Myeloid leukemia - what is it? Chronic myeloid leukemia: causes, treatment, prognosis. Chronic myeloid leukemia - life expectancy at different stages of the disease Chronic myeloid leukemia stages of the disease
18.02.2017
Oncological diseases often affect the circulatory system. One of the dangerous conditions is chronic myeloid leukemia, which is a blood cancer.
The disease is accompanied by chaotic proliferation of blood cells. More often the disease is diagnosed in men aged 30-70 years. In children and women, the disease occurs much less frequently, however, the possibility of the disease cannot be completely excluded.
CML is a tumor composed of myeloid cells. The nature of the disease is clonal; among other hemoblastoses, the disease accounts for up to 9% of cases. The course of the disease may not manifest itself with special symptoms at first. To diagnose this condition, you need to take a blood smear and bone marrow sample for analysis. Myeloid leukemia is characterized by an increased number of granulocytes (a type of white blood cell) in the blood. These leukocytes are formed in the bone marrow red matter and enter the bloodstream in an immature form. At the same time, the number of normal white blood cells decreases. The doctor can see this picture in the results of blood tests.
Causes of myeloid leukemia
Scientists have not yet fully established the etiology of the disease, but it has been established that chronic myeloid leukemia can be provoked by the following factors:
- exposure to radiation. The relationship between radiation and oncology can be proven by examples of the Japanese who were in Hiroshima and Nagasaki during the explosion of the atomic bomb. Subsequently, many of them were diagnosed with the development of chronic myeloid leukemia;
- influence of chemicals, electromagnetic radiation, viruses. The theory is controversial in the scientific community and has not yet received scientific recognition;
- heredity. According to research, the risk of developing myeloid leukemia is greater in people with chromosomal disorders (Down syndrome, Klinefelter syndrome, etc.);
- treatment with certain medications that are intended for the treatment of tumors against the background of radiation. Aldehydes, alkenes, alcohols, and tobacco smoking also increase the risk of getting sick. This is another reason to think that a healthy lifestyle is the only right choice for a sane person.
Due to the fact that the structure of the red cell chromosomes in the bone marrow is disrupted, new DNA appears, the structure of which is abnormal. Next, the abnormal cells are cloned, gradually displacing normal cells, until the situation when the number of abnormal clones begins to greatly predominate. As a result, abnormal cells multiply and grow in number uncontrollably, just like cancer cells. They do not obey the traditional mechanism of natural death.
When they enter the bloodstream, abnormal white blood cells do not perform their main task, leaving the body without protection. Therefore, a person who develops chronic myeloid leukemia becomes susceptible to allergies, inflammation, etc.
Phases of myeloid leukemia
Chronic myeloid leukemia develops gradually, sequentially passing through 3 important phases, which can be found out below.
The chronic phase lasts about 4 years. It is at this time that the patient usually consults a doctor. In the chronic stage, the disease is characterized by stability, so minimal symptoms may practically not bother a person. It happens that the disease is discovered by chance during the next blood test.
The acceleration phase lasts about one and a half years. At this time, the pathological process is activated, the number of immature leukocytes in the bloodstream increases. With the right choice of therapy and timely response, the disease can be returned to the chronic phase.
The terminal phase (blast crisis) lasts less than six months and ends fatally. The stage is characterized by exacerbation of symptoms. At this time, red bone marrow cells are completely replaced by abnormal clones of a malignant nature.
Symptoms of myeloid leukemia
Depending on the stage of chronic myeloid leukemia at the moment, the symptoms will differ. However, it is possible to identify common features characteristic of the disease at different stages. Patients show obvious lethargy, weight loss, and loss of appetite. As the disease progresses, the spleen and liver enlarge and the skin becomes pale. Patients experience bone pain and excessive sweating at night.
As for the symptoms of each phase, for the chronic stage the characteristic signs will be: deterioration in health, loss of strength, weight loss. While eating, patients quickly feel full, and pain often occurs in the left abdominal area. Rarely in the chronic phase, patients complain of shortness of breath, headaches and visual disturbances. Men may experience prolonged, painful erections.
For the accelerated form, the characteristic signs will be: progressive anemia, the severity of pathological symptoms, the results of laboratory tests will show an increase in the number of leukocyte cells.
The terminal stage is characterized by worsening of the disease picture. A person often gets feverish for no obvious reason. The temperature can rise to 39 degrees, the person feels trembling. Bleeding through mucous membranes, skin, and intestines is possible. The person feels severe weakness and exhaustion. The spleen enlarges to its maximum, giving pain in the left side of the abdomen and a feeling of heaviness. As mentioned above, the terminal stage is followed by death. Therefore, it is better to start treatment as early as possible.
Diagnosis of myeloid leukemia
A hematologist can diagnose myeloid leukemia in a person. He conducts a visual examination, listens to complaints and sends the patient for an ultrasound of the abdomen and a blood test. Additionally, biochemistry, biopsy, bone marrow puncture, and cytochemical studies are performed. The blood picture in the test results will indicate the presence of the disease if:
- the proportion of myeloblasts in the blood or bone marrow fluid is up to 19%, basophils - over 20% (chronic phase);
- the proportion of myeloblasts and lymphoblasts exceeds 20%, bone marrow biopsy shows large accumulations of blasts (terminal phase).
Treatment of myeloid leukemia
The doctor determines exactly how to treat the disease, taking into account the stage of the disease, the presence of contraindications, concomitant diseases, and age. If the disease proceeds without any special symptoms, then for the treatment of such a condition as chronic myeloid leukemia, treatment is prescribed in the form of general strengthening agents, nutritional correction, taking vitamin complexes, and regular observation in a dispensary. According to scientists, a-interferon has a beneficial effect on the condition of patients.
As for the prescription of drugs, if the test results for leukocytes are 30-50*109/l, the patient is prescribed myelosan in an amount of 2-4 mg/day. When the indicators increase to 60-150*109/l, the dose of the drug increases to 6 mg/day. If leukocytosis exceeds the specified values, the daily dose of myelosan is increased to 8 mg. The effect will be noticeable approximately 10 days from the start of therapy. The hemogram will normalize against the background of a decrease in the size of the spleen during approximately 3-6 weeks of therapy, when the total dose of the drug will be 250 mg. Next, the doctor prescribes maintenance treatment by taking myelosan once a week at a dosage of 2-4 mg. You can replace maintenance treatment with regular courses of the drug in case of exacerbation of the process, if the number of leukocytes increases to 20-25*109/l against the background of an enlarged spleen.
Radiation therapy (radiation) is prescribed as the primary treatment in some cases when splenomegaly is the main symptom. Irradiation is prescribed only if the level of leukocytes in tests is above 100*109/l. As soon as the indicator drops to 7-20*109/l, irradiation is stopped. After about a month, body support with melosan is prescribed.
During the treatment of the progressive phase of chronic myeloid leukemia, mono- and poly-type chemotherapy is prescribed. If tests show significant leukocytosis, and myelosan does not have an effect, myelobromol is prescribed at 125-250 mg per day, monitoring peripheral blood parameters. After about 2-3 weeks, the hemogram normalizes, after which maintenance therapy can begin by taking myelobromol 125-250 mg every 7-10 days.
In case of severe splenomegaly, dopan is prescribed if other drugs and anti-leukemia drugs do not give the desired effect. In this case, dopan is taken 6-10 mg once every 4-10 days (as prescribed by a doctor). The interval between doses of the drugs will depend on the rate at which the number of leukocytes in the blood decreases and how the size of the spleen changes. As soon as the number of leukocytes decreases to 5-7*109/l, dopan can be discontinued. It is best to take the medication after dinner, and then take sleeping pills. This is due to the possibility of dyspeptic symptoms. For maintenance therapy, the doctor may prescribe dopam at a dosage of 6-10 mg every 2-4 weeks, monitoring the hemogram.
If doctors observe that the disease exhibits resistance to dopan, myelosan, myelobromol and radiation, then they prescribe hexaphosphamide to the patient. If the test results show the number of leukocytes reaches 100*109/l, then hexaphosphamide is prescribed 20 mg daily; if the reading is 40-60*109/l, it is enough to take 10-20 mg of the drug twice a week. As the number of abnormal leukocytes in the blood decreases, the doctor reduces the dosage of the drug, and as soon as the levels drop to 10-15 * 109/l, treatment with the drug is stopped. The course of treatment is usually calculated at a dose of the drug of 140-600 mg over 10-30 days. Positive results from treatment with the drug are usually observed after 1-2 weeks. If maintenance therapy is necessary, hexaphosphamide is prescribed 10-20 mg every 5-15 days. The doctor prescribes the intervals individually, taking into account the dynamics of treatment and the patient’s health condition.
