A lesion of the nervous system that complicates leukemia and is caused by the infiltration of leukemia cells into the nervous structures. Manifested by meningeal symptom complex, signs intracranial hypertension, focal neurological deficit, peripheral nerve dysfunction. The diagnosis of neuroleukemia is established according to a neurological examination, analysis of cerebrospinal fluid, cerebral tomography, craniography, and bone marrow puncture examination. Treatment includes the introduction of cytostatics into the spinal space and irradiation of the brain. Prophylactic therapy is effective.

General information

Neuroleukemia (neuroleukemia, NL) is the result of metastasis of leukemia cells to the brain and spinal cord. It is most often a complication of acute lymphoblastic leukemia in children under 15 years of age. Chronic variants of leukemia are complicated by NL much less frequently than acute ones. Most cases occur during the period of remission of the underlying disease; less often, neuroleukemia occurs in acute phase. There are often patients in whom symptoms of central nervous system damage are the first signs of leukemia. The frequency of occurrence of the complication is closely related to the life expectancy of patients (with a rapid progression of leukemia, it does not have time to develop). On average, the incidence of NL among patients with leukemia is 5-10%. The introduction of prophylactic endolumbar infusion of cytostatics into treatment practice allowed the incidence to be reduced to this level.

Causes of neuroleukemia

NL occurs due to secondary lesion central and peripheral nervous system cancer blood cells (myelo-, lymphoblasts). Metastases - infiltrates from blast elements of the blood - can form in the membranes and medulla, spinal roots, cranial and peripheral nerves. Factors that increase the risk of developing neuroleukemia are the patient's childhood, lymphoblastic form of acute leukemia, high leukocytosis at the onset of the disease, and severe hepatosplenomegaly.

Pathogenesis

Penetration of leukemia cells into nerve tissue occurs through contact and diapedesis. In the first case, the cells spread to the meninges from the bones of the skull and spine. When the membranes are destroyed, they infiltrate the underlying medulla. The diapedetic mechanism is caused by increased permeability of the vascular walls, as a result of which blasts circulating with the blood flow pass from the vascular bed into the nervous tissue, forming metastatic infiltrates in it. Morphologically, neuroleukemia is characterized by multifocal leukemic infiltrates, gliosis, and demyelination of nerve fibers. The formation of leukemic foci in the medulla leads to increased intracranial pressure, compression of cerebral and spinal structures, and loss of functions of the affected area. Infiltration of the ventricular system is dangerous due to the development of occlusive hydrocephalus. Infiltrates of nerve trunks cause their dysfunction. Depending on the location of the lesions, a clinical picture is formed, including cerebral and focal symptoms.

Classification

The variety of localization options for leukemic foci leads to wide variability clinical symptoms. Therefore, it is proposed to classify neuroleukemia into the following forms:

• Leukemic meningitis is a consequence of leukemic infiltration of the cerebral membranes. Manifests with acute meningeal symptoms. It may be the first manifestation of an acute form of leukemia.
• Leukemic meningoencephalitis- the result of multifocal damage to the membranes and medulla. A combination of meningitis, intracranial hypertension, and cranial nerve dysfunction is typical.
• Pseudotumorous form occurs less frequently. Caused by the presence of a local leukemic focus. Simulates a clinic.
• Peripheral form occurs when infiltrates are localized in the trunks of peripheral nerves. It occurs as mono- and polyneuropathies.

The IP criteria are clinical manifestations and typical cerebrospinal fluid changes. The presence/absence of these signs formed the basis for the classification of neuroleukemic syndrome into:

• Full- there are clinical symptoms and specific changes in the cerebrospinal fluid.
• Incomplete- there is one of the criteria. Option 1 implies the absence of pathological abnormalities in the cerebrospinal fluid in the presence of clinical manifestations. Option 2 - latent course against the background of typical disorders of the liquor composition.
• Hidden- there is no clinic, the cerebrospinal fluid is normal. Swelling of the optic discs is noted during ophthalmoscopy. According to neuroimaging data, focal changes are detected in the cerebral substance.

Symptoms of neuroleukemia

Cases of meningeal and meningoencephalitic forms of NL have an acute onset. Characterized by intense headache, photophobia, vomiting, increasing lethargy, lethargy. There is an increase in the tone of the occipital muscles. Dysfunction of cranial nerves is caused by their direct damage or compression in conditions of increasing intracranial hypertension. There may be blurred vision, double vision, strabismus, drooping of the upper eyelid, impaired conjugal movement of the eyeballs, facial asymmetry, and hearing impairment. Epileptic seizures are possible.

In the pseudotumor variant, neuroleukemia occurs with a predominance of focal symptoms. Depending on the location of the lesion, unilateral weakness of the limbs (hemiparesis), speech impairment (motor aphasia), extrapyramidal symptoms (hyperkinesis), attacks of Jacksonian epilepsy with convulsions or sensory disorders of 1-2 limbs are observed. The peripheral form is characterized by paresthesia, decreased sensitivity, muscle weakness, decrease tendon reflexes in the zone of innervation of the affected nerves. Manifestations may indicate limited damage to one nerve trunk (eg, tibial nerve neuropathy).

Complications

An increase in leukemic infiltration in the central nervous system leads to the death of neurons with worsening neurological abnormalities and the formation of irreversible disorders. Serious complication is compression of the brain due to growing intracranial hypertension (including through the mechanism of occlusive hydrocephalus). Mass effect with compression of the cerebral trunk provokes a disorder of vital functions and causes death.

