Lymphocytic leukemia causes. How does B-cell chronic lymphocytic leukemia manifest? Chronic lymphocytic leukemia: treatment

A disease known as chronic lymphocytic or B-cell leukemia is oncological process, associated with the accumulation of atypical B-lymphocytes in the blood, lymph and lymph nodes, bone marrow, . It is the most common disease from the group of leukemias.

It is believed that B-cell chronic lymphocytic leukemia mainly affects Europeans at a fairly old age. Men suffer from this disease much more often than women - in them this form of leukemia occurs 1.5-2 times more often.

Interestingly, this disease practically does not occur among representatives of Asian nationalities living in Southeast Asia. The reasons for this feature and why people from these countries differ so much in this moment still not installed.In Europe and America, among the white population, the incidence rate per year is 3 cases per 100,000 population.

The full causes of the disease are unknown.

A large number of cases are registered in representatives of the same family, which suggests that the disease is inherited and is associated with genetic disorders.

The dependence of the onset of disease on exposure or harmful influence environmental pollution, the negative effects of hazardous production or other factors have not yet been proven.

Symptoms of the disease

Externally, B-cell chronic lymphocytic leukemia may not appear for a very long time, or its signs are simply not paid attention to due to blurring and lack of expression.

Main symptoms of the pathology:

Typically, from external signs, patients note an unmotivated loss of body weight with a normal, healthy and sufficiently high-calorie diet. There may also be complaints about heavy sweating, which appears literally with the slightest effort.
Next, symptoms of asthenia appear - weakness, lethargy, fatigue, lack of interest in life, disturbances in sleep and normal behavior, inappropriate reactions and behavior.
The next sign to which sick people usually react is an increase lymph nodes. They can be very large, compacted, consisting of groups of nodes. To the touch, enlarged nodes may be soft or dense, but compression of the internal organs is usually not observed.
At later stages, an increase occurs and the growth of the organ is felt, described as a feeling of heaviness and discomfort. In the final stages, general weakness, dizziness, and sudden symptoms develop, appear, and increase.

Patients with this form of lymphocytic leukemia have very depressed immunity, so they are especially susceptible to a variety of colds and infectious diseases. For the same reason, diseases are usually difficult, they are protracted and difficult to treat.

Among the objective indicators that can be recorded in the early stages of the disease is leukocytosis. Only by this indicator, coupled with a complete medical history, can a doctor detect the first signs of the disease and begin to treat it.

Possible complications

For the most part, B-cell chronic lymphocytic leukemia proceeds very slowly and has almost no effect on life expectancy in elderly patients. In some situations, there is a fairly rapid progression of the disease, which has to be restrained by the use of not only medicines, but also by radiation.

Basically, the threat is posed by complications caused by a severe weakening of the immune system. In this condition, any cold or mild infection can cause a very serious illness. Such diseases are very difficult to bear. Unlike a healthy person, a patient suffering from cellular lymphocytic leukemia is very susceptible to any cold, which can develop very quickly, be severe and cause severe complications.

Even a mild runny nose can be dangerous. Due to weak immunity, the disease can quickly progress and be complicated by sinusitis, otitis media, bronchitis, and other diseases. Pneumonia is especially dangerous; it greatly weakens the patient and can cause his death.

Methods for diagnosing the disease

The definition of a disease is based on external signs and does not provide complete information. Bone marrow is also rarely performed.

The main methods for diagnosing the disease are the following:

Carrying out a specific blood test (immunophenotyping of lymphocytes).
Performing a cytogenetic study.
Study of a biopsy of bone marrow, lymph nodes, etc.
Sternal puncture or myelogram study.

Based on the results of the examination, the stage of the disease is determined. The choice of a specific type of treatment, as well as the patient’s life expectancy, depends on it. According to modern data, the disease is divided into three periods:

Stage A - complete absence of lymph node involvement or the presence of no more than 2 affected lymph nodes. Absence of anemia and thrombocytopenia.
Stage B - in the absence of thrombocytopenia and anemia, there are 2 or more affected lymph nodes.
Stage C - thrombocytopenia and anemia are registered, regardless of whether lymph nodes are affected or not, as well as the number of nodes affected.

Treatment method for chronic lymphocytic leukemia

According to many modern doctors, B-cell chronic lymphocytic leukemia in the initial stages does not require specific treatment due to mild symptoms and low impact on the patient’s well-being.

Intensive treatment begins only in cases where the disease begins to progress and affects the patient’s condition:

With a sharp increase in the number and size of the affected lymph nodes.
With enlarged liver and spleen.
If diagnosed fast growth numbers.
With increasing signs of thrombocytopenia and anemia.

If the patient begins to suffer from manifestations of cancer intoxication. This usually manifests itself as rapid, unexplained weight loss, severe weakness, the appearance febrile conditions and night sweats.

The main method of treating the disease is chemotherapy.

Until recently, the main drug used was Chlorbutin; at the moment, Fludara and Cyclophosphamide, intensive cytostatic agents, are successfully used against this form of lymphocytic leukemia.

A good way to influence the disease is to use bioimmunotherapy. It uses monoclonal antibodies, which allows you to selectively destroy cancer-affected cells while leaving healthy cells untouched. This technique is progressive and can improve the quality and life expectancy of the patient.

More information about leukemia can be found in the video:

If all other methods have not shown the expected results and the disease continues to progress, the patient becomes worse, there is no other choice but to use high doses active “chemistry” followed by the transfer of hematopoietic cells.

In those difficult cases where the patient suffers from severely enlarged lymph nodes or there are many of them, the use of radiation therapy may be indicated.When the spleen enlarges sharply, becomes painful and does not actually perform its functions, it is recommended to remove it.

Despite the fact that B-cell chronic lymphocytic leukemia is an oncological disease, you can live with it long years, maintaining normal body functions and fully enjoying life. But for this you need to take certain measures:

You need to take care of your health and seek medical care when the slightest suspicious symptoms appear. This will help identify the disease in the early stages and prevent its spontaneous and uncontrolled development.
Since the disease greatly affects work immune system sick, he needs to protect himself as much as possible from colds and infections of any kind. If there is infection or contact with sick people or sources of infection, the doctor may prescribe the use of antibiotics.
To protect their health, a person needs to avoid potential sources of infection and places with large crowds of people, especially during periods of mass epidemics.
The living environment is also important - the room must be cleaned regularly, the patient needs to monitor the cleanliness of his body, clothes and bed linen, as all of these can be sources of infection. .
Patients with this disease should not be in the sun, trying to protect themselves from its harmful effects.
Also, to maintain immunity, proper balanced diet with an abundance of plant foods and vitamins, refusal bad habits and moderate physical activity, mainly in the form of walking, swimming, and light gymnastics.

A patient with such a diagnosis must understand that his disease is not a death sentence, that one can live with it for many years, maintaining good spirits and body, clarity of mind and a high level of performance.

Lymphocytic leukemia is a malignant lesion that arises in the lymphatic tissue. It is characterized by the accumulation of tumor lymphocytes in the lymph nodes, in the peripheral blood and in the bone marrow. The acute form of lymphocytic leukemia has recently been classified as a “childhood” disease due to its susceptibility mainly to patients aged two to four years. Today, lymphocytic leukemia, the symptoms of which are characterized by their own specificity, is observed more often among adults.

general description

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

As for lymphocytic leukemia specifically, it, as we have already noted, is malignant disease, while the growth lymphoid tissue occurs in the lymph nodes, bone marrow, liver, spleen, and some other types of organs. The pathology is predominantly diagnosed in the Caucasian race, with about three cases of the disease occurring annually for every hundred thousand people. The disease mainly affects older people, with males being twice as likely to suffer from lymphocytic leukemia than females. In addition, predisposition to the disease is also determined by the influence of hereditary factors.

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

Acute lymphocytic leukemia: symptoms

To diagnose this form of the disease, peripheral blood is used, in which characteristic blasts are found in about 98% of the total number of cases. The blood smear is characterized by a “leukemic gap” (or “gap”), that is, only mature cells and blasts are present, with no intermediate stages. The acute form of lymphocytic leukemia is characterized by normochromic anemia, as well as. Somewhat less common are other signs of the acute form of lymphocytic leukemia, namely leukopenia and leukocytosis.