For the treatment of the progressive phase of chronic myeloid leukemia, drug programs ABAMP and CVAMP are prescribed. The ABAMP program consists of two 10-day courses with a 10-day break. The list of drugs includes : cytosar (30 mg/m2 on days 1 and 8 intramuscularly), methotrexate (12 mg/m2 on days 2, 5 and 9 intramuscularly), vincristine (1.5 mg/m2 on days 3 and 10 intramuscularly), 6-mercaptopurine ( 60 mg/m2 every day), prednisolone (50-60 mg/day, if thrombocytopenia is less than 100*109/l). If the number of leukocytes exceeds 40*109/l, hyperthrombocytosis persists, then prednisolone is not prescribed.
The ABAMP program is a whole course of drugs similar to the previous program, but instead of Cytosar, cyclophosphamide is prescribed intramuscularly at 200-400 mg every other day. Polychemotherapy is carried out 3-4 times during the year, and in the intervals between courses, myelosan is prescribed according to the general scheme and 6-mercaptopurine (100 mg every day for 10 days with a 10-day break).
In the treatment of chronic myeloid leukemia, including blast crises, hydroxyurea is prescribed. It has contraindications: leukopenia (white blood cell count below 3*109/l) and thrombocytopenia (platelet count in tests less than 100*109/l). Initially, the drug is prescribed at 1600 mg/m every day. If leukocytes in the blood become less than 20*10/l, then the drug is prescribed at 600 mg/m2, and if the number of leukocytes drops to 5*109/l, the drug is discontinued.
In case of resistance to cytostatics and progression of myeloid leukemia, doctors can prescribe leukocytapheresis in parallel with one of the above polychemotherapy regimens. Indications for leukocytapharesis are clinical manifestations of stasis in the vessels of the brain (decreased hearing and pain in the head, a feeling of “hot flashes”, heaviness in the head) against the background of hyperthrombocytosis and hyperleukocytosis.
In the blast crisis stage, chemotherapy is prescribed, which is effective for acute leukemia. For anemia and infectious complications, transfusion of red blood cells, platelet concentrate and antibacterial therapy are prescribed.
If a patient is diagnosed with extramedullary tumor formations (tonsils covering the larynx, etc.) that threaten his life, then radiation therapy is prescribed.
Bone marrow transplantation is used in cases of chronic myeloid leukemia in the chronic phase. Thanks to transplantation, remission occurs in approximately 70% of patients.
Splenectomy in the case of chronic myeloid leukemia is prescribed for splenic rupture and a condition that is fraught with rupture. Indications may be: severe discomfort in the abdomen, which is associated with the huge size of the spleen, as well as pain syndrome due to repeated perisplenitis, deep thrombocytopenia, hemolytic crisis, syndrome of the “wandering” spleen with the risk of twisting of the leg.
Prognosis for chronic myeloid leukemia
The disease is a life-threatening condition. Most patients say goodbye to life at the accelerated and terminal stages of the disease. Up to 10% of patients diagnosed with myeloid leukemia die within 2 years. After the blast crisis phase, life expectancy can be up to six months.
If it is possible to achieve remission during the terminal phase, the patient's life can last up to a year. However, at any stage of the disease you should not give up. It is likely that the statistics do not include all cases where the disease was extinguished and the life with it was extended by several years, perhaps by decades.
There are many diagnoses whose names mean little to ordinary citizens. One such disease is chronic myeloid leukemia. Reviews from patients with this disease are nevertheless capable of attracting attention, since this disease can not only cause significant damage to health, but also lead to a fatal outcome.
The essence of the disease
If you hear a diagnosis such as “chronic myeloid leukemia,” then it is important to understand that we are talking about a serious tumor disease of the hematopoietic system, which affects the hematopoietic stem cells of the bone marrow. It can be classified as a group of leukemias, which are characterized by large formations of granulocytes in the blood.
At the very beginning of its development, myeloid leukemia manifests itself through an increase in the number of leukocytes, reaching almost 20,000/μl. Moreover, in the progressive phase this figure changes to 400,000/μl. It is worth noting the fact that both the hemogram and the myelogram show a predominance of cells with different degrees of maturity. We are talking about promyelocytes, metamyelocytes, band and myelocytes. In the case of the development of myeloid leukemia, changes are detected in the 21st and 22nd chromosomes.
This disease in most cases leads to a noticeable increase in the content of basophils and eosinophils in the blood. This fact is evidence that we are dealing with a severe form of the disease. In patients who suffer from such an oncological disease, splenomegaly develops, and a large number of myeloblasts are recorded in the bone marrow and blood.
How does the disease begin?
Chronic myeloid leukemia pathogenesis is quite interesting. Initially, a somatic mutation of a pluripotent hematopoietic blood stem cell can be identified as a trigger factor in the development of this disease. The main role in the mutation process is played by the cross-translocation of chromosomal material between the 22nd and 9th chromosomes. In this case, the Ph chromosome is formed.
There are cases (no more than 5%) when the Ph chromosome cannot be detected during a standard cytogenetic study. Although molecular genetic research reveals an oncogene.
Chronic myeloid leukemia can also develop due to exposure to various chemical compounds and radiation. Most often this disease is diagnosed in adulthood, extremely rarely in adolescents and children. As for gender, this type of tumor is recorded with equal frequency in both men and women aged 40 to 70 years.
Despite all the experience of doctors, the etiology of the development of myeloid leukemia is still not completely clear. Experts suggest that acute and chronic myeloid leukemia develops due to a disorder of the chromosomal apparatus, which, in turn, is caused by the influence of mutagens or hereditary factors.
Speaking about the effects of chemical mutagens, it is worth paying attention to the fact that quite a few cases have been recorded in which people exposed to benzene or using cytostatic drugs (Mustargen, Imuran, Sarcozoline, Leukeran, etc.) , myeloid leukemia developed.
Chronic myeloid leukemia: stages
With a diagnosis such as “myeloid leukemia,” three stages of development of this disease are distinguished:
Initial. Characterized by an enlarged spleen and a stable increase in leukocytes in the blood. The patient's condition is considered dynamically, without using radical treatment measures. The disease, as a rule, is diagnosed already at the stage of total generalization of the tumor in the bone marrow. At the same time, in the spleen, and in some cases in the liver, extensive proliferation of tumor cells is observed, which is characteristic of the advanced stage.
Expanded. Clinical signs at this stage begin to dominate, and the patient is prescribed treatment using specific drugs. At this stage, the myeloid tissue in the bone marrow, liver and spleen grows, and the fat in the flat bones is virtually completely replaced. There is also a sharp predominance of the granulocytic lineage and three-line proliferation. It is worth noting that in the advanced stage, lymph nodes are extremely rarely affected by the leukemic process. In some cases, myelofibrosis may develop in the bone marrow. There is a possibility of developing pneumosclerosis. As for the infiltration of the liver by tumor cells, in most cases it is quite pronounced.
Terminal. At this stage of the disease, thrombocytopenia and anemia progress. Manifestations of various complications (infection, bleeding, etc.) become obvious. The development of a second tumor from immature stem cells is often observed.
What life expectancy should you expect?
If we talk about people who have had to deal with chronic myeloid leukemia, it is worth noting that modern treatment methods have significantly increased the chances of such patients for a relatively long life. Due to the fact that discoveries have been made in the field of pathogenetic mechanisms of the development of the disease, which have made it possible to develop drugs that can act on the mutated gene, with a diagnosis such as chronic myeloid leukemia, the life expectancy of patients can be 30-40 years from the moment the disease is identified. But this is possible provided that the tumor was benign (slow enlargement of the lymph nodes).
In the case of the development of a progressive or classic form, the average is from 6 to 8 years from the moment the disease was diagnosed. But in each individual case, the number of years that the patient can enjoy is significantly influenced by the measures taken during the treatment process, as well as by the form of the disease.
On average, according to statistics, up to 10% of patients die within the first two years after detection of the disease and 20% in subsequent years. Many patients with myeloid leukemia die within 4 years after the diagnosis was made.
Clinical picture
The development of a disease such as chronic myeloid leukemia occurs gradually. At first, the patient feels a deterioration in his general health, fatigue, weakness, and in some cases moderate pain in the left hypochondrium. After the study, an enlarged spleen is often recorded, and a blood test reveals significant neutrophilic leukocytosis, characterized by a shift in the leukocyte count to the left due to the action of myelocytes with an increased content of basophils, eosinophils and platelets. When the time comes for the full picture of the disease, patients experience loss of ability to work due to sleep disturbances, sweating, a steady increase in general weakness, a significant increase in temperature, pain in the spleen and bones. There is also a loss of weight and appetite. At this stage of the disease, the spleen and liver are significantly enlarged.