Diagnostics

Interpretation of neurological symptoms in patients with established leukemia does not cause diagnostic difficulties. Difficulties in diagnosis are associated with cases where neuroleukemia has undercurrent or is a variant of the debut of hemoblastosis. Diagnostic algorithm includes:

• Examination by a neurologist. Allows you to identify stiffness of the neck muscles, meningeal symptoms of Brudzinsky, Kernig, motor and sensory disorders, speech disorders, pathology of peripheral and cranial nerves. The results obtained allow us to determine the type and level of damage to the NS.
• X-ray of the skull. Determines osteoporosis and porosity of the bones of the arch in patients with a latent form of NL.
• Cerebrospinal fluid examination. The material is obtained by lumbar puncture. Neuroleukemia is characterized by an increase in the number of cellular elements (cytosis) above 5 cells/μl, and the presence of blast cells in the cerebrospinal fluid. Similar changes are observed in 90% of patients.
• Tomographic studies. Neuroimaging methods are crucial in cases of latent neuroleukemia, when identifying changes in the cerebrospinal fluid without a corresponding clinical picture of the disease. CT scan of the brain visualizes foci of infiltration as hypodense. Cerebral MRI confirms the presence of infiltrates and allows a more accurate assessment of their size and location. However, neuroimaging does not diagnose the nature of infiltrates, and therefore is interpreted in conjunction with other diagnostic data.
• Sternal puncture. Necessary for obtaining a bone marrow sample and its subsequent analysis. The results of a myelogram can confirm the presence of leukemia and assess the state of hematopoiesis.

Neuroleukemia must be differentiated from brain tumors, meningitis and encephalitis of infectious etiology, the peripheral form - from Guillain-Barré syndrome, polyneuropathies of other origins.

Treatment of neuroleukemia

Therapy is carried out by specialists in the field of hematology and neurology with the participation of radiologists. Treatment difficulties are caused by poor permeability of the blood-brain barrier to antitumor pharmaceuticals. The basic method is endolumbar administration of cytostatics (methotrexate) in combination with cranial irradiation. During treatment, complete sanitation of the cerebrospinal fluid is achieved. Radiation therapy promotes the death of the resulting tumor infiltrates. According to indications, together with a cytostatic agent, it is additionally administered antitumor drug(cytarabine) or glucocorticosteroid (prednisolone). Intrathecal administration is canceled after three times normal results of cerebrospinal fluid analysis are obtained.

Side neurotoxic effects of cytostatic and radiological therapy can cause a temporary deterioration in the general condition of the patient. Along with basic therapy, cupping is carried out adverse reactions, symptomatic therapy with anticonvulsants, dehydrating agents, etc.

Prognosis and prevention

Usually complex active treatment allows you to achieve regression of neurological symptoms within 3-4 weeks. The further prognosis is closely related to the course of the underlying disease. Often, neuroleukemia can be prevented by timely preventive therapy, which is recommended to begin during the period of induction of remission. Preventive therapy includes a course of endolumbar administration of a cytostatic drug with repeated single infusions during reinduction treatment.

Neuroleukemia syndrome or neuroleukemia is called specific lesion central nervous system (cranial nerves, brain and its membrane) cancerous tumors of the blood.

This disease is classified as a severe exacerbation acute leukemia. It is most often detected in children younger age and teenagers under 15 years of age.

Mechanism and causes of the disease

Neuroleukemia can develop against the background different types acute leukemia, but most often it is diagnosed in children due to lymphoblastic leukemia.

Neuroleukemia develops as a result of blast cells entering the membrane of the brain or spinal cord, into the brain substance itself, as well as the nerve trunks in the first stages of disease progression.

Leukemia cells enter the central nervous system in two ways:

• contact- from the bones of the spine and cranium on the membrane of the brain and nervous system of the spinal cord;
• diapedetic– through the blood vessels of the soft membranes into the brain and cerebrospinal fluid.

The incidence and development of neuroleukemia is associated with the life expectancy of patients with leukemia. According to According to statistical data, the patient’s life expectancy significantly increases the likelihood of developing leukemic damage to the central nervous system.

Of those children who lived for one year, neuroleukemia was found in 27%; if survival reached three to five years, then the likelihood of the disease increasing to 71 and 93%, respectively.

Accurate evidence about the reasons of this disease not available. But medical experts identify several factors that contribute to the appearance of malignant tumors in organism.

The main cause is said to be ionizing radiation. Acute leukemia is often detected in people who were at a distance of up to 1.5 km from the epicenter of radiation. The disease is also highly likely to affect patients with problems in the spine who have undergone radiation therapy.

It is possible that the disease develops due to viruses. Oncogenes provoke cells to constantly divide and form malignant genes.

Often the disease is diagnosed in people whose families had relatives with a similar pathology. Therefore, neuroleukemia may be a hereditary cause.

Among patients, cases of changes at the genetic level were identified: a cancerous formation may subsequently arise from a transformed cell during leukemia. The process of division of such cells leads to an exacerbation of the disease and neuroleukemia.

Types of disease and symptoms

In the first stages of the development of the disease in children, it manifests itself. They become withdrawn, drowsy and moody, and get tired quickly. The further development of the disease is influenced by the scale of leukemic lesions of the central nervous system. There are the following main types of neuroleukemia:

• meningeal - damages the meninges;
• encephalitic – affects the brain;
• mixed form;
• damage to components of the nervous system.

The most common type of leukemic damage to the central nervous system in children is leukemic meningitis, which is diagnosed when tumor cells are detected in the cerebrospinal fluid.

In this situation, patients are often also diagnosed with pinched cranial nerves. Swelling of the eye discs, as well as disruption of the muscles that control eye movements, cannot be ruled out. Damage to the bone marrow can trigger seizures.

The manifestation of neuroleukemia is often similar to the symptoms of damage to the meninges: chronic, weakness, vomiting, loss of consciousness, swelling of the head optic nerve, deviation of the visual axis. Lymph nodes are slightly enlarged, bruises appear on the skin.

If the brain substance is damaged, then seizures and inappropriate behavior appear.

The disease affects the cranial nerves, causing impairment of the facial muscles, visual impairment and hearing impairment.

The initial sign of neuroleukemia is an increased content of blast cells and cytosis in the cerebrospinal fluid.

Diagnosis and treatment

Diagnosis of neuroleukemia is carried out using cytological examination cerebrospinal fluid to detect leukemic cells. Often, the protein content in this situation will be increased, and the glucose content will be decreased.