In some cases, consideration of the general blood picture in combination with symptoms suggests the relevance of acute lymphocytic leukemia, but diagnostic accuracy is only possible when conducting a study involving the bone marrow, in particular to characterize its blasts histologically, cytogenetically and cytochemically.

The main symptoms of the acute form of leukocytosis are the following:

Patients complain of general malaise, weakness;
Loss of appetite;
Change (loss) in weight;
Unmotivated temperature rise;
Anemia, causing pale skin;
Shortness of breath, cough (dry);
Stomach ache;
Nausea;
Headache;
A state of general intoxication in a wide variety of manifestations. Intoxication defines a type of condition in which a disruption of the normal functioning of the body occurs due to the penetration or formation of toxic substances in it. In other words, this is a general poisoning of the body, and depending on the degree of its damage against this background, symptoms of intoxication are determined, which, as noted, can be very different: nausea and vomiting, headache, diarrhea, abdominal pain - disorders of the gastrointestinal tract; symptoms of the disorder heart rate(arrhythmia, tachycardia, etc.); symptoms of central dysfunction nervous system(dizziness, depression, hallucinations, impaired visual acuity), etc. ;
Painful sensations in the area of the spine and limbs;
Irritability;
An increase in peripheral lymph nodes during the development of the disease. In some cases - mediastinal lymph nodes. Mediastinal lymph nodes, in turn, are divided into 4 main groups: regional lymph nodes superior mediastinum to the bifurcation of the trachea; retrosternal lymph nodes (in the area behind the sternum); bifurcation lymph nodes (lymph nodes of the lower tracheobroncheal region); lymph nodes of the inferior posterior mediastinum;
About half of the total number of cases of the disease is characterized by the development hemorrhagic syndrome with its characteristic hemorrhages - these are petechiae. Petechiae are small-type hemorrhages, focusing mainly on the skin, in some cases on the mucous membranes; their sizes can vary, from a pinhead to the size of a pea;
The formation of foci of extramedullary lesions in the central nervous system provokes the development of neuroleukemia;
In rare cases, infiltration of the testicles occurs - such a lesion in which they increase in size, predominantly such an increase is unilateral (accordingly, the occurrence of leukemic nature is diagnosed in approximately 1-3% of cases).

Chronic lymphocytic leukemia: symptoms

In this case we're talking about about an oncological disease of the lymphatic tissue, for which a characteristic manifestation is the accumulation of tumor lymphocytes in the peripheral blood. When compared with the acute form of lymphocytic leukemia, it can be noted that the chronic form is characterized by a slower course. As for hematopoietic disorders, they occur only at a late stage of the disease.

Modern oncologists use several types of approaches that make it possible to determine the accuracy of compliance with a specific stage of chronic lymphocytic leukemia. Life expectancy among patients suffering from this disease depends directly on two factors. In particular, these include the degree of disruption of the hematopoietic process in the bone marrow and the degree of prevalence that is characteristic of malignant neoplasm. Chronic lymphocytic leukemia, in accordance with general symptoms, is divided into the following stages:

Initial stage (A). It is characterized by a slight increase in the area of the lymph nodes of one or two groups. Over a long period of time, the trend in blood leukocytosis does not increase. Patients remain under medical supervision, without the need for cytostatic therapy. Thrombocytopenia and anemia were absent.
Expanded stage (B). In this case, leukocytosis takes on an increasing form, the lymph nodes increase on a progressive or generalized scale. Recurrent infections occur. For the advanced stage of the disease, appropriate active therapy is required. Thrombocytopenia and anemia are also absent.
Terminal stage (C). This includes cases in which malignant transformation of the chronic form of leukocytosis occurs. Thrombocytopenia occurs, regardless of the susceptibility to damage to a particular group of lymph nodes.

The letter designation is often displayed using Roman numerals, which also determine the specificity of the disease and the presence of certain symptoms in the patient in a particular case:

I – in this case, the number indicates the presence of lymphadenopathy (that is, enlarged lymph nodes);
II – an indication of an increase in the size of the spleen;
III – indication of the presence of anemia;
IV – indication of the presence of thrombocytopenia.

Let us dwell in more detail on the main symptoms that characterize chronic lymphocytic leukemia. Here the following manifestations become relevant, the development of which is gradual and slow:

General weakness and malaise (asthenia);
A feeling of heaviness that occurs in the abdomen (especially from the left hypochondrium);
Sharp weight loss;
Enlarged lymph nodes;
Increased susceptibility to various types of infections;
Excessive sweating;
Decreased appetite;
Enlarged liver (hepatomegaly);
Enlarged spleen (splenomegaly);
Anemia;
Thrombocytopenia (a symptom that is characterized by a decrease in the concentration of platelets in the blood below a certain norm);
Neutropenia. In this case, we mean a symptom characterized by a decrease in neutrophil granulocytes in the blood. Neutropenia, which in this case acts as a symptom of the underlying disease (lymphocytic leukemia itself), is a disease accompanied by a change (decrease) in the number of neutrophils (neutrophilic granulocytes) in the blood. Neutrophils in particular are blood cells that mature in the bone marrow over a period of two weeks. Due to these cells, the subsequent destruction of foreign agents that may be in the circulatory system occurs. Thus, against the background of a decrease in the number of neutrophils in the blood, our body becomes more susceptible to the development of certain infectious diseases. Similarly, this symptom is associated with lymphocytic leukemia;
The occurrence of frequently occurring allergic reactions.

Chronic lymphocytic leukemia: forms of the disease

Morphological and clinical signs of the disease are determined by detailed classification chronic lymphocytic leukemia, which also indicates an appropriate response regarding the treatment performed. The main forms of chronic lymphocytic leukemia include:

Benign form;
Classic (progressive) form;
Tumor form;
Splenomegalic form (with enlarged spleen);
Bone marrow form;
A form of chronic lymphocytic leukemia with a complication in the form of cytolysis;
Prolymphocytic form;
Hairy cell leukemia;
T cell form.

Benign form. It provokes a slow and noticeable only over the years increase in lymphocytosis in the blood, which is also accompanied by an increase in the number of leukocytes in it. It is noteworthy that in this form the disease can last for a considerable time, up to decades. Working capacity is not impaired. In most cases, while patients are under observation, sternal puncture and histological examination of lymph nodes are not performed. These studies have a significant impact on the psyche, while neither they nor cytostatic medications may, due to such features of the course of the disease, be needed at all for the rest of the patient’s life.

Classic (progressive) form. It begins in a similar way to the previous form, however, the number of leukocytes increases from month to month, and the growth of lymph nodes is also observed, which in consistency can be dough-like, slightly elastic and soft. Cytostatic therapy is prescribed in the case of a noticeable increase in the manifestations of the disease, as well as in the case of lymph node growth and leukocytosis.

Tumor form. The peculiarity here is the significant increase in the consistency and density of the lymph nodes, while leukocytosis is low. There is an increase in the tonsils almost to the point of their closure with each other. The spleen increases to moderate levels, in some cases the increase can be significant, up to a protrusion within a few centimeters in the hypochondrium. Intoxication in this case is of a mild nature.

Bone marrow form. It is characterized by rapidly progressing pancytopenia, partial or total replacement by mature lymphocytes in their diffusely growing bone marrow stage. No enlargement of the lymph nodes is observed; in the vast majority of cases, the spleen does not undergo enlargement, nor does the liver. Concerning morphological changes, then they are characterized by the homogeneity of the structure that nuclear chromatin acquires; in some cases, pictonicity is observed in it; structural elements are rarely determined. It is noteworthy that earlier this form led to death, with a life expectancy of up to 2 years with the disease.

Prolymphocytic form. The difference lies primarily in the morphology of lymphocytes. Clinical features are characterized by the rapid development of this form with a significant increase in the spleen, as well as a moderate increase in peripheral lymph nodes.

Chronic lymphocytic leukemia with paraproteinemia. The clinical picture has the usual features of the forms listed above, accompanied by monoclonal gammopathy type G- or M-.