At the same time, chronic myeloid leukemia, the symptoms of which differ depending on the stage of development of the disease, already in the initial stage leads to a predominance of eosinophils, granular leukocytes and basophils in the bone marrow. This growth occurs due to a decrease in other leukocytes, normoblasts and red blood cells. If the disease process begins to worsen, the number of immature myeloblasts and granulocytes increases significantly, and hemocytoblasts begin to appear.
Blast crisis in chronic myeloid leukemia leads to total metaplasia. In this case, there is a high fever, during which there are no signs of infection. Hemorrhagic syndrome develops (intestinal, uterine, mucous bleeding, etc.), leukemides in the skin, ossalgia, lymph nodes enlarge, complete resistance to cytostatic therapy and infectious complications are recorded.
If it was not possible to significantly influence the course of the disease (or such attempts were not made at all), then the condition of the patients will progressively worsen, and thrombocytopenia will appear (the phenomena of hemorrhagic diathesis make themselves felt) and severe anemia. Due to the fact that the size of the liver and spleen is growing rapidly, the volume of the abdomen noticeably increases, the condition of the diaphragm becomes high, the abdominal organs are compressed, and, as a consequence of these factors, the respiratory excursion of the lungs begins to decrease. Moreover, the position of the heart changes.
When chronic myeloid leukemia develops to this level, dizziness, shortness of breath, palpitations and headache appear against the background of pronounced anemia.
Monocyte crisis in myeloid leukemia
Regarding the topic of monocytic crisis, it should be noted that this is a rather rare phenomenon, during which young, atypical and mature monocytes appear and grow in the bone marrow and blood. Due to the fact that the bone marrow barriers are broken, at the terminal stage of the disease fragments of megakaryocyte nuclei appear in the blood. One of the most important elements of the terminal stage during a monocytic crisis is the inhibition of normal hematopoiesis (regardless of the morphological picture). The disease process is aggravated due to the development of thrombocytopenia, anemia and granulocytopenia.
In some patients, rapid enlargement of the spleen may be observed.
Diagnostics
The fact of progression of a disease such as chronic myeloid leukemia, the prognosis of which can be quite bleak, is determined through a whole complex of clinical data and specific changes in the process of hematopoiesis. In this case, histological studies, histograms and myelograms must be taken into account. If the clinical and hematological picture does not look clear enough and there is not enough data to confidently make a diagnosis, then doctors focus on detecting the Ph chromosome in monocytes, megakaryocytes, erythrocytes and granulocytes of the bone marrow.
In some cases, it is necessary to differentiate chronic myeloid leukemia. Diagnosis, which can be defined as differential, is aimed at identifying the typical picture of the disease with hyperleukocytosis and splenomegaly. If the option is atypical, then a histological examination of the spleen punctate is performed, as well as a myelogram study.
Certain difficulties can be observed when patients are admitted to the hospital in a state of blast crisis, the symptoms of which are very similar to myeloid leukemia. In such a situation, data from a thoroughly collected anamnesis, cytochemical and cytogenetic studies significantly help. Often chronic myeloid leukemia must be differentiated from osteomyelofibrosis, in which intense myeloid metaplasia can be observed in the lymph nodes, spleen, liver, as well as significant splenomegaly.
There are situations, and they are not uncommon, when a blood test helps to identify chronic myeloid leukemia in patients who have undergone a routine examination (in the absence of complaints and asymptomatic disease).
Diffuse myelosclerosis can be excluded by x-ray examination of bones, which reveals multiple areas of sclerosis in flat bones. Another disease that, although rare, still has to be differentiated from myeloid leukemia, is hemorrhagic thrombocythemia. It can be characterized by leukocytosis with a shift to the left and enlargement of the spleen.
Laboratory tests for the diagnosis of myeloid leukemia
In order to accurately determine the patient’s condition if chronic myeloid leukemia is suspected, a blood test can be performed in several directions:
Blood chemistry. It is used to identify disorders in the liver and kidneys that are a consequence of the use of certain cytostatic agents or were provoked by the spread of leukemia cells.
- Clinical blood test (complete). Necessary for measuring the level of various cells: platelets, leukocytes and red blood cells. In most patients who have had to deal with a disease such as chronic myeloid leukemia, the analysis reveals a large number of immature white cells. Sometimes a low platelet or red blood cell count may occur. Such results are not a basis for determining leukemia without an additional test that is aimed at examining the bone marrow.
Examination of bone marrow and blood samples under a microscope by a pathologist. In this case, the shape and size of the cells are studied. Immature cells are identified as blasts or myeloblasts. The number of hematopoietic cells in the bone marrow is also counted. The term “cellularity” is applicable to this process. In those with chronic myelogenous leukemia, the bone marrow tends to be hypercellular (large concentrations of hematopoietic cells and a high content of malignant cells).
Treatment
For a disease such as chronic myeloid leukemia, treatment is determined depending on the stage of development of tumor cells. If we are talking about mild clinical and hematological manifestations in the chronic stage of the disease, then nutritious nutrition enriched with vitamins, regular follow-up and restorative therapy should be considered as relevant therapeutic measures. Interferon can have a beneficial effect on the course of the disease.
If leukocytosis develops, doctors prescribe Myelosan (2-4 mg/day). If you have to deal with higher leukocytosis, then the dose of Myelosan can rise to 6 or even 8 mg/day. You should expect the manifestation of a cytopenic effect no earlier than 10 days after the first dose of the drug. A decrease in the size of the spleen and a cytopenic effect occurs on average during the 3-6th week of treatment, if the total dose of the drug was from 200 to 300 mg. Further therapy involves taking 2-4 mg of Myelosan once a week, which at this stage has a supporting effect. If the first signs of exacerbation make themselves known, myelosanotherapy is performed.
It is possible to use a technique such as radiation therapy, but only when splenomegaly is identified as the main clinical symptom. For the treatment of patients whose disease is in a progressive stage, poly- and monochemotherapy is relevant. If significant leukocytosis is recorded, if the effect of Myelosan is not sufficiently effective, Myelobromol (125-250 mg per day) is prescribed. At the same time, strict monitoring of peripheral blood parameters is carried out.
If significant splenomegaly develops, Dopan is prescribed (single dose 6-10 g/day). Patients take the drug once for 4-10 days. The intervals between doses are determined depending on the degree and rate of decrease in the number of leukocytes, as well as the size of the spleen. As soon as the decrease in leukocytes reaches an acceptable level, the use of Dopan is stopped.
If a patient develops resistance to Dopan, Myelosan, radiation therapy and Myelobromol, Hexaphosphamide is prescribed for treatment. In order to effectively influence the course of the disease in the progressive stage, the CVAMP and AVAMP programs are used.
If resistance to cytostatic therapy develops in a disease such as chronic myeloid leukemia, treatment in the progression stage will be focused on the use of leukocytopheresis in combination with a specific polychemotherapy regimen. As an urgent indication for leukocytopheresis, clinical signs of stasis in the vessels of the brain (a feeling of heaviness in the head, decreased hearing, headaches), which are caused by hyperthrombocytosis and hyperleukocytosis, can be identified.
If a blast crisis is detected, various chemotherapy programs used for leukemia can be considered relevant. Indications for transfusions of red blood cells, platelet concentrate and antibacterial therapy are infectious complications, the development of anemia and thrombocytopenic hemorrhage.
Regarding the chronic stage of the disease, it is worth noting that at this stage of development of myeloid leukemia, bone marrow transplantation is quite effective. This technique is capable of ensuring the development of clinical and hematological remission in 70% of cases.
An urgent indication for splenectomy in chronic myeloid leukemia is the threat of rupture or rupture of the spleen. Relative indications include severe abdominal discomfort.
Radiation therapy is indicated for those patients in whom extramedullary tumor formations that pose a threat to life have been identified.
Chronic myeloid leukemia: reviews
According to patients, such a diagnosis is too serious to ignore. By studying the testimonies of various patients, the real possibility of defeating the disease becomes obvious. To do this, you need to undergo timely diagnosis and subsequent treatment. Only with the participation of highly qualified specialists is there a chance to defeat chronic myeloid leukemia with minimal losses to health.
Clinical blood test for chronic myeloid leukemia. In the peripheral blood at the time of diagnosis, leukocytosis is detected, usually more than 50 10 9 / l (a lower level of leukocytes is possible - 15-20 109 / l) with a shift to the left due to band neutrophils, metamyelocytes, myelocytes, and rarely promyelocytes.
May be detected single blast cells(prognostically unfavorable sign). An eosinophilic-basophilic association is characteristic - an increase in the number of eosinophils and basophils, often morphologically abnormal. In 30% of cases, mild normochromic normocytic anemia is determined, in 30% of patients thrombocytosis is detected; less often - thrombocytopenia (unfavorable sign).