The modern course of treatment is aimed at achieving the following objectives:

• reduction of disease symptoms;
• containment of the results obtained - preventing deterioration of the patient’s condition;
• timely implementation of treatment procedures in case of relapse.

The essence of treatment for neuroleukemia is the introduction of chemotherapy drugs into the cerebrospinal fluid. If there is no effect from lumbar puncture, radiation is prescribed.

Forecasts - is there a chance?

Talk in advance about the results of treatment such dangerous disease, like neuroleukemia, is quite difficult. For efficiency healing process affects a number of reasons, and not only medical ones. Cancer diseases are prone to recurrence, therefore, the earlier treatment is started, the higher the chances of recovery or remission.

The life prognosis, as well as how long it will take to die from neuroleukemia, is largely determined by the following factors:

• person's age;
• chosen method of treatment;
• complexity of the disease and its stage;
• the patient’s immunity, the body’s response to chemotherapy and radiation.

A favorable outcome largely depends on achieving complete clinical and hematological remission. Children aged 2 to 5 years have twice the chance of survival than newborns and schoolchildren.

Modern medicine can bring the patient’s condition to stable remission. Patients under 55 years of age can expect to live about five more years. How older person, the lower his chances of recovery. No more than 10% of patients over the age of 60 have a life expectancy of up to five years.

A worsening prognosis may be caused by a violation of the treatment strategy, intervals between courses, or non-compliance with the dosage of medications. This leads to the resistance of leukemia cells and the futility of further therapy.

Blood diseases in childhood account for approximately one sixth of all groups of diseases. The most common among them is anemia (anemia) - a pathological condition in which the level of hemoglobin, which is involved in the transport of oxygen to tissues and organs, decreases. Many diseases of the hematopoietic system respond well drug correction at the initial stage, but for some diseases, even timely seeking medical help cannot guarantee a favorable prognosis for life and health. Such pathologies include leukemia.

Leukemia (another name is leukemia) is a systemic disorder of the hematopoietic system, in which a large number of immature white blood cells (leukocytes) are released into the bloodstream from the bone marrow, unable to perform the functions of mature ones. cellular structures. For this reason, leukemia is often called leukemia. It can occur in two forms, but in children, acute leukemia is diagnosed in 80% of cases. IN advanced cases The life prognosis rarely exceeds 1-2 years, so timely diagnosis of pathology is a prerequisite for increasing the chances of recovery and long-term remission.

In childhood, leukemia is usually detected quite early: the main group of patients consists of children aged 1 to 5 years, as well as infants in the first year of life. In approximately 20% of cases, leukemia is congenital disease, and the newborn is born with severe systemic disorders of the hematopoietic system, which affects the rate of physical and mental development, as well as condition immune system. Leukemia is a malignant disease, but it is not included in the group of tumor diseases, so the term “blood cancer” is used unjustifiably in relation to this group of pathologies.

The most common form of leukemia is lymphoblastic leukemia, which is the release of immature lymphocytes into the blood. Myeloblastic (myelogenous) leukemia is characterized by the release of stem cells differentiated according to the granulocytic type - myeloblasts. The risk of pathology increases in children born as a result of multiple pregnancies, suffering from Down syndrome and various forms children's cerebral palsy and those with low birth weight.

Both spicy and chronic course The disease has three stages, very different in clinical course and forecast later life. In the vast majority of cases, the disease is detected before the age of two.

Stages of leukemia in children

Stage/phase	What is it characterized by?
Initial (latent)	There are no specific symptoms at this stage. The only indirect signs may be a slight deterioration in health, weakness, frequent drowsiness, problems with appetite
Expanded (sharp)	The symptoms are clearly expressed, the clinical picture includes everything typical symptoms diseases. Changes are clearly visible when analyzing the chemical composition of the blood and leukocyte formula
Terminal	The child has absolute alopecia (all hair falls out), and the body is covered with a characteristic rash. Terminal leukemia is incurable, since at this stage there is active metastasis of malignant cells to other organs and tissues.

Important! Children whose leukemia was detected in a latent form have the greatest chance of recovery. To prevent the progression of the disease, it is necessary to regularly take blood tests (2-4 times a year) and pay attention to any symptoms indicating possible defeat hematopoietic system.

Leukemia in children: clinical picture

The clinical picture of leukemia in young patients with progressive forms of pathology is quite pronounced, which allows specialists to suspect and diagnose leukemia in a timely manner. Almost all symptoms of the disease are caused by a large number of lymphoblasts in the blood, which not only cannot provide sufficient protection against pathogens, but are also unable to provide essential functions red leukocytes, for example, transport oxygen and nutrients.

Skin signs

The most characteristic and typical for any stage of leukemia are changes in the skin. They become pale, dry, and peeling appears in some areas. The scalp also begins to peel off, since the hair bulbs and follicles do not receive the necessary vitamins, which negatively affects the nutrition of the epidermis and the condition of the hair. Paleness in leukemia is unnatural; at an advanced stage, the child may develop cyanosis - blueness of the skin caused by a rapid increase in carboxyhemoglobin in the blood. Carboxyhemoglobin is hemoglobin combined with carbon monoxide molecules. If the concentration of carbon monoxide reaches critical values, the child will simultaneously skin symptoms Other signs will also appear, for example:

• headaches, migraine;
• dizziness (with severe leukemia - loss of consciousness);
• nausea and associated refusal to eat.

Second typical sign malignant blood lesion - skin rash. The skin in these areas may change color, peel, or become bruised.

Important! If parents do not consult a doctor promptly when areas with a bluish discoloration appear, there is a risk of death caused by acute carbon monoxide poisoning.

Tendency to bleed

Children, even with initial forms of leukemia, often experience nosebleeds. Copious bleeding from the nasal passages can begin even with minor exposure - such a symptom always indicates pathologies in the functioning of the body, so it should never be ignored. Indirect sign malignant blood lesions can also cause bleeding gums, therefore, if there is frequent admixture of blood while brushing teeth, parents should show the child to the dentist and exclude possible inflammatory diseases gums (gingivitis, periodontitis).

