Chronic myeloid leukemia. Chronic myeloid leukemia - life expectancy at different stages of the course of the disease

• Prevention of chronic myeloid leukemia
• Which Doctors Should You See If You Have Chronic Myeloid Leukemia?

What is Chronic Myeloid Leukemia

Chronic myeloid leukemia (CML) ranks third among all leukemias. It accounts for about 20% of blood cancer cases. At the moment, more than 3 thousand patients are registered in Russia. The youngest of them is only 3 years old, the oldest is 90.

Incidence of CML is 1-1.5 cases per 100,000 population per year (15-20% of all cases of hemoblastoses in adults). Mostly middle-aged people are ill: the peak incidence occurs at the age of 30-50 years, about 30% are patients over 60 years of age. In children, CML is rare, accounting for no more than 2-5% of all leukemias. Men get sick more often than women (ratio 1:1.5).

What causes chronic myeloid leukemia

Like the vast majority of other leukemias, chronic myeloid leukemia occurs as a result of acquired (i.e., not congenital) damage to the chromosomal apparatus of a single bone marrow stem cell.

The exact cause of this chromosome change in CML patients is still unknown. Most likely, there is a random exchange of genetic material between chromosomes, which at a certain stage of cell life are located in close proximity to each other.

Remains controversial issue about the impact on the incidence of CML of factors such as low doses of radiation, weak electromagnetic radiation, herbicides, insecticides, etc. An increase in the incidence of CML in people exposed to ionizing radiation has been reliably proven. Among chemical agents, only benzene and mustard gas have been associated with the occurrence of CML.

Substrate of chronic myelogenous leukemia make up mainly maturing and mature cells of the granulocytic series (metamyelocytes, stab and segmented granulocytes).

Pathogenesis (what happens?) during Chronic myeloid leukemia

It is believed that the t(9;22) translocation, which leads to the formation of the chimeric BCR-ABL1 gene, plays a key role in the development of chronic myelogenous leukemia. In this case, the 1st exon of the ABL1 gene is replaced by a different number of 5'-terminal exons of the BCR gene. Bcr-Abl chimeric proteins (one of them is the p210BCR-ABL1 protein) contain N-terminal Bcr domains and C-terminal Abl1 domains.

The ability of chimeric proteins to induce tumor transformation of normal hematopoietic stem cells has been demonstrated in vitro.

The oncogenicity of the p210BCR-ABL1 protein is also evidenced by experiments on mice that received a lethal dose of radiation. When they were transplanted with bone marrow cells that were infected with a retrovirus carrying the BCR-ABL1 gene, half of the mice developed a myeloproliferative syndrome that resembled chronic myelogenous leukemia.

Other evidence for the role of the p210BCR-ABL1 protein in the development of chronic myeloid leukemia comes from experiments with antisense oligonucleotides complementary to the BCR-ABL1 gene transcript. These oligonucleotides have been shown to inhibit the growth of tumor cell colonies, while normal granulocytic and macrophage colonies continue to grow.

The fusion of the BCR gene with the ABL1 gene leads to an increase in the tyrosine kinase activity of the Abl1 protein, a weakening of its ability to bind to DNA, and an increase in binding to actin.

At the same time, the detailed mechanism of transformation of normal bone marrow cells into tumor cells is unknown.

The mechanism of transition of the disease from the advanced stage to the blast crisis is also unclear. The tumor clone is characterized by chromosome fragility: in addition to the t (9; 22) translocation, trisomy on the 8th chromosome and a deletion in 17p may appear in tumor cells. The accumulation of mutations leads to a change in the properties of tumor cells. According to some researchers, the rate of development of a blast crisis depends on the localization of the BCR gene break point. Other researchers refute these data.

In a number of patients, the development of a blast crisis is accompanied by various mutations in the TP53 gene and the RB1 gene. Mutations in the RAS genes are rare. There are isolated reports of the appearance of the p190BCR-ABL1 protein in patients with chronic myeloid leukemia (it is often found in patients with acute lymphoblastic leukemia and sometimes in patients with acute myeloid leukemia), as well as mutations in the MYC gene.

Prior to a blast crisis, DNA methylation may occur at the BCR-ABL1 gene locus.

There is also information about the participation of IL-1beta in the progression of chronic myeloid leukemia.

The presented data indicate that tumor progression is due to several mechanisms, but the exact role of each of them is unknown.

Symptoms of Chronic Myeloid Leukemia

The moment of occurrence chronic myeloid leukemia, like any other leukemia, has no symptoms and always goes unnoticed. Symptoms develop when the total number of tumor cells begins to exceed 1 kilogram. Most patients complain of general malaise. They get tired faster and physical work they may become short of breath. As a result of anemia, the skin becomes pale. Patients may experience discomfort in the left side abdominal cavity caused by an enlarged spleen. Often, patients lose weight, note increased sweating, weight loss, and an inability to tolerate heat. At clinical examination most often the only pathological sign is an enlarged spleen. An increase in the size of the liver and lymph nodes in the early stage of CML is practically not found. Approximately a quarter of patients with chronic myeloid leukemia are discovered quite by accident, during a routine medical examination. Sometimes the diagnosis of CML is made already at a more aggressive stage - acceleration or blast crisis.

Chronic myeloid leukemia (chronic myelosis) occurs in two stages.

The first stage is benign, lasts several years, and is characterized by an enlarged spleen.

The second stage - malignant, lasts 3-6 months. spleen, liver, The lymph nodes enlarged, leukemic infiltrations of the skin, nerve trunks appear, meninges. Hemorrhagic syndrome develops.

Infectious diseases are often recorded. Typical signs of intoxication are weakness, sweating. Sometimes the first symptom is a slight pain, heaviness in the left hypochondrium, which is associated with an enlarged spleen, followed by spleen infarcts. Without apparent reason the temperature rises, bone pains appear.

In a typical case, neutrophilic leukocytosis (an increase in the level of neutrophilic leukocytes) is characteristic with the appearance of young forms of neutrophils, accompanied by an increase in the number of platelets, a decrease in the content of lymphocytes. As the disease progresses, anemia and thrombocytopenia increase. In children, the juvenile form of chronic myeloid leukemia is more often observed without an increase in the number of platelets, but with an increased content of monocytes. The number of basophils often increases, and there is an increased level of eosinophils. First benign stage bone marrow cells are normal in all respects. In the second stage, blast forms appear in the bone marrow and blood, it is noted fast growth the number of leukocytes in the blood (up to several million in 1 μl). Characteristic features the final stage is the detection in the blood of fragments of the nuclei of megakaryocytes, the inhibition of normal hematopoiesis.

The disease is chronic with periods of exacerbation and remissions. The average life expectancy is 3-5 years, but there are isolated cases of a long course of chronic myeloid leukemia (up to 10-20 years). The clinical picture depends on the stage of the disease.

Forecast is ambiguous and depends on the stage of the disease. During the first two years after the diagnosis, 10% of patients die, each subsequent year - a little less than 20%. The median survival is approximately 4 years.