Myelogram with. When examining a myelogram (which is not always necessary to make a diagnosis), hypercellular bone marrow and hyperplasia of the neutrophilic lineage are revealed (the leukoerythroblastic ratio reaches 10-20:1 or more). Granulocytes in chronic myeloid leukemia have almost normal phagocytic and bactericidal activity.
Number of cells basophilic and eosinophilic series enlarged, abnormal forms are often encountered; Megakaryocytosis is possible.
Histological examination of bone marrow in chronic myeloid leukemia. When examining the bone marrow using trepanobiopsy, its hypercellularity and pronounced myeloid hyperplasia are revealed (leuko-erythroblastic ratio more than 10:1); the number of red blood cell precursors is reduced. Megakaryocytosis is observed in 40-50%, morphological atypia of cells is possible. With progression (acceleration phase), reticulin fibrosis often develops, and less commonly, collagen fibrosis of the bone marrow.
Cytogenetic and molecular genetic research in chronic myeloid leukemia. A cytogenetic study reveals a Ph chromosome in 95-97% of patients. In the absence of a Ph chromosome, fluorescent in situ hybridization (FISH) can detect 1 cell with a BCR-ABL translocation per 200-500 normal cells. The method is convenient for monitoring minimal residual disease; it is performed on peripheral blood samples, cytological and morphological preparations of blood and bone marrow, and sections of histological preparations.
PCR is also used to diagnose and monitor the disease, which allows one to identify one pathological cell among 10 4 -10 6 normal ones.
If both results are negative methods(cytogenetic and molecular genetic) one of the variants of MDS/MPD is diagnosed.
With molecular genetic research In patients in the acceleration phase and blast crisis, damage to a number of genes (TP53, RBI, MYC, RAS, pl6, AML1, EVI1) is detected, but their role in the transformation of the disease has not yet been established.
Cytochemical studies in chronic myeloid leukemia. A characteristic cytochemical sign of the advanced phase of chronic myeloid leukemia is a sharp decrease in the level of neutrophil alkaline phosphatase - up to 2-4 units. (norm - 8-80 units). Normal or elevated values do not exclude the diagnosis of chronic myeloid leukemia.
Biochemical studies in chronic myeloid leukemia. Characterized by an increase in the level of serum vitamin B12 and vitamin B12-binding capacity of blood serum due to increased production of transcobalamin by granulocytes. Increased cell destruction leads to hyperuricemia, especially with cytotoxic therapy. An increase in the iron-binding capacity of blood serum, histamine levels, and a decrease in leucine aminopeptidase may also be detected.
Diagnosis of chronic myeloid leukemia diagnosed on the basis of clinical and laboratory data (splenomegaly, leukocytosis with a shift in the leukocyte formula to the left and the presence of intermediate forms of neutrophils, eosinophilic-basophilic association, enhanced myelopoiesis in the bone marrow, low level of neutrophil alkaline phosphatase) and is confirmed by the detection of the Ph chromosome, t(9 ;22)(q34;qll.2) or the BCR-ABL gene (by cytogenetic or molecular genetic methods).
Highlight 3 stages of chronic myeloid leukemia: chronic, acceleration phase and blast crisis.
Criteria for determining the stage of chronic myeloid leukemia (WHO)
Chronic phase of chronic myeloid leukemia: there are no signs of other phases of the disease; no symptoms (after treatment).
Acceleration phase (in the presence of one or more signs) of chronic myeloid leukemia:
1) 10-19% blasts in the blood or bone marrow;
2) the number of basophils in peripheral blood is at least 20%;
3) persistent thrombocytopenia (less than 100 10 9 /l), not associated with treatment, or persistent thrombocytosis greater than 1000 10 9 /l, resistant to therapy;
4) increasing splenomegaly and leukocytosis, resistant to therapy (doubling the number of leukocytes in less than 5 days);
5) new chromosomal changes (appearance of a new clone).
Along with one of the above signs of the acceleration phase, proliferation of megakaryocytes associated with reticulin or collagen fibrosis or severe dysplasia of the granulocytic lineage is usually detected.
Blast crisis of chronic myeloid leukemia:
1) at least 20% blasts in the blood or bone marrow;
2) extramedullary proliferation of government cells;
3) a large number of aggregates of blast cells in the trephine biopsy specimen.
The main laboratory sign of the acceleration phase and blast crisis is a progressive increase in promyelocytes and blasts in the peripheral blood and bone marrow. Cytochemical studies in the blast crisis phase reveal a myeloid variant in 70% of patients and a lymphoid variant in 30%, which have similar features to AML and ALL, respectively:
a) the average age of patients with lymphoid crisis is less than that of patients with myeloid crisis;
b) neuroleukemia develops more often in patients with lymphoid crisis;
c) the immediate results of treatment in the lymphoid version of the crisis are significantly better.
Chronic myeloid leukemia is an oncological process that originates in immature cells of hematopoietic tissue located in the spleen parenchyma and bone marrow. This disease is dangerous to human life, because its development is accompanied by a pathological change in the blood, leading to early death. If a patient has chronic myeloid leukemia, emergency medical care is required.
Oncological damage to myeloid hematopoietic cells, the precursors of granular leukocytes, which is chronic, in most cases (95 out of 100) is associated with the appearance of an abnormal chromosome in them, which, according to the place of discovery, was called the Philadelphia chromosome.
The occurrence of this type of mutation occurs as follows:
- due to the influence of certain negative factors on the human body, a fusion of the abl genes from the 9th chromosome and bcr from the 22nd occurs;
- a pathological compound provokes the formation of an abnormal ABL-BCR protein, which activates the process of malignancy of blood cells;
- the blast cell, the future myeloid granular leukocyte, mutated due to a chromosomal disorder, stops in its development and begins to actively divide, forming a tumor structure in the bone marrow;
- clones of abnormal blood cells enter the bloodstream, where they also actively grow, displacing healthy platelets, leukocytes and red blood cells, thereby completely disrupting the functioning of the circulatory system.
The occurrence of such a violation in the DNA of leukocytes and an uncontrolled increase in abnormal cells in the blood leads to the development of cancer in the circulatory system. But it is almost never possible to identify chronic myeloid leukemia in the incipient phase, since this pathological condition is not accompanied for a long time by specific symptoms that can cause anxiety in a person.
Chronic myeloid leukemia in children
An oncological disease of this type is not typical for young patients; the diagnosis rate is only 1-5% of clinical cases of all childhood leukemia.
This pathological condition can occur in a small child in one of two types:
- Juvenile (related to adolescence) chronic myeloid leukemia. This type of disease is considered “adult” and predominates in children after 5 years of age. A characteristic feature of this type of disease is the presence of the Philadelphia chromosome in the structure of leukocytes.
- Infantile (underdeveloped, childhood) myeloid leukemia. This type of disease mainly affects children under two years of age and differs from the juvenile form in the absence of an abnormal chromosome in the blast cells. Another characteristic feature of this type of disease is a pronounced decrease in the number of leukocytes in the blood in sick children already at an early stage of the development of the pathological condition, which leads to frequent bleeding, which is very difficult to stop.
Worth knowing! The younger the child, the more acute the disease. Most often, the childhood form of myeloid leukemia is incurable - the baby’s death occurs very quickly due to the early development of thrombocytopenia, leading to extensive internal bleeding, which is often impossible to stop.
Classification of chronic myeloid leukemia
In clinical practice, chronic myeloid leukemia is usually divided into stages depending on how mature the blood cells that make up the tumor structures are.
The development of chronic myeloid leukemia goes through 3 phases, each of which is characterized by certain clinical signs and morphological changes in the blood:
- The chronic phase or the onset of a pathological process. Chronic myeloid leukemia begins to develop gradually. First of all, myeloid proliferation occurs (proliferation of bone marrow tissue due to activation of blast cell division), which leads to the appearance of specific changes in the blood. There are no general clinical signs at this stage, so chronic myeloid leukemia at the beginning of its development is usually an incidental finding.
- Acceleration phase, or transition. At this stage, clinical symptoms are mild and the patient’s condition can be considered stable. Only histological signs undergo changes - the quantitative composition of leukocytes and myelocytes begins to increase.
- Terminal, final phase. The final stage of the disease is characterized by the appearance of pronounced clinical signs that are difficult to tolerate by patients. Their appearance indicates the onset of a blast crisis. One of the features of the disease, which is always accompanied by the final phase, is an infarction of the spleen and its obvious increase due to the accumulation of a large number of blast cells in the hematopoietic organ. In more than half of patients at this phase of the disease, fibrosis (tissue enlargement) of the bone marrow is detected.
Worth knowing! It is usually possible to detect chronic myeloid leukemia of the bone marrow, spleen and blood in the last phase of the disease, which is due to the absence of specific symptoms at stages 1 and 2. Such insidiousness of the disease leads to frequent deaths, but its slow development, which can last for many years, brightens up this picture, since in many patients it is possible to identify the pathological condition in the early phase, when diagnosing another disease.