Blood in leukemia may be present in small quantities in the sputum discharged from the throat during a dry or wet cough. Sometimes this sign is a symptom of inflammatory diseases of the bronchopulmonary tissue or mucous membranes of the larynx, but only a doctor can exclude the possibility of leukemia after laboratory and hardware diagnostics.

Note! At malignant diseases blood, frequent bleeding is usually accompanied by bruises and hematomas that occur in various parts of the body, regardless of external influence. This is a dangerous sign that requires consultation with a pediatric hematologist.

Pain syndrome

Leukemia itself does not cause pain, but the child may complain of similar symptoms if other organs are affected. In approximately 35% of children, acute forms of leukemia are accompanied by an enlargement of the liver and spleen, so the child may complain of dull pain in the right hypochondrium, abdominal space and in the center of the umbilical line. If the disease has already entered the metastasis stage, bone and joint tissue are most often affected, so joint pain bothers almost half of patients with end-stage leukemia.

Clinically this is manifested by the following symptoms:

• limited mobility (the child may limp and refuse to participate in outdoor games);
• muscle weakness (it is difficult for a child to hold even light objects in his hands);
• tics and twitching (rare - no more than 5-10% of children).

Pain syndrome should always be assessed in accordance with other signs and symptoms, since this sign itself is not very informative.

Video - What are the symptoms of leukemia in children?

How does the immune system react?

As a result of a rapid increase in the concentration of leukocytes in the blood, a child may develop secondary immunodeficiency syndrome. The body's protective functions weaken, which leads to frequent illnesses infectious etiology. These may be infections:

• oral cavity (recurrent stomatitis, herpes, glossitis);
• respiratory system (chronic tonsillitis, chronic and obstructive bronchitis, bronchial-type asthma, hypertrophic rhinitis, pneumonia);
• stomach and intestines (gastritis, intestinal infections, rotavirus disease).

If a child gets sick more than 4-6 times a year, it is necessary to undergo examination by an immunologist and determine the immunological status. Most often, the initial forms of leukemia are identified during a consultation with an immunologist about frequent respiratory infections in a child.

Important! Approximately 22% of children with leukemia die as a result of infectious lesions of the respiratory system or intestines due to acute blood poisoning (sepsis). Immature lymphoblasts cannot restrain the growth of pathogenic flora and prevent its penetration into the systemic bloodstream, which leads to the development of severe inflammatory reaction and the death of a child. Such risks can be minimized by constantly using gauze bandages and maintaining sterility in the room where the patient is.

Symptoms of the heart and blood vessels

In almost all children, leukemia is accompanied by changes in the functioning of the heart muscle, since the main source of nutrition and oxygen supply for the main “pump” human body is blood. The child may complain of typical disturbances in the functioning of the heart: shortness of breath, frequent dizziness, pain in the heart area and chest. He experiences severe fatigue even after minimal exercise. physical activity, severe arrhythmia and tachycardia occur. Blood pressure in such children is rarely stable: most often the disease is characterized by either surges or systemic hypotension. Heart problems lead to difficulty falling asleep and insomnia. The child may wake up frequently at night due to nocturnal shortness of breath and increased heart rate.

Neuroleukemia syndrome.

A form of neuroleukemia. Meningial. Encephalitic. Meningo-encephalitic. Meningo-encephalomyelitis. Encephalomyelitis. Diencephalic syndrome. Myelitic. Epidurit. Plexit. Polyradiculoneuritis

Clinical symptoms acute leukemia depends on the degree of inhibition of normal hematopoiesis and the severity of extramarrow manifestations. It is difficult to indicate another similar disease in which the symptoms would be as diverse as in acute leukemia. This has been repeatedly emphasized by pathologists and clinical hematologists. P.A. Barkhash wrote: “Each case of acute leukemia is so diverse that it must be described.” It should be emphasized that there are no absolutely pathognomonic symptoms of acute leukemia, this especially applies to the initial period of the disease. The following options for the initial period of acute leukemia can be distinguished:

Acute onset of the disease - observed in 1/2 of patients and is characterized by high temperature body, severe weakness, intoxication, joint pain, pain when swallowing, abdominal pain. This onset of the disease is usually interpreted as influenza, sore throat, rheumatism, acute respiratory disease, and in case of abdominal pain it is mistaken for acute appendicitis. At acute onset diseases correct diagnosis acute leukemia is usually diagnosed no earlier than 2-3 weeks after the first symptoms appear;

The onset of the disease with severe hemorrhagic phenomena is observed in 10% of patients and is characterized by bleeding of various locations (nasal, gingival, gastrointestinal, etc.), the appearance of hemorrhagic rashes on the skin;

Slow onset - characterized by the development of a nonspecific symptom complex: increasing weakness, progressive decrease in performance, severe fatigue, pain in bones, muscles, joints, slight enlargement of lymph nodes, moderate hemorrhagic manifestations and the appearance of small hemorrhages on the skin in the form of bruises. With a slow onset of the disease, the correct diagnosis is usually made after 4-6 weeks, and peripheral blood testing plays a decisive role;

Asymptomatic (hidden) onset - observed in 5% of patients, the general condition of the patients is not disturbed, the state of health is quite satisfactory, an objective examination, as a rule, does not reveal significant changes, sometimes in some patients a targeted examination can reveal a slight enlargement of the liver and spleen. The disease is detected by random examination of peripheral blood.

The initial period is characterized by varying lengths from several weeks to several months. Periods of deterioration are followed by short-term improvement.

Stage of the developed clinical picture of acute leukemia- this is a consequence of intense proliferation, accumulation of malignant leukemic cells and pronounced extramarrow manifestations. Patients complain of pronounced progressive weakness, fatigue, pain in the bones and joints, pain in the liver and spleen, fever, headache, pallor, and swollen lymph nodes.