Hairy cell form. In this case, the name determines the structural features of lymphocytes, which represent the development of the process of chronic lymphocytic leukemia in this form. The clinical picture has characteristic features, which consist of cytopenia in one form or another (moderate/severe). The spleen is enlarged, the lymph nodes have normal sizes. The course of the disease in this form is different, up to a complete absence of signs of progression during for long years. Granulocytopenia is observed, in some cases provoking the occurrence of fatal complications of an infectious nature, as well as thrombocytopenia, characterized by the presence of hemorrhagic syndrome.

T-shape. This form accounts for about 5% of cases of the disease. Infiltration primarily affects the skin tissue and deep layers of the dermis. The blood is characterized by leukocytosis in varying degrees its severity, neutropenia and anemia occur.

Lymphocytic leukemia: treatment of the disease

The peculiarity of the treatment of lymphocytic leukemia is that experts agree that it is inappropriate to carry it out at an early stage. This is due to the fact that most patients, during the initial stages of the disease, experience it in a “smoldering” form. Respectively, long time you can do without the need for an appointment medicines, and also live without any restrictions, while being in relatively good condition.

Therapy is carried out for chronic lymphocytic leukemia, and only if there is a reason for this in the form of characteristic and striking manifestations of the disease. Thus, the feasibility of treatment arises if there is a rapid increase in the number of lymphocytes, as well as with the progression of lymph node enlargement, rapid and significant enlargement of the spleen, increasing anemia and thrombocytopenia.

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

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

If there is no required effect in using these methods, the doctor prescribes high-dose chemotherapy, which involves subsequent transplantation of hematopoietic stem cells. If the patient has a significant tumor mass, it is used radiation therapy, acting as an adjuvant therapy in treatment.

Severe enlargement of the spleen may require complete removal of this body.

Diagnosing the disease requires contacting specialists such as a therapist and hematologist.

The main external signs of chronic lymphocytic leukemia - lymphatic leukocytosis and enlargement of the lymph nodes, and later the spleen and liver - are caused by the proliferation of lymphocytes.

Since the tumor process in chronic lymphocytic leukemia involves different cases different clones of lymphocytes; strictly speaking, the nosological form of “chronic lymphocytic leukemia” should consist of many diseases, although they have a number of common features. Already cellular analysis of chronic lymphocytic leukemia reveals a variety of cellular variants: the predominance of narrow-plasma or, on the contrary, wide-plasma forms, cells with younger or roughly pyknotic nuclei, with clearly basophilic or almost colorless cytoplasm.

Clones of lymphocytes with an aberrant set of chromosomes were obtained in T-forms using the action of PHA on lymphocytes as a mitogen. In B-lymphocytic leukemia, in order to induce division of lymphocytes, exposure to polyvalent mitogens was required: Epstein-Barr virus, lipopolysaccharide from E.coli. Karyological data prove not only clonality, but also the mutational nature of chronic lymphocytic leukemia and the appearance of subclones as the process develops, as can be judged by the evolution of chromosomal changes in individual cases.

It has been proven that the majority of leukemic B-lymphocytes in chronic lymphocytic leukemia contain monoclonal cytoplasmic immunoglobulin, or rather, an immunoglobulin heavy chain. The monoclonality of cytoplasmic immunoglobulin is easier to prove than that of surface immunoglobulin. The detection of cytoplasmic immunoglobulin in B-lymphocytes of chronic lymphocytic leukemia confirms the assumption that these lymphocytes represent cells of one of the early stages of B-lymphocyte differentiation, and makes clear the low content of immunoglobulins on their surface.

Cytopenia in chronic lymphocytic leukemia can be of different nature. Although chronic lymphocytic leukemia most often originates from B-lymphocyte precursor cells, it may increase the content of T-suppressor cells in the blood and spleen. An increased content of these cells, non-tumoral in nature, can lead to suppression of the proliferation of hematopoietic precursor cells, in particular BFU-E, granulocyte-macrophage progenitor cell - CFU-GM, and possibly common cell- precursors of myelopoiesis.

Another genesis of cytopenia in chronic lymphocytic leukemia is autoimmune, associated with the formation of antibodies to hematopoietic cells, to maturing bone marrow cells or to mature elements of the blood and bone marrow. The autoimmune nature of the destruction of erythrocytes in chronic lymphocytic leukemia is proven by the appearance of a positive direct Coombs test, and the destruction itself is evidenced by reticulocytosis in the blood, an increased content of erythrokaryocytes in the bone marrow, a reduction in the lifespan of erythrocytes, and bilirubinemia. If anemia is not accompanied by reticulocytosis, and there is an increased content of erythrokaryocytes in the bone marrow and there is indirect bilirubinemia, then intramedullary lysis of erythrokaryocytes can be assumed. The immune nature of anemia is proven in these cases by a positive aggregate hemagglutination test.

In addition, the cytolytic process can be caused by leukemia cells themselves, if they functionally have killer properties.

Symptoms of Chronic Lymphocytic Leukemia

For many years, only lymphocytosis may be observed - 40-50%, although the total number of leukocytes fluctuates around the upper limit of normal. Lymph nodes may be normal in size, but they become enlarged with various infections, and after the elimination of the inflammatory process they are reduced to the original value.

Lymph nodes gradually enlarge, usually first of all in the neck, in the armpits, then the process spreads to the mediastinum, abdominal cavity, and groin area. Nonspecific phenomena common to all leukemia occur: increased fatigue, weakness, sweating. On early stages In most cases, anemia and thrombocytopenia do not develop.

Lymphocytosis in the blood gradually increases; 80-90% of lymphocytes, as a rule, are observed when the bone marrow is almost completely replaced by lymphocytes. The spread of lymphatic tissue in the bone marrow may not inhibit the production of normal cells for years. Even when high numbers of leukocytes in the blood are reached, 100,000 in 1 μl or more, there is often no anemia, the platelet count is normal or slightly reduced.

Bone marrow studies show an increase in the content of lymphocytes in the myelogram - usually more than 30%, and characteristic proliferations of lymphoid cells, often diffuse, are also noted.

The structure of lymphocytes in chronic lymphocytic leukemia does not have stable and typical features. It can change during the course of the disease under the influence of viral infections. Unlike other leukemias, the predominance in the blood of cells with the same name (in this case, lymphocytes) does not mean the predominance of leukemic cells, since both B-lymphocytes of the leukemic clone and an increased number of polyclonal T-lymphocytes are often simultaneously present in the circulation. In the blood, the majority of cells are mature lymphocytes, no different from normal ones. Along with such cells, there may be lymphocytic elements with a more homogeneous nucleus, which do not yet have the rough lumpiness of the chromatin of a mature lymphocyte, with a wide rim of cytoplasm, which sometimes, as in infectious mononucleosis, has perinuclear clearing. Cell nuclei may have a peculiar twisted loop or be regularly round; bean-shaped kernels are also found; the cytoplasm has fragmentary contours, sometimes with elements of “hairiness,” but without the histochemical features of hairy cell leukemia.

A characteristic sign of chronic lymphocytic leukemia is dilapidated nuclei of lymphocytes - Humnrecht's shadows. Their number does not indicate the severity of the process.

At the onset of the disease, prolymphocytes and lymphocytes in leukocyte formula usually not.

On this basis, a prolymphocytic form of chronic lymphocytic leukemia is isolated. Sometimes such leukemia can occur with the secretion of monoclonal immunoglobulin.

As the disease progresses, single prolymphocytes and lymphoblasts begin to appear in the blood. A large number of them appear only in the terminal stage of the disease.

Stages of chronic lymphocytic leukemia. At the initial stage of the process, there is a slight increase in several lymph nodes of one or two groups, leukocytosis does not exceed 30 × 103 - 50 × 103 in 1 μl and, most importantly, over the course of months there is no tendency to a noticeable increase. At this stage, patients remain under the supervision of a hematologist, and cytostatic therapy is not carried out. The advanced stage is characterized by increasing leukocytosis, progressive or generalized enlargement of lymph nodes, the appearance of recurrent infections, and autoimmune cytopenias. This stage requires active therapy. The terminal stage includes cases of malignant transformation of chronic lymphocytic leukemia.