Reasons that provoke the development of blood pathologies
Chronic myeloid leukemia is the first and only cancer whose cause has been reliably established. The main prerequisite that provokes the onset of the disease is the appearance of an abnormal chromosome in the blast cells of the hematopoietic organs. The disease that arises as a result of such a genetic mutation develops very slowly, and a person can live into old age without learning about the presence of oncological pathology in his blood. But the development of chronic myeloid leukemia can also be rapid.
The disease can quickly, within a few months, reach its final phase if there are certain risk factors in a person’s life, the main ones of which are considered to be:
- living in areas with increased background radiation or areas in close proximity to nuclear power plants;
- long-term treatment with cytostatics or uncontrolled use of antibacterial drugs that have increased toxicity;
- regular, long-term exposure to toxic and chemical substances on the human body;
- a person's history of Klinefelter or Down syndrome.
If at least one of these risk factors is present in a person’s life, he needs to be more attentive to his well-being and, if minimal health problems appear, consult a specialist for advice. Also, annual preventive diagnostics are recommended for people at risk. Timely detection of pathological changes in blood composition allows the developing chronic form of myeloid leukemia to be completely cured.
Symptoms of oncopathology of the hematopoietic organs
Signs of the disease are absent for a long time; the first specific symptoms of chronic myeloid leukemia, causing a person to become alarmed and visit a doctor, usually appear in the terminal stage of the disease, when it is impossible to cure it. The initial phase of the disease is characterized by vague, mild symptoms. But knowing them, you can suspect the development of a pathological condition and, by contacting a hemato-oncologist in a timely manner, diagnose chronic myeloid leukemia in an early phase that responds well to therapy.
The main signs that should raise alarm include:
- swollen lymph nodes;
- anemia, characterized by pale skin;
- constant feeling of malaise and fatigue;
- unreasonable loss of appetite and weight loss;
- the appearance of bruises and bruises on the skin;
- frequent and prolonged external or internal bleeding;
- feeling of fullness on the left side of the abdominal cavity due to an increase in the size of the spleen.
These symptoms are typical for many diseases, but their appearance cannot be ignored, because they may indirectly indicate a developing blood cancer. Often it is thanks to the patient’s complaints about the presence of these signs that a dangerous disease can be detected in a timely manner.
Diagnostics includes laboratory and instrumental methods to confirm or refute the development of the disease
If chronic myeloid leukemia is suspected, the doctor first collects an anamnesis and conducts a physical examination to detect changes in the skin, enlargement of the lymph nodes, spleen and liver, which indirectly indicate the presence of a pathological process of malignancy in the human hematopoietic system. If these signs are present, patients with suspected development of chronic myeloid leukemia are referred to undergo special diagnostic tests, the main of which is laboratory diagnostics, including:
- general and biochemical, with the help of which the quantitative and qualitative composition of biological fluid is recorded;
- histological examination of biopsy material taken through fine-needle puncture from the bone marrow.
To clarify the nature of the course of chronic myeloid leukemia, all patients are prescribed additional. The most informative tests for this disease are radiography, ultrasound examination of the abdominal cavity, CT and MRI. Using these techniques, specialists not only clarify the nature of the oncological process, but also identify the presence of secondary malignant foci.
Informative video
Types of therapy for chronic myeloid leukemia: medication, surgery, radiation
All therapeutic measures used to stop the oncological process that has affected the hematopoietic organs are prescribed by a hemato-oncologist based on the phase of development of the disease, general signs characterizing its course and the severity of the clinical picture accompanying chronic myeloid leukemia.
Therapeutic measures are prescribed individually to each patient, depending on the stage of the disease:
- In the initial, chronic phase, no special treatment is required. To maintain a stable condition in patients, they are prescribed general restorative therapy, which consists of correcting nutrition, reducing physical activity and observing a work-rest regime.
- The activation phase of chronic myeloid leukemia requires expansion of therapeutic measures. Patients are required to undergo courses of biological therapy with Interferon and chemistry with Chloroethylaminouracil, Hexaphosphamide or Mitobronitol. According to indications, it can be prescribed.
- When a blast crisis occurs, treatment becomes useless. At this final phase of the disease, patients receive exclusively symptomatic therapy to alleviate the painful symptoms of the disease and maintain quality of life until the last days.
Prognosis for recovery
It is possible to stop developing chronic myeloid leukemia only at the initial stage of the pathological process, provided that the treatment is carried out correctly. But this happens very rarely, since timely detection of the disease presents serious difficulties. Most patients die in the transition or terminal phase of chronic myeloid leukemia. From diagnosis of the disease to death at these stages of the disease, it takes about two years. Of particular danger is the onset of blast crisis - during this phase, cancer patients live no longer than six months. The most unfavorable is the presence of an abnormal Philadelphia chromosome in the blood genes.
Prevention of myeloid leukemia
There are currently no specific preventive measures to prevent chronic myeloid leukemia. The only thing hemato-oncologists advise people who are at risk for developing an oncological process in the hematopoietic organs is regular screening tests.
- with the inclusion in the daily menu of dishes enriched with vitamin and mineral complexes;
- complete cessation of addictions (smoking, alcohol abuse, evening overeating), or reducing them to a minimum;
- maintaining an active, healthy lifestyle with regular participation in feasible sports;
- Reducing exposure to ultraviolet radiation: avoiding exposure to direct sunlight.
Informative video
Treatment for chronic myeloid leukemia begins after diagnosis and is usually carried out on an outpatient basis.
In the absence of symptoms of chronic myeloid leukemia against the background of stable leukocytosis not exceeding 9/l, hydroxyurea or busulfan is used until the leukocyte count in the blood reaches 20*109/l.
As chronic myeloid leukemia progresses, hydroxyurea (Hydra, Litalir) and α-IFN are indicated. If there is significant splenomegaly, the spleen is irradiated.
For severe symptoms of chronic myeloid leukemia, combinations of drugs used for acute leukemia are used: vincristine and prednisolone, cytarabine (Cytosar) and daunorubicin (rubomycin hydrochloride). At the onset of end-stage disease, mitobronitol (myelobromol) is sometimes effective.
Currently, a new drug, the mutant tyrosine kinase (p210) blocker Gleevec (STI-571), has been proposed for the treatment of chronic myeloid leukemia. During blast crisis of CML and Ph-positive ALL, the dose is increased. The use of the drug leads to complete remission of the disease without eradication of the tumor clone.
Transplantation of blood stem cells or red bone marrow, performed in patients under 50 years of age in stage I of the disease, leads to recovery in 70% of cases.
With chemotherapy, the average life expectancy is 34 years. Death in chronic myeloid leukemia usually occurs during blast crisis from infectious complications and hemorrhagic syndrome. Life expectancy from the moment signs of blast crisis appear rarely exceeds 12 months. The prognosis is influenced by the presence of the Philadelphia chromosome (prognostically unfavorable) and the sensitivity of the disease to therapy (favorable). The use of α-IFN significantly increases the effect of treatment.
Chronic myeloid leukemia: blood picture and life prognosis for patients
Tumor pathologies often affect the circulatory system. One of the most dangerous pathological conditions is chronic myelogenous leukemia, a cancerous blood disease characterized by random proliferation and growth of blood cells. This pathology is also called chronic myeloid leukemia.
The disease rarely affects children and adolescents, more often found in older patients, more often than males.
What is chronic myeloid leukemia?
Essentially, myeloid leukemia is a tumor formed from early myeloid cells. The pathology is clonal in nature and among all hemoblastoses it accounts for about 8.9% of cases.
Chronic myeloid leukemia is characterized by an increase in the blood composition of a specific type of leukocytes called granulocytes. They are formed in the red bone marrow and enter the blood in large quantities in an immature form. At the same time, the number of normal leukocyte cells decreases.
Causes
The etiological factors of chronic myeloid leukemia are still the subject of study and raise many questions among scientists.
It has been reliably revealed that the following factors affect the development of chronic myeloid leukemia:
- Radioactive exposure. One of the proofs of such a theory is the fact that among the Japanese who were in the zone affected by the atomic bomb (the case of Nagasaki and Hiroshima), cases of the development of a chronic form of myeloid leukemia have become more frequent;
- The influence of viruses, electromagnetic rays and substances of chemical origin. This theory is controversial and has not yet received final recognition;
- Hereditary factor. Studies have shown that in individuals with chromosomal abnormalities, the likelihood of developing myeloid leukemia increases. Usually these are patients with Down syndrome or Klinefelter syndrome, etc.;
- Taking certain medications, such as cytostatics, used in the treatment of tumors in conjunction with radiation. In addition, alkenes, alcohols and aldehydes can be hazardous to health in this regard. Nicotine addiction, which aggravates the condition of patients, has a very negative impact on the well-being of patients with myeloid leukemia.
