18.02.2017
Cancer often affects the circulatory system. One of the dangerous conditions is chronic myeloid leukemia, which is a blood cancer.
The disease is accompanied by a chaotic reproduction of blood cells. Most 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 ruled out.
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 be manifested by special symptoms at first. To diagnose such a condition, you need to take a blood smear, a bone marrow test for analysis. Myeloid leukemia is characterized by an increased number of granulocytes in the blood (a type of white blood cell). 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 leukocytes decreases. The doctor can see such a picture in the results of blood tests.
Causes of myeloid leukemia
Until the end, scientists have not yet 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 examples of the Japanese who were in Hiroshima and Nagasaki during the explosion of the atomic bomb can prove the relationship between radiation and oncology. Subsequently, many of them were diagnosed with the development of chronic myeloid leukemia;
- the influence of chemicals, electromagnetic radiation, viruses. The theory is controversial in the scientific community and has not yet received scientific recognition;
- heredity. According to studies, the risk of developing myeloid leukemia is greater in people with chromosomal disorders (Down syndrome, Klinefelter syndrome, etc.);
- treatment with certain drugs that are intended for the treatment of tumors against the background of radiation. Also, the risk of getting sick is increased by aldehydes, alkenes, alcohols, smoking. 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 red cell chromosomes in the bone marrow is disturbed, new DNA appears, the structure of which is abnormal. Further, abnormal cells are cloned, gradually displacing normal cells, up to a situation where the number of abnormal clones does not begin to strongly 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 released into the bloodstream, abnormal white blood cells do not perform the main task, leaving the body without protection. Therefore, a person who develops chronic myelogenous 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 below.
The chronic phase lasts about 4 years. It is at this time that the patient, as a rule, turns to the doctor. In the chronic stage, the disease is characterized by stability, so the symptoms in a minimal amount can hardly bother a person. It happens that the disease is discovered randomly during the next blood test.
The accelerative phase lasts about a year and a half. At this time, the pathological process is activated, the number of immature leukocytes in the bloodstream increases. With the right choice of therapy, timely response, it is possible to return the disease to the chronic phase.
The terminal phase (blast crisis) lasts less than six months and ends fatally. The stage is characterized by an exacerbation of symptoms. At this time, the red cells of the bone marrow are completely replaced by abnormal clones of a malignant nature.
Myeloid leukemia symptoms
Depending on the stage at which chronic myeloid leukemia is currently located, the symptoms will differ. Nevertheless, it is possible to determine the common features inherent in the disease at different stages. Patients clearly expressed lethargy, weight loss, loss of appetite. As the disease progresses, the spleen and liver enlarge, and the skin becomes pale. Patients are concerned about pain in the bones, at night - excessive sweating.
As for the symptoms of each phase, for the chronic stage, the characteristic signs will be: deterioration in well-being, loss of strength, weight loss. During meals, patients quickly feel full, pain often occurs in the left area of the abdomen. Rarely in the chronic phase, patients complain of shortness of breath, headaches, and visual disturbance. 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 a deterioration in the picture of the disease. The person often has a fever for no apparent reason. The temperature can rise to 39 degrees, a person feels trembling. Possible bleeding through the mucous membranes, skin, intestines. A person feels a sharp weakness, exhaustion. The spleen enlarges as much as possible, gives pain in the left side of the abdomen and a feeling of heaviness. As mentioned above, after the terminal stage, death follows. Therefore, it is better to start treatment as early as possible.
Diagnosis of myeloid leukemia
A hematologist can establish myeloid leukemia in a person. He conducts a visual examination, listens to complaints and sends the patient to an ultrasound of the abdomen, a blood test. Additionally, biochemistry, biopsy, bone marrow puncture, cytochemical studies are performed. The blood picture in the results of the analysis 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).
Myeloid leukemia treatment
How exactly to treat the disease, the doctor determines taking into account the stage of the disease, the presence of contraindications, concomitant diseases, age. If the disease proceeds without any special symptoms, then for the treatment of a condition such as chronic myeloid leukemia, treatment is prescribed in the form of general strengthening agents, nutrition correction, taking vitamin complexes, and regular monitoring in a dispensary. According to scientists, a-interferon has a positive effect on the condition of patients.
With regard to the appointment of drugs, then with the results of tests for leukocytes 30-50 * 109 / l, the patient is prescribed myelosan in an amount of 2-4 mg / day. With an increase in indicators to 60-150 * 109 / l, the dose of the drug rises to 6 mg / day. If leukocytosis exceeds the indicated values, the daily dose of myelosan is increased to 8 mg. The effect will be noticeable approximately on the 10th day from the start of therapy. The hemogram will normalize against the background of a decrease in the size of the spleen around the time of 3-6 weeks of therapy, when the total dose of the drug is 250 mg. Further, 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 an exacerbation of the process, if the number of leukocytes rises to 20-25 * 109 / l against the background of an enlarged spleen.