Diagnosis of chronic lymphocytic leukemia is not difficult. The criteria are as follows: absolute lymphocytosis in the blood, more than 30% of lymphocytes in the bone marrow aspirate with diffuse lymphatic hyperplasia in the bone marrow trephine. Enlargement of the lymph nodes and spleen is an optional sign of chronic lymphocytic leukemia, but when involved in the process, diffuse proliferation of lymphocytes is observed in these organs. Auxiliary diagnostic sign lymphatic tumor proliferation are Gumprecht's shadows in the blood smear.

Chronic lymphocytic leukemia must be differentiated from another mature cell lymphocytic tumor process - lymphocytoma. It is distinguished from lymphocytoma by the predominant localization of lymphatic proliferation in the bone marrow and its diffuse nature in this organ, as well as in others involved in the process, confirmed by histological examination.

Complications

All 3 commonly tested immunoglobulins (A, G and M) or some of them may be reduced. In secreting lymphoproliferative processes, along with an increase in monoclonal immunoglobulin, the level of normal immunoglobulins. In doubtful diagnostic situations, with low lymphocytosis, a decrease in the level of normal immunoglobulins can serve as an argument in favor of the lymphoproliferative process. At the same time, a typical picture is possible when normal level y-globulins and immunoglobulins in blood serum. Hypogammaglobulinemia is not associated with the duration of the disease and the severity of lymphocytosis. It may be caused by a violation of the interaction between T and B lymphocytes, an increased content of T suppressor cells, and the inability of leukemic B lymphocytes to respond to lymphokines produced by normal T lymphocytes.

Increased sensitivity to infection in patients with chronic lymphocytic leukemia is one of the the most important factors leading to death. The reasons for this susceptibility are not entirely clear and there appear to be several. According to E.G. Bragina, the tendency to infectious complications is not always parallel to hypogammaglobulinemia; it can also occur with a normal level of γ-globulins in the serum. Frequent infectious complications do not always parallel the increase in leukocytosis.

The incidence of pneumonia, especially in chronic lymphocytic leukemia, is facilitated by lymphatic infiltration of the lung tissue itself, an increase in the lymphatic follicles of the bronchial tree, leading to collapse of all or part of the lung, disruption of pulmonary ventilation and drainage function of the bronchi. Typically, these phenomena increase as the disease progresses. Frequent complications there are inflammatory processes in fiber, caused by staphylococcus or gram-negative bacteria.

At the same time, increased susceptibility to infection, which is defined by the term “infectiousness,” in the initial stage of the process is apparently associated with defects in the immune response and disturbances in the interaction of T- and B-lymphocytes. Insufficient courses may contribute to the recurrence and protracted course of infections

antibiotic therapy. In specialized hematology and oncology hospitals, where patients with severe immunosuppression accumulate and new pathogenic strains of pathogens appear, peculiar “epidemics” very often break out.

More often, patients suffer from herpes zoster ( herpes zoster). It can be both typical and generalized, causing complete skin damage, while a local segmental rash of blisters quickly becomes confluent. Herpetic rashes can also invade the mucous membranes of the digestive tract and bronchi. The same lesion occurs with herpes simplex (herpes simplex), chicken pox.

Patients with chronic lymphocytic leukemia often experience severe infiltration at the site of mosquito bites; With multiple bites, severe intoxication is possible.

Immune complex complications of chronic lymphocytic leukemia and other lymphoproliferative diseases are rare. They can be expressed by Senlein-Henoch syndrome, polyneuritis.

In chronic lymphocytic leukemia, there is often infiltration of the VIII pair of cranial nerves with weakened hearing, a feeling of “stuffiness,” and tinnitus. As with other leukemias, the development of neuroleukemia is possible; as a rule, this is a terminal exacerbation when the meninges are infiltrated by young lymphoid cells. The clinical picture of neuroleukemia does not differ from that of acute leukemia; in the meninges, the process was eliminated by intralumbar administration of cytosar with methotrexate. Simultaneously with infiltration meninges Infiltration of brain matter may occur, the treatment of which requires irradiation. Radicular syndrome, caused by lymphatic infiltration of the roots, usually occurs in the terminal stage of the disease.

One of the severe manifestations of chronic lymphocytic leukemia is exudative pleurisy. Its nature can be different: para- or metapneumonic pleurisy with a banal infection, tuberculous pleurisy, lymphatic infiltration of the pleura, compression or rupture of the thoracic lymphatic duct. With pleurisy infectious origin in the exudate, along with lymphocytes, there are many neutrophils. With infiltration of the pleura, compression and rupture of the lymphatic duct, the exudate will be lymphatic, but if the fluid comes from the duct, it will contain a large amount of fat (chylous fluid).

Active treatment must be timely, since forced repeated removal of pleural exudate quite quickly leads to exhaustion and hypoalbuminemic edema. When breaking thoracic duct surgical restoration of its integrity is indicated.

Patients die mainly due to severe infectious complications, increasing exhaustion, bleeding, anemia, sarcoma growth.

As a rule, with chronic lymphocytic leukemia there is no qualitative change in the behavior of tumor cells for a long time. There may be no signs of progression with the release of pathological cells from the control of cytostatic drugs throughout the entire disease.

If the process does enter the terminal stage, then it has the same symptoms as in other leukemias (suppression of normal hematopoietic germs, total replacement of bone marrow with blast cells).

The transition of chronic lymphocytic leukemia to the terminal stage is more often accompanied by sarcoma growth in the lymph node than by blast crisis. Such lymph nodes begin to grow rapidly, acquire a rocky density, infiltrate and compress neighboring tissues, causing swelling and pain that are not characteristic of the advanced stage of chronic lymphocytic leukemia. Often, sarcoma growth in the lymph nodes is accompanied by an increase in temperature. Sometimes such nodes are located in subcutaneous tissue face, torso, limbs, under the mucous membrane in the oral cavity, nose, and the vessels growing in them give them the appearance of hemorrhage; only the density and bulging of such a “hemorrhage” indicates its nature.

In the terminal stage, the beginning of which is sometimes impossible to determine, it is very difficult to decipher the sudden increase in temperature. It may be due to sarcoma transformation of the process; then sufficiently powerful cytostatic therapy should be used. With the same probability, with long-term chronic lymphocytopenia, an infection may occur, primarily tuberculosis (tuberculous infiltration of the lungs with granulocytopenia is not always detected x-ray). In these situations, determining the cause of the temperature increase takes a long time and requires the consistent use of bacteriostatic drugs.

One of the manifestations of the terminal stage of the disease can be severe renal failure due to infiltration of the organ parenchyma by tumor cells. A sudden cessation of urination should always lead the doctor to such an assumption. If all other causes of kidney damage are excluded, then kidney irradiation should be performed, which quickly eliminates impaired urination.

Treatment of Chronic Lymphocytic Leukemia

There has been no recovery from lymphocytic leukemia until recently. In some cases, complex chemotherapy provided long-term improvements. The life expectancy of patients varies widely - from several months to 2-3 decades.

Forms of chronic lymphocytic leukemia

The classification of chronic lymphocytic leukemia is based on morphological and clinical features, which also include response to treatment.

The following forms are distinguished:

1) benign;

2) progressive (classical);

3) tumor;

4) splenomegalic (enlarged spleen);

5) bone marrow;

6) chronic lymphocytic leukemia complicated by cytolysis;

7) prolymphocytic;

8) chronic lymphocytic leukemia occurring with paraproteinemia;

9) hairy cell leukemia;

10) T-cell.

Benign form of chronic lymphocytic leukemia causes a very slow increase in lymphocytosis in the blood, noticeable only over years, but not months, in parallel with an increase in the number of leukocytes. In the first stages, the lymph nodes are either not enlarged, or the cervical ones are enlarged very slightly. During infection, there is a high level of 2-3 H 104 (20-30 thousand) in 1 μl lymphatic leukocytosis, which disappears along with the infectious complication. A very slow increase in lymphocytosis to a noticeable enlargement of the lymph nodes can continue for years or decades. All this time, the patients are under dispensary observation, they are fully able to work, they are only prohibited from increased insolation. Blood tests with platelet and reticulocyte counts are done every 1-3 months. In the described form, until the deterioration of the condition may require treatment, in many cases a diagnostic sternal puncture is not performed. histological examination lymph node. These studies significantly traumatize the psyche of the patient, who often will not need cytostatic drugs until the end of his days.