To determine the stage of the disease and risk lethal outcome using predictive models. Most often, these are models based on a multivariate analysis of the most important prognostic features. One of them - the Sokal index - takes into account the percentage of blast cells in the blood, the size of the spleen, the number of platelets, additional cytogenetic disorders and age. The Tour model and the combined Kantarjan model take into account the number of unfavorable prognostic signs. These features include: age 60 and older; significant splenomegaly (the lower pole of the spleen protrudes from the left hypochondrium by 10 cm or more); the content of blast cells in the blood or in the bone marrow, equal to or greater than 3% and 5%, respectively; the content of basophils in the blood or in the bone marrow, equal to or greater than 7% and 3%, respectively; platelet count equal to or greater than 700,000 1/µl, as well as all signs of the acceleration stage. In the presence of these signs, the prognosis is extremely unfavorable; the risk of death during the first year of the disease is three times higher than usual.

Diagnosis of chronic myeloid leukemia

Picture of blood and bone marrow In a typical case, neutrophilic leukocytosis is characteristic with the appearance of young forms of neutrophils, accompanied by hyperthrombocytosis, lymphocytopenia. As the disease progresses, anemia and thrombocytopenia increase. Children often have a juvenile form of chronic myeloid leukemia without hyperthrombocytosis, but with high monocytosis. The number of basophils often increases, eosinophilia occurs. In the first benign stage, bone marrow cells correspond to the norm in all respects. In the second stage, blast forms appear in the bone marrow and blood, there is a rapid increase in the number of leukocytes in the blood (up to several million in 1 μl). The characteristic signs of the terminal stage are the detection in the blood of fragments of the nuclei of megakaryocytes, the inhibition of normal hematopoiesis.

The diagnosis of chronic leukemia is established on the basis of complaints, examination, blood tests, biopsy, cytogenetic analysis. Help in establishing the diagnosis and such auxiliary examination methods as PET-CT, CT, MRI.

The diagnosis is based on the blood picture. Of decisive importance is the puncture of the bone marrow. Differential diagnosis is carried out with lymphogranulomatosis and lymphosarcomatosis.

Treatment of chronic myeloid leukemia

In the advanced stage of the disease, small doses of myelosan are prescribed, usually for 20-40 days. With a drop in leukocytes to 15,000-20,000 per 1 μl (15-20 G / l), they switch to maintenance doses. In parallel with myelosan, irradiation of the spleen is used. In addition to myelosan, it is possible to prescribe myelobromine, 6-mercaptopurine, hexaphosphamide, hydroxyurea. At the stage of a blast crisis, a combination of drugs gives a good result: vincristine-prednisolone, cytosar-rubomycin, cytosarthioguanine. Apply bone marrow transplantation.

Chronic myeloid leukemia (CML) is a neoplastic clonal disease of a multipotent hematopoietic stem cell predominantly involving the granulocytic cell line.

The disease was first described by R. Virchow in the middle of the 19th century under the name "splenic leukemia". CML accounts for approximately 20% of all leukemias in Europe.

It is more common in middle-aged and older adults with a median age of about 50 years, although CML can develop at any age.

There is no dependence in incidence on gender and ethnicity.

The etiology of CML is unknown. Among atomic bomb survivors in Japan, an increase in the incidence of CML was observed after a three-year period. latent period peaking at 7 years. In a group of patients in the UK who received radiation therapy about ankylosing spondylitis, there was an increase in the incidence of chronic myeloid leukemia after a latent period of 13 years.

Overall impact ionizing radiation noted in history less than 5% of patients with CML. Contact with myelotoxic agents was detected in isolated cases. Although an increase in the frequency of expression of the HLA-Cw3 ​​and HLA-Cw4 antigens has been noted in CML, there are no reports of cases of familial CML. The incidence of CML is 1.5 per 100,000 population.

In 1960, G. Nowell and D. Hungerford found in patients with CML a shortening of the long arm of one chromosome (Xp), as they believed, the 21st pair. They called this chromosome the Philadelphia or Ph chromosome.

However, in 1970 T.Caspersson et al. found that in chronic myeloid leukemia there is a deletion of one of the Xp 22 pairs. In 1973, J. Rowley showed that the formation of the Ph chromosome is due to reciprocal translocation (mutual transfer of part of the genetic material) between Xp9 and Xp22. This altered chromosome is from the 22nd pair with a shortened long arm and is designated as the Ph chromosome.

In the initial period of the cytogenetic study of CML, two variants, Ph+ and Ph-, were described. However, it must now be recognized that Ph-CML does not exist, and the reported cases probably belonged to myelodysplastic conditions. Ph-chromosome, t (9; 22) (q34; q11) is found in 95-100% of patients with CML.

In other cases, the following translocation options are possible:

Complex translocations involving Xp9, 22 and some third chromosome
- masked translocations with the same molecular changes, but not detected by conventional cytogenetic methods,
- the presence of t (9; 22) without transferring the Xp22 site to Xp9.

Thus, in all cases of CML, there are changes in Xp9 and Xp22 with the same gene rearrangement in a certain region of Xp22 (2).

The proto-oncogene ABL (Abelson) is located on the long arm of Xp9 (q34), which encodes, through the synthesis of specific mRNA, the formation of the p145 protein belonging to the family tyrosine kinase (TK)- enzymes that catalyze the processes of phosphorylation of amino acids in the cell cycle. The M-BCR region (Major breakpoint cluster region) is located on the long arm of Xp22 (q 11).

The gene located in this region is referred to as the BCR gene. It encodes the formation of the p160BCR protein, which is involved in the regulation of several functions of neutrophils. As a result of translocation t(9;22)(q34;q11), the c-acr proto-oncogene is transferred to the bcr Xp22 region.

Typically, the breakage of the BCR gene occurs between exons b2 and b3 or exons b3 and b4, and exon 2 of the ABL gene fuses with the remaining part of the BCR gene on Xp22 (with exon b2 or b3). As a result, a chimeric BCR-ABL gene is formed, encoding an abnormal 8.5 kb ribonucleic acid (mRNA), which produces the p210BCR-ABL fusion protein with tyrosine kinase activity.

Sometimes the breakpoint of the BCR gene is located in the m-BCR (minor breakpoint cluster region), while the production of the chimeric gene is 7.5 kb of mRNA encoding the p190BCR-ABL protein. This type of translocation is associated with the involvement of lymphoid cells in the process and often causes the development of Ph+ acute lymphoblastic leukemia (ALL).

Due to the activation of the ABL gene resulting from its fusion with the BCR gene, the p210BCR-ABL protein has a significantly more pronounced tyrosine kinase activity than its normal prototype p145ABL. MCs phosphorylate tyrosine in proteins that regulate the growth and differentiation of cells, including hematopoietic ones.

Mutations of tyrosine kinases with an increase in their activity lead to unregulated phosphorylation of tyrosine and, accordingly, to disruption of the processes of cell growth and differentiation. However, this is not the only and not the main mechanism in the pathogenesis of CML symptoms.