Radiation therapy (irradiation) is given as the primary treatment in some cases where splenomegaly becomes the main symptom. Irradiation is prescribed only if the level of leukocytes in the analyzes is above 100 * 109 / l. As soon as the indicator drops to 7-20 * 109 / l, the irradiation is stopped. After about a month, melosan is prescribed to support the body.
During the treatment of the progressive phase of chronic myeloid leukemia, mono- and polyvide chemotherapy is prescribed. If the analyzes show significant leukocytosis, and myelosan does not give an effect, myelobromol is prescribed at 125-250 mg per day, controlling peripheral blood parameters. After about 2-3 weeks, the hemogram returns to normal, after which maintenance therapy can be started 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 work. In this case, dopan is taken 6-10 mg every 4-10 days (as prescribed by a doctor). The interval between doses of 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 canceled. It is best to take the medicine after dinner, and then take sleeping pills. This is due to the possibility of the appearance of dyspeptic phenomena. For maintenance therapy, the doctor may prescribe dopam at a dosage of 6-10 mg once every 2-4 weeks, monitoring the hemogram.
If doctors observe that the disease is resistant to dopan, myelosan, myelobromol and radiation, then the patient is prescribed hexaphosphamide. If in the test results the number of leukocytes reaches 100 * 109 / l, then hexaphosphamide is prescribed 20 mg daily, with indicators of 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 indicators drop to 10-15 * 109 / l, the treatment with the drug is stopped. The course of treatment is usually designed for a dose of 140-600 mg for 10-30 days. Positive results from drug treatment are observed, as a rule, after 1-2 weeks. If it is necessary to carry out maintenance therapy, hexaphosphamide is prescribed 10-20 mg every 5-15 days. The doctor prescribes the intervals individually, taking into account the dynamics of treatment, the patient's state of health.
For the treatment of the progressive phase of chronic myeloid leukemia, the AVAMP and CVAMP drug programs are prescribed. The AVAMP program consists of two 10-day courses with a 10-day break. The list of drugs includes : cytosar (30 mg/m intramuscularly on days 1 and 8), methotrexate (12 mg/m intramuscularly on days 2, 5 and 9), vincristine (1.5 mg/m intravenously on days 3 and 10), 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 AVAMP program is a whole course of drugs by analogy with the previous program, but instead of cytosar intramuscularly, cyclophosphamide is prescribed 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, hydroxycarbamide is prescribed. It has contraindications: leukopenia (the number of leukocytes is below 3*109/l) and thrombocytopenia (platelets in the analyzes are less than 100*109/l). First, the drug is prescribed at 1600 mg / m every day. If the number of leukocytes in the blood becomes less than 20 * 10 / l, then the drug is prescribed at 600 mg / m, and if the number of leukocytes drops to 5 * 109 / l, the drug is canceled.
In the case of resistance to cytostatics and the progression of myeloid leukemia, doctors may prescribe leukocytapheresis in parallel with one of the above polychemotherapy regimens. Indications for leukocytapheresis are clinical manifestations of stasis in the vessels of the brain (decrease in hearing and pain in the head, a feeling of "hot flashes", heaviness in the head) against the background of hyperthrombocytosis and hyperleukocytosis.
In the stage of a blast crisis, chemotherapy is prescribed, which acts in acute leukemia. In case of anemia, infectious complications, transfusion of erythrocyte mass, thromboconcentrate and antibiotic therapy are prescribed.
If a patient is diagnosed with extramedullary tumor formations (glands that overlap the larynx, etc.), which threaten his life, then radiation therapy is prescribed.
Bone marrow transplantation is used in the case of chronic myelogenous leukemia in the chronic phase. Thanks to transplantation, remission occurs in about 70% of patients.
Splenectomy in the case of chronic myeloid leukemia is prescribed for rupture of the spleen and a condition that is fraught with rupture. Indications can be: a severe condition of discomfort in the abdomen, which is associated with the huge size of the spleen, as well as pain syndrome against the background of repeated perisplenitis, deep thrombocytopenia, hemolytic crisis, wandering spleen syndrome with the risk of twisting the legs.
Prognosis for chronic myeloid leukemia
The disease is a life-threatening condition. Most patients say goodbye to life at the accelerating and terminal stages of the disease. Up to about 10% of patients diagnosed with myelogenous 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 in the terminal phase, the life of the patient can last up to a year. However, at any stage of the disease one should not give up. It is likely that the statistics do not include all cases when the disease was extinguished and the life span with it was extended by several years, possibly even decades.
Chronic myeloid leukemia is a cancer of the blood, which is characterized by a decrease in the level of leukocytes and the appearance of a large number of immature cells - granulocytes.
According to statistics, the incidence of myeloid leukemia is the same in women and men, most often occurs at the age of 30-40 years.