Progressive (classical) form of chronic lymphocytic leukemia it begins in the same way as benign, but the number of leukocytes increases from month to month, as does the size of the lymph nodes. The consistency of the nodes can be doughy, soft or slightly elastic.

Cytostatic therapy for these patients is usually prescribed when there is a noticeable increase in all manifestations of the disease, leukocytosis and the size of the lymph nodes in the first place.

Tumor form of chronic lymphocytic leukemia. The peculiarity of this form, which determined its name, is the significant increase and dense consistency of the lymph nodes with low leukocytosis. The tonsils are enlarged and often almost close to each other. The enlargement of the spleen is usually moderate, but can also be significant; it often protrudes several centimeters from under the costal margin.

The leukocyte formula retains a sufficient percentage of neutrophils - 20% or more. The bone marrow usually contains no more than 20-40% lymphocytes, although it can be completely damaged.

Despite the significant hyperplasia of the lymphatic tissue, intoxication is poorly expressed for a long time, unlike generalized lymphosarcoma, with which this form of chronic lymphocytic leukemia is often confused.

Bone marrow form of chronic lymphocytic leukemialymphadenia ossium . Rapidly progressing pancytopenia, total or partial replacement of bone marrow by diffusely growing mature lymphocytes. The lymph nodes are not enlarged, the spleen, with very rare exceptions, is also not enlarged, and the liver is of normal size. Morphologically, the homogeneity of the structure of nuclear chromatin is noted, sometimes it is pyknotic, less often there are elements of structure that vaguely resemble blast; cytoplasm with pronounced basophilia, narrow, often fragmented. Previously, this form quickly led patients to death; life expectancy rarely exceeded 2 years (14-26 months).

The introduction of the VAMP regimen into the therapy of this form of the disease, as well as its further modernization, made it possible to achieve improvement and significantly prolong the life of patients.

Chronic lymphocytic leukemia, complicated by cytolysis, is not an independent form. It is possible that there is either a significant enlargement of the lymph nodes or the absence of lymphadenopathy; lymphatic leukocytosis may be very high, or the disease may proceed in the tumor subleukemic variant. The destruction of red blood cells is explained by reticulocytosis, an increase in the level of bilirubin and the percentage of red blood cells in the bone marrow, and immune form- positive direct Coombs test. Increased platelet dissolution is determined by thrombocytopenia, high or normal megakaryocytosis in the bone marrow.

It is much more difficult to determine the increased dissolution of granulocytes, since the content of their precursors in the bone marrow against the background of complete lymphatic proliferation cannot be determined. The increased breakdown of granulocytes can, with some degree of probability, be judged by their sudden disappearance from the peripheral blood.

In some cases, chronic lymphocytic leukemia, which occurs with cytolysis, is accompanied by a pronounced increase in temperature. The partial disappearance of any sprout in the bone marrow suggests intramedullary cytolysis.

Prolymphocytic form of chronic lymphocytic leukemia, as it is described in the literature (Volkova M. A.; Taylor et al), differs, first of all, in the morphology of lymphocytes, which in smears (blood and bone marrow), prints have a large, clear nucleolus; chromatin condensation in the nucleus, as shown by electron microscopy, is moderately expressed and mainly along the periphery. In histological preparations of lymph nodes and spleen in this form of leukemia, lymphocytes also contain nucleols. These cells have no cytochemical features. Immunological characteristics reveal either the B- or T-cell nature of lymphocytic leukemia, most often the former. Unlike the B-lymphocytes of typical chronic lymphocytic leukemia, in this form an abundance of immunoglobulins, usually M- or D-type, is found on the surface of leukemic lymphocytes.

The clinical features of this form are fast development, significant enlargement of the spleen and moderate enlargement of peripheral lymph nodes.

Chronic lymphocytic leukemia occurring with paraproteinemia, is characterized by the usual clinical picture of one of the previously listed forms of the process, but is accompanied by monoclonal M- or G-gammopathy.

Hairy cell form. The name of the form comes from the structural features of the lymphocytes representing it. These cells have a “youthful” nucleus: homogeneous, sometimes resembling the structural nucleus of blasts, sometimes remnants of nucleoli, often having an irregular shape and unclear contours. The cytoplasm of cells is diverse: it can be wide and have a scalloped edge, it can be fragmentary, not surrounding the cell along the entire perimeter, and it can have sprouts resembling hairs or villi. In some cases, the cytoplasm of lymphocytes in this form of chronic lymphocytic leukemia is basophilic, often grayish-blue. There is no granularity in the cytoplasm. Features of the structure of lymphocytes that make one suspect the hairy cell form of chronic lymphocytic leukemia are visible in light microscope, but in more detail - in a phase-contrast microscope and electron microscopy.

The diagnostic test that confirms the diagnosis of hairy cell leukemia is the cytochemical characterization of leukemic cells.

It is known that lymphocytes in this form of leukemia have some ability to absorb latex particles. These features of hairy cell leukemia cells make clear long-standing doubts about their lymphatic nature.

Immunological methods have shown that in most cases this is a B-cell form of chronic lymphocytic leukemia, although cases of hairy cell leukemia of a T-lymphocytic nature have been described. The original normal lymphocytes from which hairy cell leukemia originated are still unknown.

The clinical picture of hairy cell leukemia is quite characteristic: moderate to severe cytopenia, enlarged spleen, normal size of peripheral lymph nodes.

In bone marrow trephine, one can observe interstitial growth of leukemic cells, which, as a rule, do not form proliferates and do not completely displace hematopoietic tissue and fat. Histology of the spleen indicates a diffuse growth of leukemic lymphocytes in both the red and white pulp, erasing the structure of this organ.

The course of hairy cell leukemia varies. It, like other forms of chronic lymphocytic leukemia, may show no signs of progression for years. Granulocytopenia, which sometimes leads to fatal infectious complications, and thrombocytopenia with hemorrhagic syndrome are observed.

T-shape. Chronic lymphocytic leukemia, represented by T lymphocytes, occurs in approximately 5% of cases. Leukemic infiltration in this form of leukemia, unlike Sézary's disease, usually affects the deep layers of the dermis and skin tissue. The disease begins in people over 25 years of age.

The blood picture includes leukocytosis of varying severity, neutropenia, and anemia. Leukemic lymphocytes have large round, bean-shaped, polymorphic ugly nuclei, rough, often twisted chromatin; azurophilic granules, larger than the granules of ordinary lymphocytes, can be visible in the cytoplasm. Cell sizes vary.

Cytochemically, these cells can be detected high activity acid phosphatase (lysosomal nature), a-naphthyl acetate esterase, located locally in the cytoplasm. Immunologically, the lymphocytes that constitute the substrate of this form of leukemia, as shown by the study of their surface markers using monoclonal antibodies, can be T-helpers in some cases, T-suppressors in others, and helpers and suppressors in others.

Along with this rapidly progressing T-cell form of leukemia, a favorable form with large granular T-lymphocytes has been described.

Treatment (general principles)

Indications for treatment of chronic lymphocytic leukemia are deterioration of the general condition, the appearance of cytopenia, rapid enlargement of the lymph nodes, spleen, liver, the occurrence of leukemic infiltration of nerve trunks and non-hematopoietic organs, leading to pain syndrome or dysfunction; a steady increase in the level of leukocytes. In case of primary resistance to chlorbutin, it is not re-prescribed. The dose of chlorbutine for maintenance therapy is 10-15 mg 1-2 times a week.

Cyclophosphamide is prescribed for chronic lymphocytic leukemia, resistant to chlorbutin, as well as an increase in leukocytosis, significant enlargement of the lymph nodes or spleen and a tendency to thrombocytopenia. The dose of cyclophosphamide is 2 mg/kg per day. Intermittent treatment with large doses of 600 mg/m2 once a week may be effective. The effect of cyclophosphamide is unstable, the drug suppresses immunogenesis, so it should not be used for a long time.