Clinically, the symptoms of the advanced period of the disease can be grouped into the following main syndromes: hyperplastic or proliferative, hemorrhagic, anemic, osteoarticular, intoxication, immunodeficiency.

Pulmonary-pleural and cardiovascular syndromes are less common.

Hyperplastic syndrome caused by leukemic tissue infiltration. It is characterized painless increase lymph nodes, liver and spleen. Lymph nodes have a dense consistency, painless, mobile, not fused to each other and the surrounding tissue. Some The lymph nodes expressed everywhere in sizes from 1.0 x 2.0 to 3.0 x 4.0 cm, in others isolated conglomerates are found in the neck, axillary region, mediastinum, and abdominal cavity. The lymph nodes in the neck area are most often enlarged. Severe enlargement of the lymph nodes in the mediastinum can lead to compression of the superior vena cava and disruption of the outflow of blood into the right atrium with the development of superior vena cava syndrome: shortness of breath, cyanosis, swelling of the neck, swelling of the jugular veins. Hyperplastic syndrome is also characterized by gingival hyperplasia and the development of severe ulcerative-necrotic stomatitis, which is observed in severe cases of the process and is regarded as an unfavorable diagnostic sign. In this case, ulcerative-necrotic damage to the tonsils and oral mucosa occurs, spreading to the pharynx and esophagus. The tonsils enlarge, become loose, and can make breathing difficult.

Leukemic infiltration liver disease is observed in almost all forms of acute leukemia, as well as with the development of blast crisis in patients with chronic myeloid leukemia, and can be diffuse or focal. Diffuse leukemic infiltration is more natural. In acute myeloid leukemia, the most typical location of leukemic infiltrates is in the perivascular spaces, while in acute and chronic lymphocytic leukemia, it is predominantly in the portal fields. Hepatomegaly may also result from hepatocyte hypertrophy in leukemia. Upon palpation, the dense consistency of the liver is determined, its surface is usually smooth, and it is rarely painful. The liver can protrude 3-7 cm below the edge of the costal arch. The functional capacity of the liver is impaired in varying degrees. Sometimes, despite significant hepatomegaly, its function suffers slightly. The most important manifestation of severe liver dysfunction is jaundice and should be considered different genesis. Jaundice can be caused by the addition of viral hepatitis, bacterial cholangitis, or the toxic effects of cytostatic therapy. One of the causes of jaundice may be obstruction of the biliary tract by enlarged lymph nodes, as well as hemolysis of red blood cells.

Leukemic infiltration spleen in the form of its enlargement varying degrees severity is observed in almost all patients with acute leukemia. In acute myeloblastic leukemia, and less commonly in lymphoblastic leukemia, splenic infarctions may develop due to impaired blood flow in it due to leukemic infiltrates and cell aggregates. Splenic infarction manifests itself intense pain in the area of ​​the left hypochondrium, enlargement of the spleen, the appearance of a peritoneal friction noise above the surface of the spleen. Splenic infarction is easily recognized using ultrasound diagnostics.

Enlarged mesenteric lymph nodes can cause abdominal pain.

Severe pain appears when the bones are beaten due to the development of subperiosteal leukemic infiltrates. Leukemic infiltrates appear on the skin in the form of leukemids - widespread reddish-bluish papulous plaques.

Severe manifestations of hyperplastic syndrome are also severe painful infiltration of the testicles and damage to the nervous system - neuroleukemia.

Hemorrhagic syndrome observed in 50-60% of patients with acute leukemia and is the most important manifestation of the disease. It is caused by thrombocytopenia, increased permeability and decreased resistance of the vascular wall, impaired coagulation activity of the blood due to a deficiency of coagulation factors V, VII, prothrombin, fibrinogen, and increased fibrinolytic activity.

Intensity hemorrhagic manifestations very variable: from single petechial rashes on the skin and mucous membranes to extensive intradermal hemorrhages and nasal, gingival, less often gastric, intestinal bleeding. The severity of bleeding varies.

Anemic syndrome naturally develops in all patients with acute leukemia, due to a sharp reduction in the red hematopoietic germ in the bone marrow (due to progressive infiltration of malignant leukemic bone marrow tissue), intoxication and bleeding. The severity of anemia clearly correlates with the degree of proliferation of leukemia cells in the bone marrow. Children experience pallor of the skin and mucous membranes, increasing weakness, dizziness, headache, fatigue, and loss of appetite. A systolic murmur is heard at the apex of the heart.

Intoxication syndrome accompanies the advanced clinical period of acute leukemia and is characterized by increasing general weakness, high body temperature, sweating (especially at night, when the sweat becomes heavy), headache, lack of appetite, weight loss, ossalgia, nausea and vomiting.

In acute leukemia, it develops immunodeficiency state, characterized by a sharp disruption of cellular and humoral immunity, phagocytic function of leukocytes, decreased complement activity. All this creates the preconditions for the development of various infectious diseases. inflammatory processes, which, as a rule, take a severe course, often developing a septic condition. Infectious and inflammatory diseases, primarily severe pneumonia, often lead to the death of patients. However, it should be taken into account that fever can be a manifestation of leukemia, transfusion reaction, splenic infarction, thrombophlebitis, which requires differential diagnosis with infectious and inflammatory diseases.

Fever due to leukemia itself differs from infectious-inflammatory fever the following features:

Body temperature daily is higher than 38.7°C;

Duration of fever for more than 2 weeks;

There are no clinical manifestations of infection, allergic mechanisms of fever;

There is no positive therapeutic response to empirical antibiotic therapy;

Fever disappears quickly after taking non-steroidal anti-inflammatory drugs;

Blood and urine cultures for bacteria, fungal flora, and viral infection are negative;

Program treatment of acute leukemia with cytostatic agents causes stable normalization of temperature.