The biological effect of the chimeric BCR-ABL gene is reduced to the following main disturbances in the life of the cell:

An increase in mitogenic activity due to increased proliferation signal transmission by activating hematopoietic cell receptors due to increased phosphorylation. This not only enhances proliferation, regardless of the regulatory influence of growth factors, but also disrupts the differentiation of progenitor cells;

Violation of cell adhesion to the stroma, which leads to a decrease in the interaction time of the stroma/hematopoietic cells. The consequence of this is that the normal proliferation/maturation sequence is disrupted, so progenitor cells stay longer in the late progenitor proliferative phase before differentiation. This leads to an increase in the proliferation and circulation time of progenitor cells and the appearance of foci of extramedullary hematopoiesis;

Inhibition of apoptosis due to the protective effect of the p210 protein and activation of the MYC gene, which is an inhibitor of apoptosis, as well as due to overexpression of the BCL-2 gene. As a result, leukocytes in CML live longer than normal cells. A characteristic feature of the p210BCR-ABL protein is the ability to autophosphorylate, leading to autonomous cell activity and its almost complete independence from external regulatory mechanisms;

The emergence of an unstable cell genome due to a decrease in the function of the ABL gene, since its role as a tumor growth suppressor decreases with its deletion. As a result, cell proliferation does not stop. In addition, other cellular oncogenes are activated during proliferation, which leads to a further increase in cell proliferation.

Thus, an increase in proliferative activity, a decrease in sensitivity to apoptosis, a violation of differentiation processes, an increased ability of immature hematopoietic progenitor cells to exit the bone marrow into peripheral blood are the main characteristics of leukemic cells in chronic myeloid leukemia.

Chronic myeloid leukemia: phases of development, criteria for risk groups

The chronic phase (CP) of the disease in most cases is almost or completely asymptomatic. Complaints of fatigue, weakness, sometimes heaviness in the epigastrium. Examination can reveal an enlarged spleen and, very rarely, the liver.

The clinical and hematological picture may be asymptomatic, the number of leukocytes and platelets may be normal or slightly increased; in the leukocyte formula, a moderate left shift can be observed - single metamyelocytes and myelocytes, sometimes slight increase the number of basophils. At cytological examination only the Ph-chromosome is detected without additional changes from other chromosomes.

In the acceleration phase, patients note increased fatigue when performing their usual work, discomfort in the left hypochondrium; weight loss, periodic “unmotivated” increases in body temperature reflect the presence of hypercatabolism. As a rule, an enlarged spleen is determined, and in 20-40% of cases, an enlarged liver.

The main sign of the transition of the disease to FA are changes in blood tests: leukocytosis uncontrolled by cytostatic drugs increases with a quantitative predominance immature forms leukocytes, the number of basophils increases, less often the number of eosinophils or monocytes increases.

The number of platelets may increase with the development of thrombotic complications at the beginning of FA, followed by the development of thrombocytopenia with manifestations of hemorrhagic syndrome in the petechial-spotted type. In the bone marrow, FA shows a slight increase in the number of blast cells (usually less than 20%) and an increase in the content of promyelocytes and myelocytes. A cytogenetic study of FA, in addition to the presence of the Ph chromosome, can reveal additional changes in other chromosomes, which indicates the emergence of a more malignant cell clone.

In the phase of the blast crisis, there is a sharp general weakness, pronounced ossalgia due to subperiosteal infiltration by blast cells, periodic fever, sweating, and a pronounced decrease in body weight. Growing hepatosplenomegaly. As a rule, there is a pronounced hemorrhagic diathesis. Hematological manifestations are characterized by an increase in the number of blast cells in the peripheral blood and / or bone marrow above 20% with a variable number of leukocytes.

The predominant variant of CD is the myeloid variant - approximately 50% of all cases; lymphoblastic and undifferentiated variants - about 25% of cases each. Lymphoblastic CD has an extremely malignant nature, which is associated with changes in blast clones and, therefore, with resistance to ongoing therapy.

Sometimes CD is characterized by a sharp increase in the number of basophils of varying degrees of maturity in the peripheral blood and bone marrow without a large number blast cells. In some cases, basophilia is replaced by monocytosis.

Usually, there is normochromic anemia and thrombocytopenia of varying severity, normoblastosis, and fragments of megakaryocytes in a blood smear. Approximately 10-15% of patients in the CD phase develop extramedullary blast infiltrates.

Rarely, lesions of the central nervous system with symptoms of neuroleukemia or peripheral nerve damage. Some patients with CD have cutaneous leukemids or priapism as a result of leukostasis and leukemic infiltration of the cavernous bodies. It should be noted that in some cases, in the presence of extramedullary foci of blast infiltration, the picture of peripheral blood and bone marrow may not show signs of CML transition to the CD phase.

According to the WHO classification (2002), the following criteria have been identified for FA and CD.

The acceleration phase in the presence of one or more signs:

Blasts 10-19% in peripheral blood or bone marrow,
- basophils less than 20% in peripheral blood,
- persistent thrombocytopenia (less than 100.0x10 9 /l) or persistent thrombocytosis more than 1000.0x10 9 /l, despite ongoing therapy,
- an increase in the size of the spleen and an increase in the level of leukocytes, despite ongoing therapy,
- cytogenetic evidence in favor of clonal evolution (in addition to cytogenetic abnormalities identified at the time of diagnosis of HF CML),
- megakaryocytic proliferation in the form of clusters in combination with significant reticulin and collagen fibrosis and / or severe granulocytic dysplasia.

Power crisis phase in the presence of one or more of the following:

Blasts 20% or more in peripheral blood or bone marrow,
- extramedullary proliferation of blasts,
- large accumulations or clusters of blasts in the bone marrow during trephine biopsy.

The chronic phase of CML is established in the absence of FA criteria and the CD phase.

Splenomegaly and hepatomegaly of any size are not signs of FA and CCMLD.

It is important to determine not only the phase of CML, but also the risk group for disease progression at the onset of the disease, taking into account the data primary examination patient. J.E.Sokal et al. in 1987, they proposed a prognostic model taking into account four features: the age of the patient at the time of diagnosis, the size of the spleen, the number of platelets and the number of blasts in the blood. This model is the most widely used and is used in most studies.

The calculation of the prognostic index is carried out according to the formula:

Sokal index = exp(0.0116(age - 43.4) + 0.0345(spleen size - 7.51) + 0.188[(platelet count: 700)2 - 0.563] + 0.0887(blood blast count - 2.10)).

Exp (exponent) -2.718 is raised to the power of the number that appears in curly brackets.

If the index is less than 0.8 - low-risk group; with an index of 0.8-1.2 - a group of medium risk; with an index of more than 1.2 - a high-risk group.

Methods for diagnosing chronic myeloid leukemia

To mandatory methods examinations of patients to establish the diagnosis of CML include:

Morphological examination of peripheral blood with the calculation of the leukocyte formula and the number of platelets,
- morphological study bone marrow punctate,

Since the only reliable criterion for the diagnosis of chronic myeloid leukemia is the presence of the Ph chromosome, a cytogenetic study of the bone marrow with an analysis of at least 20 metaphase plates is necessary; with a negative answer - the absence of t (9; 22) (q34; q11) - with a high possibility of diagnosing CML, it is necessary to use molecular genetic techniques - FISH (fluorescence in situ hybridization) or polymerase chain reaction (PCR),
- palpation and ultrasound-determination of the size of the spleen, liver, lymph nodes. Since splenomegaly or hepatomegaly of any size are not criteria for FA or a phase of CD, a specific lesion of any other organs and tissues should be considered as a sign of the transformation of the disease into CD,

HLA typing for potential candidates on the allogeneic hematopoietic stem cell transplantation (allo-HSCT) indicated for patients with CML in FA and CD who have no contraindications to the use of this treatment method,
- patients in the CD phase of CML are shown to determine the type of blasts by cytochemical examination and immunophenotyping.