Steroid hormones occupy a special place in the treatment of chronic lymphocytic leukemia: they lead to a rapid reduction of lymph nodes, removal of intoxication, normalization of temperature, improvement of well-being, but there is nothing more dangerous than prescribing prednisolone for the treatment of these patients.

Isolated therapy with prednisolone or its addition as a permanent drug to another intermittent cytostatic therapy or leukapheresis is deadly due to very frequent and severe infectious complications, on the one hand, and is very ineffective in oncological terms, on the other. The reduction of lymph nodes is accompanied by an increase in leukocytosis, normalization of temperature and the disappearance of other signs of intoxication are observed only with constant use of prednisolone, and resume with even greater force immediately after its discontinuation.

Due to the withdrawal syndrome, which is peculiar in lymphoproliferative mature cell tumors, even after using cytostatic programs, which include prednisolone (COP, VAMP), it is necessary to begin reducing its dose until the end of the program treatment and continue using it, reducing the dose, for several days after the end of the program.

For chronic lymphocytic leukemia, one of the effective treatments is radiation therapy. With the growth of peripheral lymph nodes abdominal cavity in conditions of cytopenia or with a high level of leukocytes and thrombocytopenia, significant size of the spleen, leukemic infiltration in the area of nerve trunks or a destructive process in bone tissue, local radiation therapy becomes necessary.

With local irradiation single dose is 1.5-2 Gy. The total dose to the lesion is determined by its location. The spleen, as a rule, is irradiated with a total dose of 6-9 Gy, since large doses can lead to deep cytopenia, which requires constant monitoring of peripheral blood during treatment. Irradiation of the spleen leads to a decrease in not only this organ, but often the cervical and axillary lymph nodes. When a vertebra is destroyed, the local total radiation dose is 25 Gy. Local radiation therapy often produces a lasting effect: in the irradiated area, as a rule, lymphatic infiltration does not worsen.

Fractionated total irradiation for chronic lymphocytic leukemia was successfully used in the 1950s by Osgood (1951, 1955). This method of radiation therapy can be effective where chemotherapy is difficult to use or has proven ineffective.

Removal of the spleen has become widely used in the complex of therapeutic measures for chronic lymphocytic leukemia. The development of deep cytopenias not caused by cytostatics requires the administration of glucocorticosteroid hormones. If a month's course of hormones does not produce a lasting effect and, following their withdrawal, cytopenia begins to increase again, then it is necessary to remove the spleen.

Another important indication for spleen removal is the size of the spleen. If in case of splenic lymphocytoma the diagnosis of the tumor itself is the basis for splenectomy, then in case of chronic lymphocytic leukemia with splenomegaly the question of surgery is not resolved so clearly. In chronic lymphocytic leukemia, after surgery, a fairly rapid enlargement of the liver may occur as a result of progressive lymphocytic proliferation in it.

Also, indications for removal of the spleen in chronic lymphocytic leukemia are rapid growth of the spleen, not controlled by cytostatics, the appearance of splenic infarctions, persistent pain in the left hypochondrium, very large organ sizes with uncontrollability of the process medications(increasing leukocytosis, exacerbation of infections, incipient exhaustion, concomitant enlargement of the liver, persistent non-infectious increase in temperature).

Leukopheresis is used in cases of severe leukocytosis, in which cytostatic therapy usual doses drugs turn out to be ineffective; Leukopheresis is usually effective for thrombocytopenia and agranulocytosis in the presence of high leukocytosis.

Plasmapheresis for chronic lymphocytic leukemia is used in cases of hyperviscosity syndrome that develops in secreting forms of the disease (Waldenström disease, chronic lymphocytic leukemia with monoclonal secretion of immunoglobulin G); long-term plasmapheresis is indicated for polyneuritis complicating lymphatic proliferation.

Treatment of individual forms

In the benign form of chronic lymphocytic leukemia, treatment with cytostatics does not begin for a long time. The indication for cytostatic therapy is an increase in subjective discomfort (weakness, sweating) with an increase in the number of leukocytes; as a rule, it already reaches 50 × 103 in 1 µl. In this case, therapy with chlorbutin (Leukeran) is started in daily dose 5-10 mg under blood control, trying not to exceed the threshold of 2 H 104 - 3 H 104 in 1 µl in reducing leukocytosis. Treatment does not aim to achieve improvement, but only clinical compensation; it is performed on an outpatient basis, and usually patients are able to work.

In the case of a progressive form, the most appropriate principle of treatment for many years was a primarily restraining approach, the essence of which boils down to limiting the leukemic process with constant moderate doses of cytostatic drugs already in its early stages, when leukocytosis has not yet reached very high numbers. The following programs are used.

Chlorobutin at a dose of 5-10 mg/day or cyclophosphamide at a dose of 200 mg/day (with a predominant increase in the number of leukocytes against the background of moderate lymphadenopathy, chlorbutin is usually preferred; for severe lymphadenopathy against the background of a slowly growing and not very high leukocytosis, cyclophosphamide is often prescribed). The goal of cytostatic therapy is to achieve somatic compensation with hematological stability against the background of low, preferably less than 50 H 103 in 1 μl, leukocytosis in the blood.

M-2 program (Kempin et al): on the 1st day of the course, 2 mg of vincristine, 600-800 mg of cyclophosphamide (10 mg/kg), BCNU at the rate of 0.5 mg/kg are administered intravenously; the remaining drugs are given orally - melphalan (alkeran) 0.25 mg/kg (or sarcolysin 0.3 mg/kg) once a day for 4 days in a row, prednisolone at a dose of 1 mg/(kg/day) for 7 days, half this dose for the next 7 days and a quarter of the original dose for 15-35 days of treatment. According to the authors, the treatment program they developed allows for remission in 17% of cases with an average patient life of more than 7 years. Discontinuation of treatment led to relapse.

Treatment of the tumor form of chronic lymphocytic leukemia also turned out to be more successful when using intensive polychemotherapy programs - COP, CHOP, M-2 (BCNU, cyclophosphamide, sarcolysine, vincristine, prednisolone). Remissions have been described when using the M-2 program (Kempin et al), which persist only with continued treatment. The first 2 programs relatively rarely lead to remission, but allow for a significant reduction in lymph nodes, which is especially important for conglomerates in the abdominal cavity. To maintain the achieved improvement, monotherapy can be used - intermittent courses of cyclophosphamide.

Multiple repetitions of courses of COP and CHOP are quite difficult for patients with chronic lymphocytic leukemia, since the abolition of prednisolone in these courses often leads to a sudden rise in temperature to 37.5 ° C, a sharp deterioration in general condition, sweating, weakness, and a significant increase in infections. When conducting these courses, it is necessary to begin reducing the dose of prednisolone on the 9-10th day of treatment, delaying its cancellation for 3-6 days after the end of the course.

After achieving stable improvement with courses of COP or CHOP (usually 6 courses), intermittent therapy with cyclophosphamide is prescribed after 2 weeks: 200 mg of cyclophosphamide orally daily or every other day for 5 or 10 days, respectively (total dose of the drug 1000 mg), a break between courses 10-12 days. When the level of platelets decreases - less than 1.5 H 103 in 1 μl, or leukocytes - less than 4-5 H 103 in 1 μl, the breaks between courses of cyclophosphamide are extended until these indicators improve or normalize.

The duration of intermittent therapy with cyclophosphamide is unpredictable: it is carried out to achieve a stable compensated state of patients.

As an independent program for the treatment of the tumor form of the disease, fractional total irradiation of 0.03-0.06-0.12 Gy per session daily is used, the total dose is 0.5-1.2 GY (Johnson, Rubin et al). This therapy can be dangerous if the leukocyte level is below 2,103 per 1 μl.

If polychemotherapy programs are ineffective, local radiation therapy is used in the area of enlarged lymph nodes and the spleen. Usually the spleen is irradiated first (if there is a sharp enlargement of the tonsils, they are the first to be irradiated); a further irradiation program is planned depending on the decrease in peripheral nodes and leukocytosis after irradiation of the spleen.