Patients with acute leukemia often develop syndromic neutropenia, in which there is a high risk of developing infectious and inflammatory processes. Most common pathogens, which are the cause of fever in neutropenia, are gram-negative (Pseudomonas aeruginosa, Escherichia coli, Enterobacter, Proteus); gram-positive ( Staphylococcus aureus, epidermal staphylococcus, viridans streptococcus, pneumococcus), anaerobic cocci and bacilli.

Osteoarticular syndrome. Bone damage is often observed in acute leukemia and manifests itself as pain in the bones (in children, more often in the area of ​​long tubular bones, in adults - in the area of ​​\u200b\u200bthe ribs, vertebrae), sometimes pathological fractures, due to severe osteoporosis. Changes in the skeletal system are more often observed in acute lymphoblastic leukemia. Bone pain is caused by cortical destruction and periosteal layers, back pain is associated with damage to the vertebrae. Bone involvement is diagnosed based on clinical manifestations and bone radiography. When X-ray examination of the skeletal system in patients with leukemia, 4 types of changes are detected: osteoporosis is most often detected, osteosclerosis is less often detected, in addition, destructive changes (osteolysis) and periosteal reactions with bone tumors are found. Characterized by increased transparency and reduction of vertebral bodies.

Under neuroleukemia(neuroleukemia) understand the development of leukemic infiltration in the membranes and substance of the brain and spinal cord, in nerve trunks, ganglia of the autonomic nervous system, which is caused by metastasis of blast cells. The first way of metastasis of blast cells is contact, from the bones of the skull, spine to hard shell and the dural infundibulum of the cranial and spinal nerves. The second route of metastasis is diapedetic - from the vessels of the pia mater into the cerebrospinal fluid and brain matter.

Neuroleukemia occurs in 12-18% of patients with acute leukemia and sharply worsens the prognosis. Neuroleukemia most often develops in T-ALL, monoblastic and myelomonocytic leukemia. Clinical manifestations of neuroleukemia depend on its severity and localization of leukemic infiltrates. There are several clinical forms neuroleukemia.

Meningeal form of neuroleukemia manifested by intense headaches (initially episodic, and after 1-2 weeks constant and very strong), nausea, vomiting, severe photophobia, hyperalgesia, symptoms of irritation of the meninges (stiffness of the neck muscles, positive symptom Kernig). There are symptoms of increased intracranial pressure ( stagnant discs optic nerves during ophthalmoscopy, the appearance of finger-like impressions on radiographs of the skull). When examining the cerebrospinal fluid, pleocytosis due to blasts is revealed (the number of blasts in 1 μl ranges from several tens to several thousand), an increased amount of protein, and a reduced amount of glucose.

Encephalitic form of neuroleukemia characterized by symptoms of brain damage. Patients develop intense headaches, sleep disturbances (drowsiness or insomnia), delirium is possible, and patients are often markedly lethargic. Focal symptoms appear in the form of signs of damage to the nuclei of the cranial nerves, paresis of facial muscles, and tongue. Tonic-clonic seizures, hemiparesis, and motor aphasia may occur. When examining the cerebrospinal fluid, a small amount of protein is detected, an increase in glucose levels with normal cytosis.

Meningoencephalitic form of neuroleukemia clinically manifested by a combination of symptoms of meningeal and encephalitic forms, and when examining the cerebrospinal fluid, pleocytosis, protein-cell dissociation, and a decrease in glucose levels are determined.

Diencephalic form of neuroleukemia develops when the diencephalic-mesencephalic region is damaged and is manifested by pathological drowsiness, impaired thermoregulation (hyperthermia, distortion of the normal daily temperature rhythm, isothermia), the development of bulimia (while in the absence of neuroleukemia, appetite is sharply reduced or even absent), thirst, polyuria, impaired dermographism , increased blood pressure. Damage to the mesencephalic zone can manifest as eyelid ptosis and upward gaze paresis. Examination of the cerebrospinal fluid reveals normal or slightly increased cytosis, increased protein levels, and decreased glucose levels.

Meningomyelitic form of neuroleukemia characterized by the appearance of lower paraparesis, gait disturbance, severe dysfunction of the pelvic organs, and the development of radicular symptoms. Examination of the cerebrospinal fluid reveals normal cytosis and a significant increase in protein content (protein-cell dissociation), increased glucose content.

Polyradiculoneuritic form of neuroleukemia leads to dysfunction of various cranial nerves, sensitivity in the distal parts of the arms and legs, reduction or disappearance of tendon reflexes, and often pain on palpation of the nerve trunks.

To diagnose neuroleukemia, in addition to a thorough neurological examination, data from cerebrospinal fluid analysis, neuro-ophthalmological examination, and computed tomography of the brain are used. Of particular importance is the study of the cellular composition of the cerebrospinal fluid; often, to more accurately determine whether cells belong to one or another type of blast, it is necessary to use monoclonal antibodies, a cytogenetic method, and the determination of nuclear terminal deoxynucleotidyl transferase (TdT). The use of these methods is especially important for diagnosing damage to the nervous system in the early stages of the disease and when the clinical symptoms of neuroleukemia are minimal.

Damage to the digestive organs. Leukemic infiltration of the esophagus is a rare manifestation of leukemia, but dysphagia has been described in acute lymphocytic leukemia.

Leukemic infiltration of the intestine is found in acute leukemia quite often, and small intestine is affected more often than fat. One of the most dangerous complications is necrotizing enterocolitis.

Testicular infiltration unilateral or bilateral, can also be observed during the first attack, although more often it is a reflection of a relapse of leukemia. Most often, testicular involvement is observed in acute lymphoblastic leukemia (usually in T-ALL, pre-B-ALL and O-ALL); among non-lymphoblastic forms, testicular infiltration is observed in myelomonocytic leukemia. Leukemic infiltration of the testicles is manifested by their enlargement, often one-sided. The enlarged testicle is dense, usually painless (pain on palpation is less common). The skin over the affected testicle has a cyanotic tint. The leukemic nature of testicular lesions can be proven by the results cytological analysis testicular punctate. In the presence of leukemic infiltration of the testicles, the likelihood of leukemia relapse increases. In some patients, along with enlargement of the testicles, enlargement of the epididymis is also observed.