Structural disturbances in red bone marrow cell chromosomes lead to the birth of new DNA with an abnormal structure. As a result, clones of abnormal cells begin to be produced, which gradually displace normal ones to such an extent that their percentage in the red bone marrow becomes prevalent.
As a result, abnormal cells multiply uncontrollably, similar to cancer cells. Moreover, their natural death does not occur according to generally accepted traditional mechanisms.
The following video will explain the concept of chronic myeloid leukemia and its causes:
Once in the general bloodstream, these cells, which have not matured into full-fledged leukocytes, do not cope with their main task, which causes a lack of immune protection and resistance to inflammation and allergic agents with all the ensuing consequences.
The development of chronic myeloid leukemia occurs in three successive phases.
- The phase is chronic. This stage lasts about 3.5-4 years. Usually it is with this that most patients end up seeing a specialist. The chronic phase is characterized by constancy, because patients have the minimum possible set of symptom-complex manifestations. They can be so insignificant that patients sometimes do not attach any importance to them. A similar stage can be detected by a random blood test.
- Acceleration phase. It is characterized by activation of pathological processes and a rapid increase in immature leukocytes in the blood. The duration of the acceleration period is a year and a half. If the treatment process is selected adequately and started on time, then the likelihood of the pathological process returning to the chronic phase increases.
- Blast crisis or terminal phase. This is the acute stage, it lasts no more than six months and ends in death. It is characterized by almost complete replacement of red bone marrow cells by abnormal malignant clones.
In general, the pathology is characterized by a leukemic development scenario.
Symptoms
The clinical picture of myeloid leukemia varies according to the phase of the pathology. But general symptoms can also be identified.
Chronic stage
The following manifestations are typical for this stage of chronic myeloid leukemia:
- Mild symptoms characteristic of chronic fatigue. General health worsens, concerns about impotence, weight loss;
- Due to the increase in the volume of the spleen, the patient notes rapid saturation when eating, and pain often occurs in the left abdominal region;
- In exceptional cases, rare symptoms occur associated with thrombus formation or blood thinning, headaches, memory and attention disorders, visual disturbances, shortness of breath, and myocardial infarction.
- In this phase, men may develop an erection that is too long and causes pain or priapic syndrome.
Accelerative
The accelerated stage is characterized by a sharp increase in the severity of pathological symptoms. Anemia progresses rapidly, and the therapeutic effect of cytostatic drugs decreases noticeably.
Laboratory blood diagnostics show a rapid increase in leukocyte cells.
Terminal
The blast crisis phase of chronic myeloid leukemia is characterized by a general deterioration of the clinical picture:
- The patient has pronounced febrile symptoms, but without an infectious etiology. The temperature can rise to 39°C, causing a sensation of severe trembling;
- Hemorrhagic symptoms are intensely manifested, caused by bleeding through the skin, intestinal membranes, mucous tissues, etc.;
- Severe weakness bordering on exhaustion;
- The spleen reaches incredible sizes and is easily palpated, which is accompanied by heaviness and pain in the abdomen on the left.
The terminal stage is usually fatal.
Diagnostic methods
A hematologist is in charge of diagnosing this form of leukemia. It is he who conducts the examination and prescribes laboratory blood tests and ultrasound diagnostics of the abdominal area. Additionally, a bone marrow puncture or biopsy, biochemistry and cytochemical studies, and cytogenetic analysis are performed.
Blood picture
For chronic myeloid leukemia, the following blood picture is typical:
- At the chronic stage, the share of myeloblasts in the bone marrow fluid or blood accounts for about 10-19%, and basophils - more than 20%;
- At the terminal stage, lymphoblasts and myeloblasts exceed the 20% threshold. When performing a biopsy examination of bone marrow fluid, large accumulations of blasts are detected.
Treatment
The therapeutic process of treatment of chronic myeloid leukemia consists of the following areas:
Chemotherapy treatment involves the use of traditional drugs such as Myelosan, Cytosar, Hydroxyurea, etc. The newest drugs of the latest generation are also used - Sprycel or Gleevec. The use of medications based on hydroxyurea, Interferon-α, etc. is also indicated.
After the transplant, the patient has no immune protection, so he is in the hospital until the donor cells take root. Gradually, bone marrow activity returns to normal and the patient recovers.
If chemotherapy is not effective, radiation is used. This procedure is based on the use of gamma rays, which are applied to the area where the spleen is located. The goal of such treatment is to stop the growth or destroy abnormal cells.
In exceptional situations, removal of the spleen is indicated. Such intervention is carried out mainly during the blast crisis phase. As a result, the overall course of the pathology is significantly improved, and the effectiveness of drug treatment increases.
When the leukocyte level reaches excessively high levels, leukopheresis is performed. This procedure is almost identical to plasmapheresis blood purification. Leukapheresis is often included in complex drug therapy.
Life expectancy forecast
The majority of patients die in the accelerated and terminal stages of the pathological process. About 7-10% die after being diagnosed with myeloid leukemia in the first 24 months. And after a blast crisis, survival can last about 4-6 months.
If remission can be achieved, the patient can survive after the terminal stage for about a year.
Detailed video about the diagnosis and treatment of chronic myeloid leukemia:
Chronic myeloid leukemia
Oncological diseases often affect the circulatory system. One of the dangerous conditions is chronic myeloid leukemia, which is a blood cancer.
The disease is accompanied by chaotic proliferation of blood cells. More often the disease is diagnosed in older men. In children and women, the disease occurs much less frequently, however, the possibility of the disease cannot be completely excluded.
CML is a tumor composed of myeloid cells. The nature of the disease is clonal; among other hemoblastoses, the disease accounts for up to 9% of cases. The course of the disease may not manifest itself with special symptoms at first. To diagnose this condition, you need to take a blood smear and bone marrow sample for analysis. Myeloid leukemia is characterized by an increased number of granulocytes (a type of white blood cell) in the blood. These leukocytes are formed in the bone marrow red matter and enter the bloodstream in an immature form. At the same time, the number of normal white blood cells decreases. The doctor can see this picture in the results of blood tests.
Causes of myeloid leukemia
Scientists have not yet fully established the etiology of the disease, but it has been established that chronic myeloid leukemia can be provoked by the following factors:
- exposure to radiation. The relationship between radiation and oncology can be proven by examples of the Japanese who were in Hiroshima and Nagasaki during the explosion of the atomic bomb. Subsequently, many of them were diagnosed with the development of chronic myeloid leukemia;
- influence of chemicals, electromagnetic radiation, viruses. The theory is controversial in the scientific community and has not yet received scientific recognition;
- heredity. According to research, the risk of developing myeloid leukemia is greater in people with chromosomal disorders (Down syndrome, Klinefelter syndrome, etc.);
- treatment with certain medications that are intended for the treatment of tumors against the background of radiation. Aldehydes, alkenes, alcohols, and tobacco smoking also increase the risk of getting sick. This is another reason to think that a healthy lifestyle is the only right choice for a sane person.
Due to the fact that the structure of the red cell chromosomes in the bone marrow is disrupted, new DNA appears, the structure of which is abnormal. Next, the abnormal cells are cloned, gradually displacing normal cells, until the situation when the number of abnormal clones begins to greatly predominate. As a result, abnormal cells multiply and grow in number uncontrollably, just like cancer cells. They do not obey the traditional mechanism of natural death.
When they enter the bloodstream, abnormal white blood cells do not perform their main task, leaving the body without protection. Therefore, a person who develops chronic myeloid leukemia becomes susceptible to allergies, inflammation, etc.
Phases of myeloid leukemia
Chronic myeloid leukemia develops gradually, sequentially passing through 3 important phases, which can be found out below.
The chronic phase lasts about 4 years. It is at this time that the patient usually consults a doctor. In the chronic stage, the disease is characterized by stability, so minimal symptoms may practically not bother a person. It happens that the disease is discovered by chance during the next blood test.
The acceleration phase lasts about one and a half years. At this time, the pathological process is activated, the number of immature leukocytes in the bloodstream increases. With the right choice of therapy and timely response, the disease can be returned to the chronic phase.
The terminal phase (blast crisis) lasts less than six months and ends fatally. The stage is characterized by exacerbation of symptoms. At this time, red bone marrow cells are completely replaced by abnormal clones of a malignant nature.
Symptoms of myeloid leukemia
Depending on the stage of chronic myeloid leukemia at the moment, the symptoms will differ. However, it is possible to identify common features characteristic of the disease at different stages. Patients show obvious lethargy, weight loss, and loss of appetite. As the disease progresses, the spleen and liver enlarge and the skin becomes pale. Patients experience bone pain and excessive sweating at night.