In the treatment of the splenomegalic form, removal of the spleen is often used as the first stage, which often leads to many years of somatic compensation for patients with hematological stability without additional treatment. The manifestation of subjective disorders (sweating, weakness, decreased ability to work), an increase in leukocytosis, and progressive enlargement of the liver after surgery require the appointment of cytostatic therapy in accordance with the clinical and hematological picture of the developing disease.

Treatment of the bone marrow form of chronic lymphocytic leukemia (lymphadenia ossium) carried out using the VAMP program: 8 days of treatment and 9 days of break. Treatment under this program is prescribed in full dose, despite the initially low numbers of leukocytes and platelets. At least 8-10 courses are carried out, although after 3-4 courses the blood and bone marrow picture usually already shows complete improvement.

Treatment programs for the cytolytic process in lymphocytic leukemia almost always begin with prescribing prednisolone at a dose of 60-80-100 mg/day until cytolysis is permanently stopped. If high cytolysis is not stopped within a month of prednisolone therapy, then steroid therapy should be abandoned and splenectomy should be performed.

The cytolytic process that develops with high leukocytosis can often be stopped with leukapheresis. Usually 5-7 leukopheresis are performed before positive effect. Leukopheresis turned out to be most effective in the thrombocytolytic process. The risk of removing simultaneously with leukocytes and a certain amount of platelets, the content of which in the blood is already low, is small: usually, after the first leukopheresis, bleeding decreases, although there is no increase in platelets yet.

After the cessation of the cytolytic process, therapy is carried out according to the form of chronic lymphocytic leukemia. In case of relapse of cytolysis against the background of moderate lymphadenopathy, it is advisable to use the VAMP regimen.

In some cases, chronic lymphocytic leukemia with cytolysis is accompanied by a pronounced increase in temperature, but this in itself does not become a basis for changing the usual treatment program. The nature of this temperature increase is unknown.

The partial disappearance of any sprout in the bone marrow suggests intramedullary cytolysis, probably caused by antibodies to bone marrow cells or the cytotoxic effect of the lymphocytes themselves. This syndrome is treated in the same way as overt peripheral cytolysis.

Therapy commonly used for chronic lymphocytic leukemia is generally ineffective in the prolymphocytic form. In contrast to the splenomegalic form of chronic lymphocytic leukemia, irradiation and removal of the spleen have no effect. A combination of cytosar with rubomycin may be more effective.

Chronic lymphocytic leukemia with paraprotein production is treated according to the same principles as the other forms of the disease described above, but not associated with the secretion of immunoglobulin. Since the secreting form of the disease can occur both as benign and as progressive, tumor, bone marrow, splenomegalic, it is treated according to the same cytostatic programs as the corresponding forms. An important addition to cytostatic therapy is plasmapheresis, prescribed for hyperviscosity syndrome.

The most effective treatment for the hairy cell form is splenectomy. Long-term therapy with chlorbutin in small doses is effective - 2-4 mg per day. Normalization of blood composition with this therapy occurs 6-10 months from the start of treatment. Deoxycoformycin (an inhibitor of adenosine deaminase, highly active in T cells), a combination of small doses of vinblastine and chlorobutine, and interferon are also used.

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Chronic lymphocytic leukemia - benign tumor, consisting of mature atypical lymphocytes that accumulate not only in the blood, but also in the bone marrow and lymph nodes.

The disease, which belongs to the group of non-Hodgkin's lymphomas, accounts for about a third of all leukemias. According to statistics, chronic lymphocytic leukemia is more common in men 50-70 years old; young people suffer from it extremely rarely.

Causes of chronic lymphocytic leukemia

At the moment, the true causes of the development of the disease are unknown. Scientists could not even prove the dependence of lymphocytic leukemia on aggressive environmental factors. The only confirmed point is hereditary predisposition.

Classification of chronic lymphocytic leukemia

Depending on the signs of the disease, examination data and the response of the human body to the therapy, the following variants of chronic lymphocytic leukemia are distinguished.

Chronic lymphocytic leukemia with a benign course

The most favorable form of the disease, progression is very slow and can last several years. The leukocyte level increases slowly, the lymph nodes remain normal, and the patient maintains his usual lifestyle, work and activity.

Progressive chronic lymphocytic leukemia

A rapid increase in the level of leukocytes in the blood and enlargement of the lymph nodes. The prognosis of the disease in this form is unfavorable; complications and death can develop quite quickly.

Tumor form

A significant increase in lymph nodes is accompanied by a slight increase in the level of leukocytes in the blood. Lymph nodes, as a rule, do not cause pain when touched and only when they reach a large size can they cause aesthetic discomfort.

Bone marrow form

The liver, spleen and lymph nodes remain unaffected, only changes in the blood are observed.

Chronic lymphocytic leukemia with enlarged spleen

This type of leukemia, as the name suggests, is characterized by an enlarged spleen.

Prelymphocytic form chronic lymphocytic leukemia

A distinctive feature of this form is the presence of lymphocytes containing nucleoli in blood and bone marrow smears, tissue samples of the spleen and lymph nodes.

Hairy cell leukemia

This form of the disease got its name due to the fact that under a microscope it is found tumor cells with "hairs" or "villi". There is cytopenia, that is, a decrease in the level of basic cells or shaped elements blood, and enlarged spleen. The lymph nodes remain unaffected.

T-cell form of chronic lymphocytic leukemia

One of the rare forms of the disease, prone to rapid progression.

Symptoms of chronic lymphocytic leukemia

The disease occurs in three successive stages: initial, advanced stage clinical manifestations and terminal.

Symptoms of the initial stage

At this stage, the disease in most cases is hidden, that is, asymptomatic. Leukocyte count in general analysis blood is close to normal, and the level of lymphocytes does not exceed the 50% mark.

The first real sign of the disease is persistent enlargement of the lymph nodes, liver and spleen.

The axillary and cervical lymph nodes, nodes in the abdominal cavity and groin area are gradually involved.

Large lymph nodes, as a rule, are painless on palpation and do not cause significant discomfort, except for aesthetic (with large sizes). The enlarged liver and spleen can put pressure on internal organs, impairing digestion, urination, and causing a number of other problems.

Symptoms of the stage of advanced clinical manifestations

At this stage of chronic lymphocytic leukemia, increased fatigue and weakness, apathy and decreased ability to work may be observed. Patients complain of profuse night sweats, chills, slight increase body temperature and causeless weight loss.

The level of lymphocytes is steadily increasing and has already reached 80-90%, while the number of other blood cells remains unchanged, in some cases platelets decrease.

End stage symptoms

As a result of a progressive decrease in immunity, patients often suffer from colds, suffer from infections of the genitourinary system and pustules on the skin.

Severe pneumonia accompanied by respiratory failure, generalized herpes infection, renal failure - that’s far from full list complications caused by chronic lymphocytic leukemia.

As a rule, it is severe, multiple diseases that cause death in chronic lymphocytic leukemia. Other causes of death include exhaustion, severe renal failure and bleeding.

Complications of chronic lymphocytic leukemia

In the terminal stage of the disease, infiltration of the auditory nerve is observed, leading to hearing impairment and constant noise in the ears, as well as damage to the meninges and nerves.

In some cases, chronic lymphocytic leukemia develops into another form - Richter syndrome. The disease is characterized by rapid progression and the formation of pathological foci outside the lymphatic system.

Diagnosis of chronic lymphocytic leukemia

In 50% of cases, the disease is discovered by chance during a blood test. After which the patient is referred for a consultation with a hematologist and a specialized examination.

As the disease progresses, a blood smear analysis becomes informative, in which the so-called “crushed leukocytes”, or Botkin-Gumprecht shadows (Botkin-Gumprecht bodies), are visualized.

A biopsy of lymph nodes is also performed, followed by cytology of the obtained material, and immunotyping of lymphocytes. Detection of pathological antigens CD5, CD19 and CD23 is considered a reliable sign of the disease.

The degree of enlargement of the liver and spleen on ultrasound helps the doctor determine the stage of development of chronic lymphocytic leukemia.

Treatment of chronic lymphocytic leukemia

Chronic lymphocytic leukemia - systemic disease, and therefore radiation therapy is not used in its treatment. Drug therapy includes the use of several groups of drugs.