Optional examination methods include:

Trepanobiopsy to assess the presence and extent of fibrosis in the bone marrow,
- instrumental methods examinations - ultrasound procedure(ultrasound), magnetic resonance imaging (MRI), lumbar puncture in order to determine the presence of extramedullary foci of hematopoiesis,
- before starting therapy tyrosine kinase inhibitors (TKIs) it is advisable to perform PCR to determine the initial level of expression of the BCR-ABL gene.

Therapy for chronic myelogenous leukemia

Standard allo-HSCT caused long-term molecular remission or recovery in 50% of patients with a significant difference when taking into account risk groups. In countries where TKI therapy is available and allo-HSCT is performed, the two strategies are not mutually exclusive, although since the introduction of TKI into clinical practice, there has been a noticeable decrease in the annual number of allo-HSCT in the last 7 years.

The effectiveness of the therapy is determined by the following criteria:

1. The presence of hematological remission: data from blood tests:

- complete clinical and hematological remission (CHR):
- platelets below 450.0x10%,
- white blood cells below 10.0x10%,
- in the leukogram, blasts are less than 5%, there are no immature granulocytes.

2. The presence of cytogenetic remission: the presence of Ph chromosomes:

Full - 0%,
- partial - 1-35%,
- small - 36-65%,
- minimum - 66-95%.

3. Presence of molecular remission: presence of BCR-ABL transcript:

Complete - the transcript is not determined,
- large - 0.1%.

Complete cytogenetic (CCyR) and partial cytogenetic remission (PCyR) in combination can be considered as major cytogenetic remission (MCyR). Major molecular remission (MMolR) is the equivalent of a 1000-fold reduction from basic level at 100%.

Complete molecular remission (CMolR) it is stated if the BCR-ABL transcript is not determined by the RQ-PCR (real-time quantitative polymerase chain reaction) method.

Treatment options for chronic myeloid leukemia

In order to achieve cytoreduction,
- during pregnancy to maintain a hematological response,
- in cases of resistance and / or intolerance to interferon or TKI preparations,
- if it is impossible to perform allo-HSCT,
- when it is impossible to provide patients with CML with a sufficient amount of TKI.

The usual therapy for HU is to prescribe this drug at a dose of 2-3.0 grams per day in combination with allopurinol at a daily dose of 600-800 mg with sufficient hydration. The dose is corrected depending on the degree of decrease in the level of leukocytes, when they decrease below 10.0x10 9 /l, they switch to a maintenance dose of 0.5 g / day with or without allopurinol. It is desirable to maintain the number of leukocytes at a level not higher than 6-8.0x10 9 /l.

In the event of a decrease in the number of leukocytes below 3.0x10 9 /l, the drug is temporarily stopped. Tolerability of the drug is quite good, but with prolonged use, the formation of stomach ulcers is possible.

The introduction of rINF preparations into practice made it possible to obtain in some CML patients not only long-term clinical and hematological, but also cytogenetic remission, although the frequency complete cytogenetic response (CCyR) was low - 1015%. The combination of rINF+LDAC drugs slightly increased the frequency of CCyR (25-30%), but sooner or later the disease progressed in almost all patients of this group.

Method of treatment with rINF drugs

1st week: 3 million U / m2 subcutaneously daily,
- 2nd and 3rd weeks: 5 million U/m subcutaneously daily,
- in the future, the drug is prescribed at 5 million U / m subcutaneously daily or 3 times a week.

The drug may cause allergic reactions, fever, skin itching, muscle pain (usually at the beginning of use). Therapy usually continues for 2 years, then there is a withdrawal from the control of the drug.

With the combination of rINF+LDAC (cytosar 20 g/m2 s.c. twice daily for 10 days monthly), the cytogenetic response was higher than with rINF alone, but there was no difference in overall survival.

A comparison of the results of using rINF at a dose of 3 million U/m 3 times a week and at a dose of 5 million U/m daily showed that low doses were as effective as high doses, but better tolerated. However, in all patients on such therapy, the presence of minimal residual disease was determined, which suggests the inevitability of relapse.

In routine clinical practice, sequential or combined use of IM or new TKIs with rINF preparations is not yet recommended, since the results of ongoing clinical trials are unknown. Currently, the use of rINF can be recommended in the same cases in which hydroxyurea therapy is recommended.

Conducting allo-HSCT as first-line therapy in the presence of an HLA-compatible donor, as well as the age of the patient below 50-55 years, has become a standard recommendation for patients with initially diagnosed CML since the early 1990s. Allo-HSCT is considered the only method that can completely eliminate the leukemic clone of cells from the body.

However, there are several problems that limit its widespread use in patients with CML:

The predominance in the population of patients with CML in the age group of 50-60 years,
- the impossibility for most patients to find an HLA-compatible related or not related donor,
- mortality up to 20% in the early post-transplantation period from complications polychemotherapy (PCT) or graft-versus-host disease (GVHD).

In FA, the decision to conduct allo-HSCT should be made taking into account the following data:

Assessment of the risk of progression of chronic myeloid leukemia (according to the Sokal index),
- determination of the effectiveness of TKI taking into account cytogenetics and PCR data,
- risk assessment of transplant and post-transplant complications,
- availability of an available donor.

According to the recommendations of the EBMT, in CML, allo-HSCT in HF, in FA or in late CP is indicated from a related or unrelated compatible donor, not from an unrelated incompatible donor; the problem of performing auto-HSCT is under development. In the CD phase, allo- or auto-HSCT is not indicated.

If a decision is made to perform allo-HSCT, the question arises of which conditioning regimen to offer the patient: myeloablative or non-myeloablative. One of the myeloablative regimens for allo-HSCT in CML patients is BuCy: busulfan at a dose of 4 mg/kg of body weight per day and cyclophosphamide 30 mg/kg of body weight per day for 4 days before allo-HSCT.

The non-myeloablative (reduced) regimen of Bu-Flu-ATG consists of a single dose of a combination of busulfan at a dose of 8 mg/kg of body weight, fludarabine 150 mg/m and rabbit antithymocyte globulin at a dose of 40 mg. However, due to the lack of randomized trials, this option is not recommended as a standard of care.

Role Awareness tyrosine kinase activity (TKA) BCR-ABL protein during myeloproliferation led to the synthesis of a new series of drugs targeting BCR-ABL encoded proteins. Inhibition of TKA leads to the interruption of signals that control the leukemic phenotype. The first of the TKA inhibitors, imatinib mesylate (IM), has a high and relatively specific biochemical activity in CML, which has led to its rapid introduction into clinical practice.

With the advent of TKI, indications for allo-HSCT have changed dramatically. In early CP CML, allo-HSCT is indicated in the development of resistance or intolerance to TKI, so its implementation in adult patients as a first-line therapy is not recommended today.

However, there are two exceptions to this rule:

In pediatric practice, it is preferable to use allo-HSCT as primary therapy in the presence of an HLA-compatible related donor,
- if the cost of the proposed TKI treatment significantly exceeds the cost of allo-HSCT.