As for the symptoms of each phase, for the chronic stage the characteristic signs will be: deterioration in health, loss of strength, weight loss. While eating, patients quickly feel full, and pain often occurs in the left abdominal area. Rarely in the chronic phase, patients complain of shortness of breath, headaches and visual disturbances. Men may experience prolonged, painful erections.
For the accelerated form, the characteristic signs will be: progressive anemia, the severity of pathological symptoms, the results of laboratory tests will show an increase in the number of leukocyte cells.
The terminal stage is characterized by worsening of the disease picture. A person often gets feverish for no obvious reason. The temperature can rise to 39 degrees, the person feels trembling. Bleeding through mucous membranes, skin, and intestines is possible. The person feels severe weakness and exhaustion. The spleen enlarges to its maximum, giving pain in the left side of the abdomen and a feeling of heaviness. As mentioned above, the terminal stage is followed by death. Therefore, it is better to start treatment as early as possible.
A hematologist can diagnose myeloid leukemia in a person. He conducts a visual examination, listens to complaints and sends the patient for an ultrasound of the abdomen and a blood test. Additionally, biochemistry, biopsy, bone marrow puncture, and cytochemical studies are performed. The blood picture in the test results will indicate the presence of the disease if:
- the proportion of myeloblasts in the blood or bone marrow fluid is up to 19%, basophils - over 20% (chronic phase);
- the proportion of myeloblasts and lymphoblasts exceeds 20%, bone marrow biopsy shows large accumulations of blasts (terminal phase).
Treatment of myeloid leukemia
The doctor determines exactly how to treat the disease, taking into account the stage of the disease, the presence of contraindications, concomitant diseases, and age. If the disease proceeds without any special symptoms, then for the treatment of such a condition as chronic myeloid leukemia, treatment is prescribed in the form of general strengthening agents, nutritional correction, taking vitamin complexes, and regular observation in a dispensary. According to scientists, a-interferon has a beneficial effect on the condition of patients.
As for the prescription of drugs, if the test results for leukocytes are 30-50*109/l, the patient is prescribed myelosan in an amount of 2-4 mg/day. When the levels increase to *109/l, the dose of the drug increases to 6 mg/day. If leukocytosis exceeds the specified values, the daily dose of myelosan is increased to 8 mg. The effect will be noticeable approximately 10 days from the start of therapy. The hemogram will normalize against the background of a decrease in the size of the spleen during approximately 3-6 weeks of therapy, when the total dose of the drug will be 250 mg. Next, the doctor prescribes maintenance treatment by taking myelosan once a week at a dosage of 2-4 mg. You can replace maintenance treatment with regular courses of the drug in case of exacerbation of the process, if the number of leukocytes increases to 20-25*109/l against the background of an enlarged spleen.
Radiation therapy (radiation) is prescribed as the primary treatment in some cases when splenomegaly is the main symptom. Irradiation is prescribed only if the level of leukocytes in tests is above 100*109/l. As soon as the indicator drops to 7-20*109/l, irradiation is stopped. After about a month, body support with melosan is prescribed.
During the treatment of the progressive phase of chronic myeloid leukemia, mono- and poly-type chemotherapy is prescribed. If tests show significant leukocytosis, and myelosan does not have an effect, myelobromol is prescribed pomg per day, monitoring peripheral blood parameters. After about 2-3 weeks, the hemogram returns to normal, after which maintenance therapy can begin by taking myelobromol pomg once every 7-10 days.
In case of severe splenomegaly, dopan is prescribed if other drugs and anti-leukemia drugs do not give the desired effect. In this case, dopan is taken 6-10 mg once every 4-10 days (as prescribed by a doctor). The interval between doses of the drugs will depend on the rate at which the number of leukocytes in the blood decreases and how the size of the spleen changes. As soon as the number of leukocytes decreases to 5-7*109/l, dopan can be discontinued. It is best to take the medication after dinner, and then take sleeping pills. This is due to the possibility of dyspeptic symptoms. For maintenance therapy, the doctor may prescribe dopam at a dosage of 6-10 mg every 2-4 weeks, monitoring the hemogram.
If doctors observe that the disease exhibits resistance to dopan, myelosan, myelobromol and radiation, then they prescribe hexaphosphamide to the patient. If the test results show the number of leukocytes reaches 100*109/l, then hexaphosphamide is prescribed 20 mg daily; if the level is 40-60*109/l, it is enough to take mg of the drug twice a week. As the number of abnormal leukocytes in the blood decreases, the doctor reduces the dosage of the drug, and as soon as the levels drop to 10-15 * 109/l, treatment with the drug is stopped. The course of treatment is usually calculated on the dose of drugs mg posterior. Positive results from treatment with the drug are usually observed after 1-2 weeks. If maintenance therapy is necessary, hexaphosphamide is prescribed pomg once every 5-15 days. The doctor prescribes the intervals individually, taking into account the dynamics of treatment and the patient’s health condition.
For the treatment of the progressive phase of chronic myeloid leukemia, drug programs ABAMP and CVAMP are prescribed. The ABAMP program consists of two 10-day courses with a 10-day break. The list of drugs includes: cytosar (30 mg/m2 on days 1 and 8 intramuscularly), methotrexate (12 mg/m2 on days 2, 5 and 9 intramuscularly), vincristine (1.5 mg/m2 on days 3 and 10 intravenously) , 6-mercaptopurine (60 mg/m2 every day), prednisolone (50-60 mg/day if thrombocytopenia is less than 100*109/l). If the number of leukocytes exceeds 40*109/l, hyperthrombocytosis persists, then prednisolone is not prescribed.
The ABAMP program is a whole course of drugs similar to the previous program, but instead of cytosar, cyclophosphamide pomg is prescribed intramuscularly every other day. Polychemotherapy is carried out 3-4 times during the year, and in the intervals between courses, myelosan is prescribed according to the general scheme and 6-mercaptopurine (100 mg every day for 10 days with a 10-day break).
In the treatment of chronic myeloid leukemia, including blast crises, hydroxyurea is prescribed. It has contraindications: leukopenia (white blood cell count below 3*109/l) and thrombocytopenia (platelet count in tests less than 100*109/l). Initially, the drug is prescribed at 1600 mg/m every day. If leukocytes in the blood become less than 20*10/l, then the drug is prescribed at 600 mg/m2, and if the number of leukocytes drops to 5*109/l, the drug is discontinued.
In case of resistance to cytostatics and progression of myeloid leukemia, doctors can prescribe leukocytapheresis in parallel with one of the above polychemotherapy regimens. Indications for leukocytapharesis are clinical manifestations of stasis in the vessels of the brain (decreased hearing and pain in the head, a feeling of “hot flashes”, heaviness in the head) against the background of hyperthrombocytosis and hyperleukocytosis.
In the blast crisis stage, chemotherapy is prescribed, which is effective for acute leukemia. For anemia and infectious complications, transfusion of red blood cells, platelet concentrate and antibacterial therapy are prescribed.
If a patient is diagnosed with extramedullary tumor formations (tonsils covering the larynx, etc.) that threaten his life, then radiation therapy is prescribed.
Bone marrow transplantation is used in cases of chronic myeloid leukemia in the chronic phase. Thanks to transplantation, remission occurs in approximately 70% of patients.
Splenectomy in the case of chronic myeloid leukemia is prescribed for splenic rupture and a condition that is fraught with rupture. Indications may be: severe discomfort in the abdomen, which is associated with the huge size of the spleen, as well as pain syndrome due to repeated perisplenitis, deep thrombocytopenia, hemolytic crisis, syndrome of the “wandering” spleen with the risk of twisting of the leg.
Prognosis for chronic myeloid leukemia
The disease is a life-threatening condition. Most patients say goodbye to life at the accelerated and terminal stages of the disease. Up to 10% of patients diagnosed with myeloid leukemia die within 2 years. After the blast crisis phase, life expectancy can be up to six months.
If it is possible to achieve remission during the terminal phase, the patient's life can last up to a year. However, at any stage of the disease you should not give up. It is likely that the statistics do not include all cases where the disease was extinguished and the life with it was extended by several years, perhaps by decades.
Chronic myeloid leukemia and life expectancy
Chronic myeloid leukemia is determined by the growth and division of blood cells, and this happens uncontrollably. Simply put, it is a malignant blood disease of a clonal nature, in which cancer cells are able to mature to mature forms. A synonym for chronic myeloid leukemia is chronic myeloid leukemia, popularly called “bleeding”.
The bone marrow produces blood cells; in myeloid leukemia, immature cells are formed in the blood, which doctors call blasts, so in some cases this disease is called chronic myeloid leukemia. Blasts gradually displace healthy blood cells and penetrate through the bloodstream into all organs of the human body.