Leukemic infiltration of the ovaries, especially in the initial period of leukemia, it is rarely diagnosed intravitally. Clinically, ovarian damage is characterized by their enlargement (the left ovary is often involved). In some patients, an enlarged, dense, painless ovary can be felt by palpating the abdomen in the iliac region. Ovarian enlargement is usually detected during gynecological and ultrasound examination.

Kidney damage. Leukemic infiltration of the kidneys in acute leukemia is more often observed in the form of focal proliferations, but in some cases diffuse infiltration of the kidneys and an increase in their size are observed. There are no clinical and laboratory connections between the degree of kidney enlargement and the severity of renal dysfunction. Most often, kidney damage is manifested by changes in urine, and extrarenal symptoms ( arterial hypertension, swelling) are absent. More severe kidney damage is manifested not only by proteinuria, microhematuria, but also by increased blood pressure, the appearance of edema, and hyperazotemia. Severe kidney damage can lead to acute kidney failure.

Lung damage. In acute leukemia, proliferation of blast cells is observed in the interalveolar septa, in peribronchial, perivascular tissue. More often these changes occur in acute lymphoblastic leukemia and less often in acute myeloid leukemia. Clinically, leukemic infiltration of the lungs is manifested by cough, shortness of breath, crepitus or fine rales in various parts of the lungs. Diffuse leukemic infiltration of the lungs can lead to severe respiratory failure restrictive type. In patients with acute lymphoblastic leukemia, compression of the bronchi by enlarged mediastinal lymph nodes and leukemic infiltrates is possible. Some patients experience focal or diffuse leukemic infiltration of the pleura, which is clinically manifested by symptoms of fibrinous or exudative pleurisy.

To diagnose damage to the pleura and lungs in leukemia, X-rays of the lungs, analysis of sputum and pleural fluid are used (blasts can be detected).

Leukemic infiltration heart disease in acute leukemia is rarely determined. Changes in the cardiovascular system in patients with leukemia are mainly due to intoxication, anemia, and hemorrhages in the heart muscle. The most typical features are muffled heart sounds, systolic murmur over the apex and base of the heart, expansion of the boundaries of cardiac dullness, tachycardia, vascular pulsation; vascular thrombosis and thrombophlebitis are also possible. Symptoms of exudative pericarditis may develop when the pericardium is involved in the pathological process. In patients with acute leukemia, complete atrioventricular block has also been described due to leukemic infiltration of the interventricular septum, and the lesion sinus node manifested by sick sinus syndrome, various disorders heart rate. Register diffuse changes on ECG, decreased ejection fraction according to echocardiography.

Defeat eye. Leukemic infiltrates can be found in various parts of the eyes, most often in the area choroid, retina, optic disc, vitreous body, anterior part of the eye. Clinically, this is manifested by pain in the eyes, photophobia, lacrimation, and decreased visual acuity. An ophthalmological examination reveals intense conjunctival injection, anisocoria, iris infiltration, and corneal edema. Ophthalmoscopy reveals yellowish-white foci of leukemic infiltration on the retina, as well as pronounced foci of hemorrhage.

Leukemic skin infiltration observed more often in patients with acute myeloid leukemia and rarely in patients with acute lymphoblastic leukemia. Leukemic skin lesions look like dense, diffuse, slightly protruding formations of various colors above the skin - from dark brown to red, sometimes they are nodular formations. Leukemic skin infiltrates are located on different areas body, sometimes they are found on the scalp, in the projection of the ribs, pelvic bones. Cutaneous leukemias can be accompanied by intense itching. The listed clinical syndromes characterize the period of extensive clinical and hematological manifestations of acute leukemia in children.

During the terminal period of leukemia General symptoms associated with deep, irreversible changes in life come to the fore. important organs, with the loss of the immunological properties of the body. Patients are in a state of severe toxicosis, adynamic, drowsy, sometimes apathy is replaced by excitement, delusions and hallucinations occur. Children are reluctant to make contact, some show aggressiveness. All children experience a sharp decrease in appetite up to complete anorexia, vomiting, often with blood, and increasing exhaustion.

Signs of cardiovascular failure appear: shortness of breath, pastiness, often on the face and lower limbs, sometimes swelling, displacement of the borders of the heart, dullness of heart sounds, the presence of systolic murmur over the entire area of ​​the heart, gallop rhythm, arrhythmia. The pulse is weak, frequent, small. Blood pressure is often reduced, venous pressure is increased. All children have severe pallor of the skin and mucous membranes, there is a hemorrhagic syndrome, in most of them it is pronounced, which is manifested by hemorrhages in the skin, mucous membranes, prolonged nasal and gingival bleeding. In some cases, hematuria is observed, gastrointestinal bleeding, cerebral hemorrhages. Peripheral lymph nodes are usually enlarged. Osteoarticular and abdominal pain intensifies. There is an enlargement of the liver and spleen. Much more often than during the period of full development of the disease, necrotic lesions of the skin and mucous membranes appear. A secondary infection occurs with the development of severe complications of a septic nature; pneumonia is quite common, which actually completes the leukemic process.

Laboratory data and instrumental studies.