In general, the majority of patients with CML in HF should be treated with initial MI if possible.

Imatinib mesylate (IM)- Gleevec, which is a tyrosine kinase inhibitor, was used in the clinic in 1995. IM (2-phenylaminopyrimidine) effectively blocks the kinase activity of the BCR-ABL protein and can block other proteins with protein kinase activity necessary for normal cell survival.

Studies have shown that IM selectively inhibits cell proliferation in chronic myeloid leukemia. The drug is mainly eliminated by the liver, a 50% decrease in its plasma concentration is about 18 hours. The recommended starting dose of the drug is 400 mg / day, which allows you to achieve Pcomplete clinical and hematological remission (CHR) in 95% and CCyR in 76% of cases. In the group of patients with CCyR major molecular remission (MMolR) was determined only in 57% of cases.

The use of MI in "late" CP at the same dosage allows to achieve CCyR in 41-64% with progression-free survival in 69% of patients. With the use of IM in FA at a dose of 600 mg/day, CHR was achieved in 37%, CCyR in 19% of cases and three-year PFS in 40% of patients. With the use of MI at the same dose in CD CML, CHR was achieved in 25%, PFS was less than 10 months, overall survival over 3 years was in 7% of cases.

Since the frequency of CCyR is very high in patients treated for MI, it is necessary to measure the level of the BCR-ABL transcript to determine the presence minimal residual disease (MRD). The frequency of the absence of this transcript is considered as CMolR, is very variable and ranges from 4-34%. It has been shown that Ph+ stem cells are less sensitive to MI than late Ph+ progenitors.

In case of suboptimal effect from the use of MI in CP at a dose of 400 mg/day, it is proposed to escalate the dose of the drug to 600-800 mg/day, provided that resistance to MI is not associated with additional BCR-ABL mutations. Taking MI at a dose of 600 mg per day is significantly more effective in FA and BC. In CP patients with hematological and cytogenetic resistance to MI at a dose of 400 mg/day, increasing the MI dose to 800 mg per day caused CHR in 65% and CCyR in 18% of patients.

When using MI, some complications can be observed:

Anemia and/or pancytopenia
- infraorbital edema, rarely - generalized edema,
- pain in the bones and joints,

- decrease in the level of calcium and phosphorus in the blood,
- skin itching.

To date, there are two drugs of the TKI group that are registered for use as 2nd-line drugs for the treatment of CML in cases of development of resistance to MI: dasatinib and nilotinib.

Dasatinib (Sprycel) is an inhibitor of ABL kinases (it inhibits about 50 kinases in total) and differs from IM in that it can bind both active and inactive (open and closed) conformations of the ABL kinase domain, and also inhibits the Src family of kinases, including Srk and Lyn.

It can be considered as a dual inhibitor. Dasatinib is 300-fold more potent than IM and is also active against most IM-resistant mutant subclones, with the exception of clone T315I and probably the mutant clone F317L. The drug is used to treat CML patients with resistance or intolerance to MI. Remission was observed to the same extent in patients with and without kinase mutations, except for T315I mutations.

The drug can cause complications in the form of neutropenia, thrombocytopenia, vomiting, diarrhea, gastrointestinal bleeding, generalized edema, skin rashes, hypertension, COPD. In single patients, pleural and pericardial effusion may be observed. To correct complications, you should take a break in taking the drug, prescribe diuretics, corticosteroids, and, if necessary, thoracocentesis.

The 100 mg dose once daily is comparable in efficacy to 70 mg twice daily but is better tolerated.

Nilotinib (Tasigna) is an aminopyrimidine derivative, ie. modified derivative of IM, which explains their similar spectrum of inhibition (inhibits four TCs). The drug has an increased ability to bind the ATP region of the BCR-ABL oncoprotein. It is 20-50 times more effective than IM against IM-sensitive leukemic cells, and is also active against all IM-resistant cell lines with mutations in the kinase ABL domain, with the exception of the T315I mutation and, probably, the Y253H mutant clone.

In the group of patients in CP CML resistant to MI, CHR was achieved in 71% and CCyR in 48% of patients. Overall 2-year survival in this group was 95%. There were no differences in the number of remissions in patients with or without a mutation in the ABL kinase domain. When using the drug in FA, one month after the start of therapy, CHR was registered in 55% of cases, overall survival after 12 months was 82%. In the CD phase, with 12 months of therapy, overall survival was 47%.

skin itch,
- constipation,
- level up liver enzymes,
- increase in the level of indirect bilirubin,
- rashes on the skin.

For dasatinib, a 50% reduction in plasma levels is 3-5 hours, for nilotinib and MI, 15-18 hours. For dasatinib, long-term inhibition of the BCR-ABL protein does not necessarily mean the elimination of leukemic cells in chronic myeloid leukemia. Therefore, the postulate about the prevalence of the effectiveness of long-term inhibition of kinases in the treatment of CML is not applicable to dasatinib.

In general, dasatinib and nilotinib have approximately equal potency in patients with no response to MI therapy. However, none of them is recommended for use in patients with the N315I mutant clone.

In stage clinical trials is the drug bosutinib, which inhibits ABL and Srk kinases, and therefore is a dual kinase inhibitor. It is active against cell lines carrying mutations in three of the four kinase domains. However, it should be borne in mind that the use of the above drugs does not provide a complete cure.

After the use of imatinib, in case of development of resistance to the drug, with its intolerance or severe complications, patients should be offered TKI therapy of the 2nd line of therapy;
- the choice of drug should be determined by the degree of its toxicity.

Allo-HSCT is offered for:

The presence of T315I mutations and other mutations
- no effect in the treatment of TKI in FA and BC,
- no effect in the treatment of TKI of the 2nd line of therapy.

Chronic myeloid leukemia is a process of mutation of pluripotent cells, and further uncontrolled reproduction of granulocytes. According to statistics, myeloid leukemia accounts for 16% of all hemoblastoses of the middle age group of people, and 8% of all other age groups. The disease usually manifests itself after 31 years, and the peak of activity occurs at 45 years. Children under 12 rarely get sick.

Chronic myeloid leukemia equally affects the body of a man or woman. It is difficult to recognize the course of the disease, because. The process is initially asymptomatic. Often, myeloid leukemia is detected in the later stages, and then the survival rate is reduced.

According to ICD-10, the disease has a classification: C 92.1 - Chronic myelocytic leukemia.

Causes of Chronic Myeloid Leukemia

The pathogenesis of myeloid leukemia originates in myelosis. In the course of certain factors, a tumorigenic clone of the cell appears, which is able to differentiate into white blood cells responsible for maintaining immunity. This clone actively reproduces in the bone marrow, excluding useful hematopoietic sprouts. The blood is saturated with neutrophils in equal amounts with erythrocytes. Hence the name - leukemia.

The human spleen should act as a filter for these clones, but due to their large number, the organ cannot cope. The spleen is pathologically enlarged. The process of metastasis formation and spread to neighboring tissues and organs begins. Appears acute leukemia. There is damage to the liver tissues, heart, kidneys and lungs. Anemia intensifies, and the condition of the body leads to death.

