantly worsens the prognosis. The occurrence of neuroleukemia is due to the metastasis of leukemic cells in the membranes of the brain and spinal cord or into the substance of the brain (intratumor, a prognostically more severe type of tumor growth). AT neurological status manifestations of varying severity are possible - from mild cerebral symptoms (headache) to focal lesions (impaired consciousness, visual impairment, discoordination of movements, dysphasia).

Gingival hypertrophy.

Skin leukemids (specific nodules) often occur in myelomonoblastic and monoblastic types of acute myeloid leukemia.

Mediastinum. Hypertrophy of the thymus can cause compression of the mediastinal organs.

Testicles. Possible damage to the testicles (more often with relapses); testicles are enlarged, asymmetrical, painless.

Renal involvement is rare (possible tubulointerstitial nephritis).

Laboratory and instrumental diagnostics leukemia

Leukemia is suspected when there is clinical symptoms and the following changes in peripheral blood: normochromic normocytic anemia; the number of leukocytes can be different - low (below 5 - 109 / l), normal (from 5 - 109 / l to 20 - 109 / l), increased (over 20 o 109 / l, reaching in some cases 200 o 109 / l ); neutropenia (does not depend on the total number of leukocytes); absolute lymphocytosis; thrombocytopenia (almost always present); "leukemic failure" - the presence of blasts, mature forms against the background of the absence of intermediate forms; in acute myeloblastic leukemia, azurophilic granules and Auer rods can be detected.

Bone marrow puncture for leukemia

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

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

Cytochemical examination is the main method for diagnosing forms of acute leukemia. It is carried out in order to identify enzymes specific for various blasts.

Immunophenotyping of blasts is carried out by an automated method on a flow cytometer or by enzyme immunoassay on glass using light microscopy. The method makes it possible to determine the presence or absence of clusters of blast cell differentiation (CD markers) using monoclonal antibodies. It is primarily necessary for the accurate diagnosis of ALL, as well as in difficult cases differential diagnosis acute lymphoblastic and myeloid leukemias. This is a fundamental point, since the treatment of these forms is different.

Cytogenetic study of leukemia cells allows you to determine chromosomal abnormalities and further forecast.

Other Required Primary Leukemia Investigations

Liquor research. Increased cytosis due to blasts indicates neuroleukemia.

X-ray examination of organs chest: expansion of the shadow of the mediastinum due to an increase in the intrathoracic lymph nodes, leukemids in the lungs.

A biochemical blood test, ECG, echocardiography, EEG are necessary to determine the initial indicators of the functions of vital organs and are carried out before and during chemotherapy, since the cytostatics used have cardiotoxic, hepatotoxic and nephrotoxic properties.

Ultrasound: enlargement of the liver and spleen, foci of leukemoid infiltration in parenchymal organs.

Differential diagnosis of leukemia

Infectious mononucleosis may be combined with an enlarged spleen, fever, the appearance of altered lymphocytes (large, with a wide border of cytoplasm, can be mistaken for blasts) against the background characteristic features(cyclicity of the disease, tonsillitis, jaundice, cardiopathy, mononuclear cells in the blood, positive serological reaction for the Epstein-Barr virus).

HIV infection. Generalized lymphadenopathy is characteristic of HIV infection. The final diagnosis of HIV infection is made in the presence of viral markers in the blood.

Pancytopenia - Leading laboratory sign aplastic anemia . A characteristic morphological picture of the bone marrow is the replacement of hematopoietic tissue with adipose tissue, a decrease in cellularity, and the absence of blasts. In history, it is possible to take drugs (toxic substances) that cause aplasia. Pancytopenia can be caused by autoimmune processes associated, for example, with SLE. With appropriate syndromes (damage to the skin, kidneys, of cardio-vascular system) lupus cells are found in the blood. Pancytopenia is characteristic of vitamin B12 deficiency anemia. In history - concomitant pathology, surgery on the gastrointestinal tract. In the clinical picture, there are three leading syndromes - anemia, trophic disorders, funicular myelosis. In the peripheral blood and in the bone marrow - megaloblasts. Positive effect of therapy with vitamin B12, folic acid.

Leukemoid reactions - a significant increase in the number of leukocytes with a shift of the leukocyte formula to the left. The cause of leukemoid reactions can be severe inflammatory diseases, the use of certain medications (prednisolone). Unlike acute leukemia, there are no blast-type leukemoid reactions.