General blood analysis - the most important method research. Main changes general analysis blood in acute leukemia are:

- anemia - a characteristic sign of acute leukemia, caused by a decrease in the production of red blood cells due to the replacement of the normal erythroid sprout with leukemic cells, bleeding. The anemia is usually normochromic, normocytic;

- reticulocytopenia;

- thrombocytopenia, platelet count is rarely normal;

- change in the total number of leukocytes - a significant increase in the number of leukocytes (more than 100 x 10 9 / l, leukemic form of leukemia) is observed in 15-20% of patients with acute leukemia due to leukemic cells; in other patients, the number of leukocytes in the peripheral blood may be slightly increased (subleukemic form) or even reduced (alukemic form). Thus, with the aleukemic form of leukemia, pancytopenia syndrome (anemia, leukopenia, thrombocytopenia) is observed;

- appearance of blasts in peripheral blood. Blast cells in almost all forms of acute leukemia look like large cells, with a large nucleus (it occupies almost the entire cell), which is distinguished by a delicate mesh structure of chromatin with large single nuclei. The cytoplasm of the blasts is represented by a narrow rim of bluish or bluish-grayish color with single small granules or without granules. It should be emphasized here that, as A.I. Vorobyov points out, “it is absolutely mandatory for diagnosis to establish the classical structure of the nucleus of blast cells: soft-chromatin-fine mesh with uniform color and caliber of chromatin threads.” In the leukemic form of acute leukemia, the number of blasts in the peripheral blood can be large (from 5-6 to 80-90%), in the aleukemic form the number of blasts is small or absent;

- decrease in the number of mature neutrophils;

- the phenomenon of "failure"(“leukemic gaping”) - the absence (loss) of intermediate forms between blast cells and mature neutrophilic granulocytes, i.e. practically complete absence young, band leukocytes and a small number of segmented leukocytes. In some cases, young cells may appear in the peripheral blood, but more mature than blasts (for example, promyelocytes), but their number, as well as the number of more mature cells following them, is small and the “failure” phenomenon persists;

- disappearance of eosinophils and basophils;

- increase in ESR.

Bone marrow punctate analysis(myelogram) - is mandatory in making a diagnosis of acute leukemia. It should be emphasized that the content of blast cells in the bone marrow is a decisive sign in the diagnosis of the disease. Acute leukemia is characterized by the following myelogram data:

- the number of blasts ranges from 25% to total replacement of bone marrow by the tumor. At the same time, anaplasia of blast cells can be observed - the presence of folding, depressions, fragmentation, vacuolization of the nucleus. If the number of blasts does not exceed 20%, they speak of low-percentage leukemia;

Neuroleukemia is a complication manifested in damage to the central nervous system and peripheral nervous system by metastases in leukemia, acute and chronic lymphoblastic, as well as myeloblastic, leading to serious consequences.

In neuroleukemia, the meninges may be involved in the process, which is characterized by symptoms such as repeated vomiting and nausea, headache with stiff neck muscles, epileptic seizures and depression of consciousness, drowsiness and behavior inappropriate to the situation.

Neuroleukemia amazes nervous system, central and peripheral, meninges, with their diffuse infiltration a complication may occur - hydrocephalus. Neuroleukemia is Compression or infiltration of leukemic deposits of cranial nerves and spinal nerve roots is also diagnosed by examining the cerebrospinal fluid, which reveals leukemic cells, a decreased level of glucose and an increased level of protein. In addition to hydrocephalus, with diffuse infiltration of the meninges, strabismus and nystagmus are observed, the optic discs swell, and in the analysis of cerebrospinal fluid, cellular elements are found to be normal.

Leukemic deposits can form sites in every part of the central nervous system, and the accumulations affect cranial nerves, causing hemiplegia, hemianopsia, aphasia, cortical blindness, and seizures. Neuroleukemia - what is it?, and this, in addition to seizures, also causes blindness, since infiltration can also affect the optic nerve, numbness of the chin is possible, when the mental nerve is affected, ulcers appear on the oral mucosa, but they are painless. The hypothalamus, with diffuse infiltration, causes neuroendocrine disorders in addition to hydrocephalus, the sleep-wake pattern is disrupted, hyperphagia appears, it is accompanied by vomiting and obesity, as a result, aggression and headache.

When the nerves of the skull are damaged, the patient has double vision, the movement of the eyeballs is impaired, the level of vision on the affected side decreases, up to complete blindness, atrophy of the optic disc develops, and the facial nerve may be affected with slight paralysis of the facial muscles.

If there are no clinical manifestations of neuroleukemia, this does not mean that there is no leukemic lesion of the meninges; in half of the patients with no signs, this can be detected by CT or EEG; lesions of the medulla will be visible.

With neuroleukemia, meningeal and hypertensive syndrome manifests itself, and if neuroleukemia affects the bone marrow substance, the patient develops convulsions, he perceives reality poorly, and seizures are observed. When neuroleukemia begins, a high level of cytosis and a large number of blast cells are detected in the cerebrospinal fluid; if metastases have penetrated into the brain, blastocytosis is absent. Problems in the field of neurology appear in approximately 3% of patients with leukemia; they are caused by infections, treatment with medications or radiotherapy, hemorrhages, improper circulation due to high blood viscosity, and infiltration by pathogenic cells.

Paralysis may occur with neuroleukemia oculomotor nerve, while the pupil reactions persist, the eye discs swell, it is necessary to select treatment. It depends on the likelihood of developing various symptoms, is quite complex, and usually consists of an endolumbar injection of methotrexate and cytarabine until the symptoms disappear and cerebrospinal fluid laboratory values ​​return to normal. It is necessary to sanitize the cerebrospinal fluid, and pay the closest attention to this, because if leukemia begins a subclinical course, a relapse will occur, which is more difficult to combat.

In addition to the intralumbar administration of metatrexate, it is necessary to carry out radiotherapy, in which the head is irradiated at a dose of 2400 rad; if the lesions are localized in other tissues, not bone marrow, other organs are irradiated. If leukemic foci are present, for example, in the lymph nodes of the mediastinum, testicles, nasopharynx, which compress the organs, causing pain, radiation therapy is carried out locally.

Clinical manifestations of neuroleukemia in chronic lymphoblastic leukemia are the same as in acute ones, and they depend on the location of the lesion, when in addition to infiltration of the meninges, the substance of the brain and cranial nerves are affected.

You can suspect neuroleukemia in a patient with leukemia based on a number of signs: the patient complains of headache, nausea and vomiting, he becomes irritable, his face may warp due to the disorder cerebral circulation, hearing and vision decrease or disappear altogether.