Experts have found that CML is formed under the influence of the following factors:

• Exposure to radiation.
• Viruses.
• electromagnetic fields.
• Chemical substances.
• Heredity.
• Reception of cytostatics.

Stages of development of pathology

It is customary to distinguish three main stages of the disease:

1. Initial - due to a slight overgrowth of the spleen, as well as an increase in leukocytes in the blood. At this stage, patients are monitored, without prescribing a specific treatment.
2. Expanded - dominate Clinical signs. The patient is prescribed specialized drugs. Myeloid tissue, located in myelosis and in the spleen, increases. Rarely, the lesion affects lymphatic system. Sprawl is happening connective tissue in the bone marrow. Severe liver infiltration. The spleen thickens. When touched, intense pain occurs. After an infarction of the spleen, noises of friction of the peritoneum against the affected area are heard. Possible increase in temperature. High probability of damage to neighboring organs: stomach ulcer, pleurisy, eye hemorrhage or pneumonia. Great amount uric acid, formed during the breakdown of neutrophils, contributes to the formation of stones in the urinary tract.
3. Terminal - there is a decrease in the level of platelets, anemia develops. There are complications in the form of infections and bleeding. Leukemoid infiltration causes damage to the heart, kidneys, and lungs. The spleen occupies most of the abdominal cavity. Dense, painless, raised bumps appear on the skin. pink spots. This is what a tumor infiltrate looks like. Lymph nodes increase due to the formation of tumors in them like sarcomas. Sarcoid-type tumors can appear and develop in any organ or even bones of a person. There are signs of subcutaneous hemorrhage. A high content of leukocytes provokes the development of hyperleukocytosis syndrome, in which the central nervous system is damaged. Also observed mental disorders and blurred vision due to swelling of the optic nerve.

A blast crisis is an acute worsening of myelogenous leukemia. The condition of the patients is grave. Most spend time in bed, unable to even roll over. Patients are severely malnourished and may suffer from severe bone pain. The skin becomes bluish in color. Lymph nodes are stony, enlarged. The organs of the abdominal cavity, the liver and spleen, reach their maximum size. The strongest infiltration affects all organs, causing failure, leading to death.

Symptoms of the disease

The chronic period lasts on average up to 3 years, isolated cases - 10 years. During this time, the patient may not be aware of the presence of the disease. Unobtrusive symptoms, such as fatigue, decreased ability to work, a feeling of a full stomach, are rarely given importance. On examination, the spleen is enlarged and granulocytes are elevated.

In the early stages of CML, there may be a decrease in hemoglobin in the blood. There is normochromic anemia. The liver in chronic myeloid leukemia is enlarged, as is the spleen. There is an enlargement of erythrocytes. In case of absence medical supervision the disease accelerates its development. The transition to the deterioration phase can be indicated either by tests or by the general condition of the patient. Patients quickly get tired, suffer from frequent dizziness, bleeding becomes more frequent, which is difficult to stop.

The ongoing treatment in the later stages does not reduce the level of leukocytes. The appearance of blast cells is observed, there is a change in their functions (a characteristic phenomenon for a malignant tumor). In patients with CML, appetite is reduced or completely absent.

Diagnostic measures

The specialist conducts a thorough examination of the patient and writes down the anamnesis in the medical history. Next, the doctor prescribes clinical tests and other blood tests. The first indicator is an increase in granulocytes. For more accurate diagnosis a small amount of bone marrow is taken and histological studies are carried out.

The final point in the diagnosis is the study of the polymerase chain reaction with reverse transcription for the presence of the Philadelphia chromosome.

Chronic myeloid leukemia can be confused with diffuse myelosclerosis. For an accurate determination, an x-ray examination is performed, for the presence or absence of areas of sclerosis on flat bones.

How is myeloid leukemia treated?

Treatment of chronic myeloid leukemia is carried out in the following ways:

• Bone marrow transplantation.
• Irradiation.
• Chemotherapy.
• Resection of the spleen.
• Removal of leukocytes from the blood.

Chemotherapy is carried out with such drugs as: Sprycel, Mielosana, Glivec, etc. The most effective method considered a bone marrow transplant. After the transplant procedure, the patient must be in the hospital under the supervision of doctors, because. such an operation destroys the entire immunity of a person. After a while, complete recovery occurs.

Chemotherapy is often supplemented with radiation if it does not have the desired effect. Gamma radiation affects the area where the diseased spleen is located. These rays prevent the growth of abnormally developing cells.

If it is impossible to restore the function of the spleen, it is resected during the blast crisis. After operation general development pathology slows down, and drug treatment enhances efficiency.

The leukapheresis procedure is carried out with the highest level of leukocytes. The procedure is similar to plasmapheresis. With the help of a special apparatus, all leukocytes are removed from the blood.

Life expectancy in chronic myeloid leukemia

The majority of patients die in the second or third stage of the disease. Approximately 8-12% die after chronic myeloid leukemia is diagnosed in the first year. After the final stage, survival is 5-7 months. In the case of a positive outcome after the terminal stage, the patient can last about a year.

According to statistics, the average life expectancy of patients with CML in the absence of the necessary treatment is 2-4 years. The use of cytostatics in the treatment prolongs life up to 4-6 years. Bone marrow transplantation prolongs life much more than other treatments.

- a malignant myeloproliferative disease characterized by a predominant lesion of the granulocytic germ. May be asymptomatic for a long time. It is manifested by a tendency to low-grade fever, a feeling of fullness in the abdomen, frequent infections and an enlarged spleen. Anemia and changes in platelet levels are observed, accompanied by weakness, pallor, and increased bleeding. In the final stage, fever, lymphadenopathy and skin rash. Diagnosis is based on history, clinical picture and data laboratory research. Treatment - chemotherapy, radiotherapy, bone marrow transplantation.

General information

Chronic myeloid leukemia - oncological disease resulting from a chromosomal mutation with damage to pluripotent stem cells and subsequent uncontrolled proliferation of mature granulocytes. It accounts for 15% of the total number of hemoblastoses in adults and 9% of total number leukemia in all age groups. Usually develops after 30 years, the peak incidence of chronic myeloid leukemia occurs at the age of 45-55 years. Children under 10 years of age are extremely rare.

Chronic myeloid leukemia is equally common in women and men. Due to an asymptomatic or oligosymptomatic course, it can become an incidental finding when examining a blood test taken in connection with another disease or during a routine examination. In some patients, chronic myeloid leukemia is detected in the final stages, which limits the possibilities of therapy and worsens survival rates. Treatment is carried out by specialists in the field of oncology and hematology.

Etiology and pathogenesis of chronic myeloid leukemia

Chronic myelogenous leukemia is considered the first disease in which a link between the development of pathology and a specific genetic disorder has been reliably established. In 95% of cases, the confirmed cause of chronic myeloid leukemia is a chromosomal translocation known as the "Philadelphia chromosome". The essence of translocation is the mutual replacement of sections of chromosomes 9 and 22. As a result of this replacement, a stable open reading frame is formed. The formation of a frame causes an acceleration of cell division and suppresses the DNA repair mechanism, which increases the likelihood of other genetic abnormalities.