Hormones corticosteroids

Corticosteroids inhibit the development of lymphocytes, so they can be used in complex therapy of chronic lymphocytic leukemia. But at present they are rarely used, due to a large number of serious complications that call into question the advisability of their use.

Alkylating drugs

Among alkylating agents, Cyclophosphamide is the most popular in the treatment of chronic lymphocytic leukemia. It has shown good effectiveness, but can also cause serious complications. The use of the drug often leads to a sharp decrease in the level of red blood cells and platelets, which is fraught with severe anemia and bleeding.

Vinca alkaloid preparations

The main drug in this group is Vincristine, which blocks cell division. cancer cells. The drug has a number of side effects, such as neuralgia, headaches, increased blood pressure, hallucinations, sleep disturbances and loss of sensitivity. In severe cases, muscle cramps or paralysis occur.

Anthracyclines

Anthracyclines are drugs with a dual mechanism of action. On the one hand, they destroy the DNA of cancer cells, causing their death. On the other hand, they form free radicals, which do the same thing. This active influence, as a rule, helps to achieve good results.

However, the use of drugs in this group often causes complications from the cardiovascular system in the form of rhythm disturbances, failure, and even myocardial infarction.

Purine analogues

Purine analogues are antimetabolites, which, being built into metabolic processes, disrupt their normal course.

In the case of cancer, they block the formation of DNA in tumor cells, therefore inhibiting the processes of growth and reproduction.

The most important advantage of this group of drugs is their relatively easy tolerability. Treatment usually gives good effect, and the patient does not suffer from serious side effects.

Monoclonal antibodies

Drugs belonging to the group of “monoclonal antibodies” are currently considered the most effective means for the treatment of chronic lymphocytic leukemia.

The mechanism of their action is that when antigen and antibody bind, the cell receives a signal to die and dies.

The only danger is side effects, the most severe of which is decreased immunity. This creates high risk the occurrence of infections, up to generalized forms in the form of sepsis. Such treatment should be carried out only in specialized clinics where sterile rooms are equipped and the risk of infection is minimal. It is recommended that the patient remain in such conditions not only directly during therapy, but also for two months after its completion.

For many people, the diagnosis of lymphocytic leukemia or blood cancer sounds like a death sentence. But few people know that over the past 15 years a powerful medicinal arsenal, thanks to which it is possible to achieve long-term remission or the so-called “relative cure”, and even the abolition of pharmacological drugs.

Leading clinics abroad

What is lymphocytic leukemia and what are the causes of its occurrence?

This cancer, in which leukocytes, bone marrow, peripheral blood are affected, and lymphoid organs are involved in the process.

Scientists are inclined to believe that the cause of the disease is at the genetic level. The so-called family predisposition is very pronounced. It is believed that the risk of developing the disease in close relatives, namely children, is 8 times higher. However, no specific gene causing the disease was found.

The disease is most common in America, Canada, and Western Europe. And lymphocytic leukemia is almost rare in Asian countries and Japan. Even among Asians who were born and raised in America, this disease is extremely rare. Such long-term observations led to the conclusion that environmental factors do not affect the development of the disease.

Lymphocytic leukemia can also develop as a secondary disease after radiation therapy (in 10% of cases).

It is believed that some congenital pathologies may lead to the development of the disease: Down syndrome, Wiskott-Aldrich syndrome.

Forms of the disease

Acute lymphocytic leukemia (ALL) is a cancer that is morphologically represented by immature lymphocytes (lymphoblasts). There are no specific symptoms that can be used to make a definite diagnosis.

Chronic lymphocytic leukemia (CLL) is a tumor consisting of mature lymphocytes and is a long-term, indolent disease.

Symptoms

Symptoms characteristic of LL:

enlargement of peripheral lymph nodes, liver, spleen;
increased sweating, skin rashes, slight increase in temperature:
loss of appetite, weight loss, chronic loss of strength;
muscle weakness, bone pain;
immunodeficiency ─ the immunological reactivity of the body is disrupted, infections occur;
immune hemolysis ─ damage to red blood cells;
immune thrombocytopenia ─ leads to hemorrhages, bleeding, the presence of;
secondary tumors.

Leading specialists from clinics abroad

Stages of lymphocytic leukemia depending on the form of the disease

Stages of ALL:

Primary attack ─ the period when the first symptoms appear, see a doctor, and make an accurate diagnosis.
Remission (weakening or disappearance of symptoms) ─ occurs after treatment. If this period lasts more than five years, then the patient is diagnosed with complete recovery. However, a clinical blood test must be performed every six months.
Relapse ─ resumption of the disease against the background of apparent recovery.
Resistance ─ immunity and resistance to chemotherapy, when several courses of treatment have failed.
Early mortality ─ the patient dies during chemotherapy treatment.

The stages of CLL depend on blood counts and the degree of involvement of lymphoid organs (lymph nodes of the head and neck, armpits, groin, spleen, liver) in the pathological process:

Stage A ─ pathology covers less than three areas, severe lymphocytosis, low risk, survival more than 10 years.
Stage B ─ three or more areas are affected, lymphocytosis, average or intermediate risk, survival 5-9 years.
Stage C ─ all lymph nodes are affected, lymphocytosis, thrombocytopenia, high risk, survival 1.5-3 years.

What is included in the diagnosis?

Standard examinations for diagnosis:

Clinical research methods ─ detailed blood test (leukocyte formula).
Immunophenotyping of leukocytes is a diagnostic that characterizes cells (determines their type and functional state). This allows us to understand the nature of the disease and predict its further development.
Bone marrow trepanobiopsy is a puncture with extraction of a complete fragment of bone marrow. For the method to be as informative as possible, the tissue taken must retain its structure.
Cytogenetic research is mandatory in oncohematology. The method involves analyzing the chromosomes of bone marrow cells under a microscope.
Molecular biological research ─ gene diagnostics, DNA and RNA analysis. Helps diagnose the disease in the early stages, plan and justify further treatment.
Immunochemical study of blood and urine ─ determines the parameters of leukocytes.

Modern treatment of lymphocytic leukemia

The approach to treating ALL and CLL is different.

Therapy for acute lymphocytic leukemia takes place in two stages:

The first stage is aimed at achieving stable remission by destroying pathological leukocytes in the bone marrow and blood.
The second stage (post-remission therapy) is the destruction of inactive leukocytes, which in the future can lead to relapse.

Standard treatments for ALL:

Chemotherapy

Systematic (drugs enter the general bloodstream), intrathecal (chemical drugs are injected into the spinal canal where the cerebrospinal fluid), regional (medicines act on a specific organ).

Radiation therapy

It can be external (irradiation with a special apparatus) and internal (placing hermetically sealed radioactive substances in the tumor itself or near it). If there is a risk of tumor spreading to the central nervous system, external beam radiation therapy is used.

TCM or THC

Bone marrow or hematopoietic stem cell (blood cell precursor) transplantation.

Biological therapy

Aimed at restoring and stimulating the patient's immunity.

Restoration and normalization of bone marrow function occurs no earlier than two years after chemotherapy treatment.

CLL is treated with chemotherapy and TKI therapy, tyrosine kinase inhibitors. Scientists have isolated proteins (tyrosine kinases) that promote the growth and production of white blood cells from stem cells. TKI drugs block this function.

Prognosis and life expectancy

Cancer diseases rank second in the world in terms of mortality. The share of lymphocytic leukemia in these statistics does not exceed 2.8%.

Important!

The acute form mainly develops in children and adolescents. The prognosis for a favorable outcome in the conditions of innovative treatment technologies is very high and amounts to more than 90%. At the age of 2-6 years, almost 100% recovery occurs. But one condition must be met - timely seeking specialized medical help!

Chronic form─ this is a disease of adults. There is a clear pattern in the development of the disease associated with the age of the patients. The older the person, the Great chance occurrence . For example, at 50 years old there are 4 cases per 100,000 people, and at 80 years old this is already 30 cases per the same number of people. The peak of the disease occurs at 60 years of age. Lymphocytic leukemia It is more common in men, accounting for 2/3 of all cases. The reason for this sexual differentiation is not clear. The chronic form is incurable, but the prognosis for ten-year survival is 70% (over these years the disease never relapses).