The mechanism of development of the disease
A human cell contains 46 chromosomes. Each of them has sections that are located in a certain sequence - they are called genes. Each segment (gene) is responsible for the production of proteins (only one type) that the body needs for life.
Under the influence of provoking factors - radiation and other factors, including unknown ones, two chromosomes exchange their sections with each other. The result is an altered chromosome, which scientists call the Philadelphia chromosome (since it was first discovered there). It is known that this chromosome regulates the production of a certain protein, which causes mutation processes in the cell, that is, allows it to divide uncontrollably.
Atypical cells often appear in a healthy body, but the immune system quickly destroys them. But the Philadelphia chromosome gene gives it stability, and the body’s defenses cannot destroy it. As a result, after some time, the number of changed cells exceeds the number of healthy and unchanged ones, and chronic myeloid leukemia develops.
Reasons for the development of the disease
The etiology of CML has not yet been fully studied; scientists around the world are struggling with this issue; as soon as the cause of the disease is discovered, there will be a cure for this disease. All cells originate from stem cells, which are mainly localized in the bone marrow; after their maturation is completed, the cells begin their functions.
Leukocytes - protect against infection, red blood cells deliver oxygen and other substances to all cells, platelets - prevent bleeding by forming clots. As a rule, it is the leukocyte cell that begins to divide uncontrollably, however, not all cells mature, so a large number of mature and immature cells end up in the bloodstream.
Currently, only indirect reasons why the disease develops are known:
- Stem cells change their structure, this mutation gradually progresses, and as a result, blood cells become pathological. They are called “pathological clones”. Cytostatic drugs cannot eliminate them or stop their division.
- Harmful chemicals.
- Radiation. Sometimes patients who have received radiation therapy to treat other malignancies are diagnosed with chronic myeloid leukemia.
- Long-term exposure to the body of cytostatic drugs, which are also used to treat cancer. There is a whole list of drugs that can provoke chronic myeloid leukemia.
- Down syndrome.
- Pathological effects of aromatic carbohydrates.
- Viruses.
However, all these reasons cannot give a complete picture of the etiology of the disease, since they are only indirect; the true cause is not yet known to science.
Types of leukemia
Myeloid leukemia is distinguished by the nature of the course and the type of pathological cells. According to the course of the disease, acute and chronic forms are distinguished. Chronic myeloid leukemia is characterized by a slower development of pathology, and certain changes occur in the blood, which does not happen in the acute form.
Based on cellular composition, leukemia is divided into:
- promyelocintaric;
- myelomonocytic, which in turn is also divided into several subtypes;
- myelomonoblastic;
- basophilic;
- megakaryoblastic;
- erythroid leukemias.
As for the chronic form, it is divided into juvenile, myelocintic, myelomonocintic (CMML), neutrophilic and primary.
Chronic myelomonocytic leukemia differs from chronic myeloid leukemia in that the largest leukocytes (monocytes), which do not have granules, are cloned and enter the bloodstream while still immature.
Stages of chronic myeloid leukemia
Chronic myeloid leukemia occurs in three stages:
If at the initial stage of the disease the patient does not receive adequate treatment, then myeloid leukemia gradually passes through all three stages, however, with timely and correct treatment, the disease can be slowed down at the initial or advanced stage.
The chronic (initial) stage can be observed for a long time, while symptoms are practically absent and the presence of pathology can only be determined by taking a blood test. The patient may only feel some discomfort, which, as a rule, is not paid attention to. Sometimes after eating you may feel full, which is due to an enlarged spleen.
The acceleration phase (advanced stage) is the next stage of the disease. With its onset, clinical signs become more pronounced, which indicates that the leukemic process is developing. The patient experiences profuse sweating, loss of strength, fever, weight loss, and pain in the left side under the ribs. In addition, heart pain and arrhythmia may appear - this indicates that the process has transferred to the cardiovascular system.
The final stage of the disease is terminal (blast crisis). The patient's condition deteriorates sharply, the temperature continues to rise and no longer drops to normal levels. At this stage, the patient’s body no longer responds to drug treatment; infections often join the process, which, as a rule, become the cause of death.
Clinical picture
The chronic form of myeloid leukemia is diagnosed in 15% of all cases of the disease. When diagnosed with chronic myeloid leukemia, the symptoms are not expressed at first, the disease can continue asymptomatically for about 4-5 years, in some cases up to 10 years. The first striking symptom that a person can pay attention to is an increase in temperature for no apparent reason. An increase in temperature occurs due to an enlargement of the spleen and liver, which can cause some pain and discomfort in the right and left side.
The organs are painful on palpation. If basophils in the blood increase significantly, the patient may experience skin itching and a feeling of heat; if the terminal stage is close, joint pain may occur. In some cases, there is a risk of splenic infarction; if there is damage to the brain centers, then paralysis is possible. Lymph nodes are enlarged.
One of the forms of chronic myeloid leukemia is juvenile myelosis. It is diagnosed in preschool children. This disease does not have an acute form, and symptoms increase gradually:
- the child is not active;
- often suffers from infectious diseases;
- has poor appetite and does not gain weight well;
- development is inhibited;
- Nosebleeds are often observed.
Diagnosis of the disease
Most often, a blood test helps to suspect the disease; in addition, the doctor may be alerted to hepatomegaly and an enlarged spleen. A hematologist can refer the patient for an ultrasound and genetic testing.
The patient's blood is subjected to the following diagnostics:
A detailed blood test helps to track the dynamics of cellular composition. If the patient has the initial stage of the disease, then healthy, mature blood cells are assessed and the number of immature blood structures is determined. During the accelerated stage, the analysis shows an increase in immature blood cells and a sharp change in platelet levels. When blasts reach 20%, we can say that the final stage of the disease has arrived.
Biochemical analysis determines the level of uric acid and other indicators that are characteristic of chronic myeloid leukemia. Cytochemistry is performed to differentiate the chronic form of leukemia from other forms of the disease.
During a cytogenetic study, specialists identify atypical chromosomes in blood cells. This is necessary not only for a definitive diagnosis, but also for predicting the course of the disease.
Biopsy – needed to identify atypical cells; a specialist takes material from the femur for analysis. Ultrasound, CT and MRI give an idea of the size of the liver and spleen, which also helps to distinguish the chronic form of sapwood from leukemia of other forms.
Treatment of the disease
When diagnosed with chronic myeloid leukemia, treatment is determined according to the stage of the disease. If hematological and symptomatic manifestations are not pronounced, then experts recommend good nutrition, vitamin therapy, general strengthening measures, as well as regular examinations. In other words, tactics are chosen to monitor the disease and strengthen the body’s immune forces.
Some doctors talk about the positive dynamics of the course of the disease when using interferon. If the patient is bothered by nosebleeds (or other) or he begins to suffer from infectious diseases more often, then strengthening measures alone will not be enough, more aggressive treatment must be taken.
At later stages of the disease, cytostatics are used, which block the growth of all cells. These are essentially cellular poisons; of course, they suppress the growth of cancer cells, but they also cause severe adverse reactions in the body. This includes nausea, poor health, hair loss, and inflammatory processes in the intestines and stomach. Bone marrow transplants and blood transfusions are practiced. In some cases, bone marrow transplantation can completely cure the patient, however, for the success of this operation, a completely compatible bone marrow donor is necessary for the patient.
It is impossible to treat myeloid leukemia on your own or with the help of traditional medicine. Medicinal herbs only help strengthen the patient’s body and increase his immunity. In the final stage of the disease, drugs are prescribed that are used for acute leukemia.
Studies conducted at the end of the last century showed that Imatinib (Gleevec) can lead to hematological remission. This occurs due to the fact that the Philadelphia chromosome disappears in the blood, which is the cause of the development of chronic myeloid leukemia. To date, relatively little experience has been accumulated to allow us to discuss the advantages and disadvantages of this drug. But we can say with confidence that it is superior to previously known medications that were used to treat chronic myeloid leukemia.
In extreme cases, the patient’s spleen is removed; as a rule, such intervention is performed during blast crisis. After removal of the hematopoietic organ, the course of the disease improves, and the effectiveness of drug treatment also increases.
Provided that the level of leukocytes increases extremely high, patients undergo leukopheresis. In essence, this procedure is similar to plasma purification. Often this procedure is prescribed in combination with drug treatment.
Forecasts for life
The prognosis for the chronic course of the disease is unfavorable, since this disease is a life-threatening illness. Death most often occurs in the accelerative and final stages of the disease. The average life expectancy for patients is 2 years.
After a blast crisis, patients die after about six months, but if remission is achieved, then life expectancy increases by about a year. However, you should not give up, no matter what stage the disease occurs, there is always a chance to prolong life. Perhaps the statistics do not include isolated cases where remission lasted for years, besides, scientists do not stop conducting research, and perhaps very soon a new method of effective treatment of chronic myeloid leukemia will appear.