Among the possible factors contributing to the appearance of the Philadelphia chromosome in patients with chronic myeloid leukemia, ionizing radiation and contact with certain chemical compounds are called. The mutation results in enhanced proliferation of pluripotent stem cells. In chronic myeloid leukemia, predominantly mature granulocytes proliferate, but the abnormal clone also includes other blood cells: erythrocytes, monocytes, megakaryocytes, less often B- and T-lymphocytes. Ordinary hematopoietic cells do not disappear, and after the suppression of the abnormal clone, they can serve as the basis for normal proliferation. blood cells.

Chronic myeloid leukemia is characterized by a staged course. In the first, chronic (inactive) phase, there is a gradual aggravation of pathological changes while maintaining a satisfactory general condition. In the second phase of chronic myeloid leukemia - the acceleration phase, the changes become apparent, progressive anemia and thrombocytopenia develop. The final stage of chronic myeloid leukemia is a blast crisis, accompanied by rapid extramedullary proliferation of blast cells. Lymph nodes, bones, skin, central nervous system, etc. become the source of blasts. severe complications ending in the death of the patient. In some patients, the acceleration phase is absent, the chronic phase is immediately replaced by a blast crisis.

Symptoms of Chronic Myeloid Leukemia

The clinical picture is determined by the stage of the disease. The chronic phase lasts an average of 2-3 years, in some cases up to 10 years. This phase of chronic myeloid leukemia is characterized by an asymptomatic course or the gradual appearance of “mild” symptoms: weakness, some malaise, decreased ability to work, and a feeling of abdominal fullness. An objective examination of a patient with chronic myeloid leukemia may reveal an enlarged spleen. According to blood tests, an increase in the number of granulocytes up to 50-200 thousand / μl with an asymptomatic course of the disease and up to 200-1000 thousand / μl with “mild” signs is revealed.

On the initial stages chronic myelogenous leukemia, some decrease in hemoglobin levels is possible. Subsequently, normochromic normocytic anemia develops. When examining a blood smear of patients with chronic myeloid leukemia, there is a predominance of young forms of granulocytes: myelocytes, promyelocytes, myeloblasts. There are deviations from the normal level of granularity in one direction or another (abundant or very scarce). The cytoplasm of cells is immature, basophilic. Anisocytosis is determined. In the absence of treatment, the chronic phase passes into the acceleration phase.

The beginning of the acceleration phase of chronic myeloid leukemia may be indicated by both a change in laboratory parameters and a deterioration in the condition of patients. There may be an increase in weakness, an enlarged liver, and a progressive enlargement of the spleen. In patients with chronic myeloid leukemia, clinical signs of anemia and thrombocytopenia or thrombocytosis are detected: pallor, fatigue, dizziness, petechiae, hemorrhage, increased bleeding. Despite ongoing treatment, the number of leukocytes gradually increases in the blood of patients with chronic myeloid leukemia. At the same time, there is an increase in the level of metamyelocytes and myelocytes, the appearance of single blast cells is possible.

The blast crisis is accompanied by sharp deterioration condition of a patient with chronic myeloid leukemia. New chromosomal abnormalities, a monoclonal neoplasm is transformed into a polyclonal one. There is an increase in cellular atypism with the inhibition of normal hematopoietic sprouts. Pronounced anemia and thrombocytopenia are observed. The total number of blasts and promyelocytes in the peripheral blood is more than 30%, in the bone marrow - more than 50%. Patients with chronic myeloid leukemia lose weight and appetite. There are extramedullary foci of immature cells (chloroma). Bleeding and severe infectious complications develop.

Diagnosis of chronic myeloid leukemia

The diagnosis is established on the basis of the clinical picture and the results of laboratory tests. The first suspicion of chronic myelogenous leukemia often occurs with an increase in the level of granulocytes in the general blood test, prescribed as a preventive examination or examination in connection with another disease. Data can be used to clarify the diagnosis. histological examination material obtained by sternal puncture of the bone marrow, however, the final diagnosis of "chronic myeloid leukemia" is made when the Philadelphia chromosome is detected using PCR, fluorescent hybridization, or cytogenetic studies.

The question of the possibility of making a diagnosis of chronic myeloid leukemia in the absence of the Philadelphia chromosome remains debatable. Many researchers believe that such cases can be explained by complex chromosomal disorders, due to which the identification of this translocation becomes difficult. In some cases, the Philadelphia chromosome can be detected using reverse transcription PCR. At negative results studies and an atypical course of the disease usually do not speak of chronic myeloid leukemia, but of an undifferentiated myeloproliferative / myelodysplastic disorder.

Treatment of chronic myeloid leukemia

The tactics of treatment are determined depending on the phase of the disease and the severity clinical manifestations. In the chronic phase, with an asymptomatic course and mild laboratory changes, they are limited to restorative measures. Patients with chronic myeloid leukemia are advised to observe the regime of work and rest, eat food rich in vitamins, etc. With an increase in the level of leukocytes, busulfan is used. After normalization of laboratory parameters and reduction of the spleen, patients with chronic myeloid leukemia are prescribed maintenance therapy or a course of treatment with busulfan. Radiotherapy is commonly used for leukocytosis associated with splenomegaly. With a decrease in the level of leukocytes, a pause is made for at least a month, and then they switch to maintenance therapy with busulfan.

In the progressive phase of chronic myeloid leukemia, it is possible to use a single chemotherapy drug or polychemotherapy. Mitobronitol, hexaphosphamide, or chloroethylaminouracil are used. As in the chronic phase, intensive therapy is carried out until laboratory parameters stabilize, and then they are switched to maintenance doses. Courses of polychemotherapy for chronic myeloid leukemia are repeated 3-4 times a year. In blast crises, treatment with hydroxycarbamide is carried out. With the ineffectiveness of therapy, leukocytapheresis is used. With severe thrombocytopenia, anemia, thromboconcentrate and erythrocyte mass transfusions are performed. With chloromas, radiotherapy is prescribed.

Bone marrow transplantation is carried out in the first phase of chronic myeloid leukemia. Long-term remission can be achieved in 70% of patients. If indicated, splenectomy is performed. Emergency splenectomy is indicated for rupture or threat of rupture of the spleen, planned - for hemolytic crises, "wandering" spleen, recurrent perisplenitis and pronounced splenomegaly, accompanied by dysfunction of the abdominal organs.

Prognosis of chronic myelogenous leukemia

The prognosis for chronic myeloid leukemia depends on many factors, the decisive of which is the moment of initiation of treatment (in the chronic phase, the activation phase or during the blast crisis). As unfavorable prognostic signs of chronic myeloid leukemia, a significant increase in the liver and spleen is considered (the liver protrudes from under the edge of the costal arch by 6 cm or more, the spleen by 15 cm or more), leukocytosis over 100x10 9 /l, thrombocytopenia less than 150x10 9 /l , thrombocytosis more than 500x10 9 /l, an increase in the level of blast cells in the peripheral blood up to 1% or more, an increase in the total level of promyelocytes and blast cells in the peripheral blood up to 30% or more.

The likelihood of a poor outcome in chronic myelogenous leukemia increases as the number of symptoms increases. The cause of death is infectious complications or severe hemorrhages. The average life expectancy of patients with chronic myeloid leukemia is 2.5 years, however, with timely initiation of therapy and a favorable course of the disease, this figure can increase to several decades.

Chronic myeloid leukemia is a blood disease of tumor etiology. With its development, uncontrolled growth and reproduction of all germ blood cells is observed. Pathological changes in one of the chromosomes cause the formation of a mutated gene, which causes a violation of hematopoiesis in the red bone marrow and, as a result, - enhanced growth cells.

The International Classification of Diseases of the Tenth Revision (ICD 10) assigns the code C92 to the disease. It can occur in 3 forms, depending on the stage. Taking into account how timely chronic myeloid leukemia was diagnosed, the maximum life expectancy of the patient is determined.

Reasons for development

The growth and functioning of healthy cells in the body occurs on the basis of the information that the chromosomes contain. When a particular cell divides, it creates a new copy of the DNA in the chromosomes. If such a division process is disturbed, mutating genes can be formed, which affect the development of oncological pathologies.

In the human body there are genes that stimulate the process of cell development - oncogenes. It also contains genes that slow down their growth, which is necessary for cell death at the right time - suppressors. When the activity of such genes is disturbed, healthy cells degenerate into oncological ones and suppressors are turned off from this process.

Modern medicine does not have enough specific information about why chronic myeloid leukemia develops, including acute. This issue is under study. There are suggestions that some predisposing factors influence the development of the disease:

1. Effects on the body of radioactive irradiation. Proof of this can be called the case of Nagasaki and Hiroshima. The medical history (ICD 10 - C92) of the Japanese in the area of ​​the accident states that most of them were susceptible to the development of chronic myeloid leukemia.
2. Viral damage to the body, as well as electromagnetic rays and chemicals that affect the body. Such a factor as a potential cause of the development of the disease is still being considered by researchers today.
3. hereditary predisposition. People suffering from congenital chromosomal abnormalities are in the zone increased risk incidence of myeloid leukemia. In most cases, these are people who have been diagnosed with Down syndrome or Klinefelter syndrome.
4. Treatment of tumor-like neoplasms certain medicines by the type of cytostatics in combination with radiation.

All such predisposing factors cause a structural disorder of cellular chromosomes in the red bone marrow and the formation of new DNA with an abnormal structure. At the same time, the number of the latter begins to increase so much that they crowd out healthy cells. At this time, uncontrolled growth of abnormal cells, similar to cancer cells, is observed.

Stages of development of the disease

Most people (about 80%) go to the hospital already at the time when the disease progresses to chronic course. At this time, there are slightly pronounced symptoms of myeloid leukemia, which are often confused with ordinary overwork: general malaise, decreased ability to work, increased sweating.

The chronic form of the disease can be asymptomatic for 2-3 months, and sometimes much longer - up to several years. In some cases, myelogenous leukemia is diagnosed quite by accident, by conducting a blood test to detect a different pathology in the body.

Chronic myeloid leukemia may be accompanied by complications in the form of an increase in overall temperature up to high performance, pain syndrome in the region of the left hypochondrium, etc. In the presence of complications, this form of the disease develops over 4 years or more.

If you do not start timely treatment of the disease of the chronic stage, it goes into stage 2 - acceleration. Immature leukocytes are intensively produced, reaching a volume of 10-19%. This stage lasts for about a year. At this stage of development, another symptomatology joins, which aggravates the general condition of the patient: anemia develops, the spleen enlarges, and medications, used in treatment, do not bring the same efficiency as at the initial stage of the development of the disease.

If you do not start treatment at the acceleration stage, the disease passes into the terminal stage, the pathogenesis of which is characterized by an increase in the number of malignant cells in the bone marrow and total absence it contains healthy cells. In this case, the outcome is the least favorable and the treatment prescribed by the doctor often turns out to be ineffective.

Symptoms

Chronic myelocytic leukemia (CML) can have different symptoms, depending on the stage at which the disease develops. Symptoms common to all stages include:

• severe general malaise;
• weight loss;
• decrease or complete loss of appetite (depending on the stage of the disease);
• the spleen and liver in chronic myeloid leukemia increase;
• blanching of the skin;
• pain syndrome in the bones;
• increased sweating.

If we consider the clinic of the disease, taking into account its stage, it looks like this:

1. Chronic: rapid satiety during meals, pain in the left hypochondrium, shortness of breath and a feeling of lack of air during physical activity, headache, disturbance visual function. Men may experience prolonged painful erections.
2. Acceleration stage. At this stage, progressive anemia develops, general pathological symptoms increase in intensity, pathological leukocyte cells are at an elevated level in the blood.
3. Terminal. The general condition of the patient worsens to critical indicators. There is a febrile syndrome, the general temperature rises to a maximum mark. Also, the development of terminal myelosis is characterized by bleeding through the mucous membranes, skin, intestines. Due to the increase in the spleen and hepatic lobes, pain occurs in the left hypochondrium and a feeling of heaviness.

Diagnostics

On the different stages development of the disease requires a specific diagnosis. At the initial stage of the course, appoint:

1. Carrying out a general blood test. The study helps to identify a slight decrease in blood components: hemoglobin and red blood cells. Often their level remains normal at this stage of the disease. You can detect the presence of moderate thrombocytosis, basophilia, eosinophilia. The blood picture in chronic myeloid leukemia shows leukocytosis with indicators of 15-30 * 109 / l.
2. Holding biochemical analysis . Diagnosis shows an increase in the amount of uric acid in the body.
3. Conducting a sternal puncture of the bone substance. Megakaryocytes are exceeded in their level of content, as well as granulocytic cells of young forms.

At the acceleration stage, it is necessary to carry out the following diagnostic measures:

At the terminal stage, pathology can be detected by:

1. Complete blood count, which helps to detect a critical decrease in the volume of red blood cells, platelets and hemoglobin, an increase in the volume of basophils up to 20%. Leukocytosis reaches 500-1000 * 109 / l.
2. Sternal puncture, which helps to identify a critical increase in the content of malignant cells in the medulla, as well as basophils and eosinophils.
3. Cytogenetic analysis, which helps to identify the presence of the Philadelphia chromosome in the body.

How to treat the disease

Myeloid blood disease requires specific treatment, the type of which is determined taking into account the stage of the course. In the event that the clinic of the disease is not very pronounced or is completely absent, compliance is prescribed proper diet food, reception vitamin preparations, carrying out general strengthening procedures. In this case, systematic monitoring by the attending physician is required.

If pronounced symptoms have joined, cytostatic drugs that block the growth of pathological cells are prescribed. Despite the high effectiveness of drugs, they can cause side effects: nausea, general malaise, loss hairline, inflammation of the stomach or intestines.

In severe cases, bone marrow transplantation and blood transfusion are performed. Sometimes such treatment helps to permanently save a person from the disease. The only condition is the complete compatibility of the donor substance with the patient's bone marrow.

Folk remedies in the treatment of chronic leukemia will not be effective. These are used only to strengthen human immunity and increase the body's defenses. Excellent medication in the treatment of the disease, Gleevec is considered, with the help of which it is possible to cause hematological remission of the pathology. The substances that make up the drug block and destroy the Philadelphia chromosome.

In an extremely severe case, a complete resection (removal) of the spleen is necessary, which improves the general condition of the patient and increases the effectiveness of the therapy.