Causes of Chronic Myeloid Leukemia
Among the main factors provoking cancer of the blood, we can distinguish:
- Hereditary predisposition - cases of blood cancer are recorded in relatives
- Genetic predisposition - the presence of congenital chromosomal mutations, such as Down syndrome, increases the likelihood of developing the disease
- Exposure to radiation
- The use of chemotherapy and radiation therapy in the treatment of other cancers can provoke myeloid leukemia
Stages of chronic myeloid leukemia
The development of chronic myeloid leukemia occurs in three successive stages:
chronic stage
The longest stage, which usually lasts 3-4 years. Most often, it is asymptomatic or with a blurred clinical picture, which does not cause suspicion of the tumor nature of the disease, either in doctors or in patients. Chronic myelogenous leukemia is detected, as a rule, with a random blood test.
Accelerative stage
At this stage, the disease is activated, the level of pathological blood cells increases at a rapid pace. The duration of acceleration is about a year.
At this stage, with proper therapy, there is a chance to return leukemia to the chronic stage.
terminal stage
The most acute stage - lasts no more than 6 months and ends lethally. At this stage, blood cells are almost completely replaced by pathological granulocytes.
Symptoms of Chronic Myeloid Leukemia
The manifestations of the disease directly depend on the stage.
Symptoms of the chronic stage:
In most cases, it is asymptomatic. Some patients complain of weakness, increased fatigue, but, as a rule, do not attach any importance to this. At this stage, the disease is detected during the next blood test.
In some cases, there may be weight loss, loss of appetite, excessive sweating, especially during a night's sleep.
With an enlarged spleen, pain may occur in the left side of the abdomen, especially after eating.
In rare cases, a bleeding tendency develops due to a decrease in platelet levels. Or, on the contrary, when they increase, blood clots form, which is fraught with myocardial infarction, stroke, visual and respiratory disorders, and headaches.
Symptoms of the accelerating stage:
As a rule, it is at this stage that the first manifestations of the disease are felt. Patients complain of poor health, severe weakness, excessive sweating and pain in the joints and bones. Worried about the increase in body temperature, increased bleeding and an increase in the abdomen due to the growth of tumor tissue in the spleen.
Diagnosis of chronic myeloid leukemia
Chronic myeloid leukemia is diagnosed by an oncologist-hematologist.
Blood tests
The main method of diagnosis. According to it, you can not only make a diagnosis, but also determine the stage of the pathological process.
At the chronic stage, in the general blood test, there is an increase in platelets and the appearance of granulocytes against the background of a decrease in the total number of leukocytes.
At the accelerating stage, granulocytes already account for 10-19% of leukocytes, the platelet count can be either increased or, on the contrary, reduced.
In the terminal stage, the number of granulocytes steadily increases, and the level of platelets falls.
A biochemical blood test is performed to analyze the functioning of the liver and spleen, which, as a rule, suffer from myeloid leukemia.
Bone marrow biopsy
For this study, bone marrow is taken with a thin needle, after which the material is sent to the laboratory for detailed analysis.
Most often, bone marrow is taken from the head of the femur, however, the calcaneus, sternum, wings of the pelvic bones can be used.
In the bone marrow, a picture similar to a blood test is observed - the number of immature leukocytes increases.
Hybridization and PCR
A study such as hybridization is necessary in order to identify an abnormal chromosome, and PCR is an abnormal gene.
Cytochemical study
The essence of the study is that when special dyes are added to blood samples, certain reactions are observed. According to them, the doctor can not only determine the presence of a pathological process, but also conduct a differential diagnosis between chronic myeloid leukemia and other variants of blood cancer.
In a cytochemical study in chronic myeloid leukemia, a decrease in alkaline phosphatase is observed.
Cytogenetic studies
This study is based on the study of the patient's genes and chromosomes. For this, blood is taken from a vein, which is sent for a special analysis. The result, as a rule, is ready only after a month.
In chronic myeloid leukemia, the so-called Philadelphia chromosome is found - the culprit in the development of the disease.
Instrumental research methods
Ultrasound, computed and magnetic resonance imaging are necessary for the diagnosis of metastases, the state of the brain and internal organs.
Treatment of chronic myeloid leukemia
Bone marrow transplantation offers a real chance of recovery for patients with chronic myelogenous leukemia.
This treatment option consists of several successive stages.
Finding a bone marrow donor. The most suitable donor for transplantation are close relatives. If a suitable candidate is not found among them, it is necessary to look for such a person in special donor banks.
Once it is found, various compatibility tests are carried out to make sure that the donor material will not be aggressively perceived by the patient's body.
Preparing the patient for surgery lasts 1-1.5 weeks. At this time, the patient undergoes chemotherapy and radiation therapy.
Bone marrow transplantation.
During the procedure, a catheter is inserted into the patient's vein, through which stem cells enter the bloodstream. They settle in the bone marrow and after a while begin to work there. To prevent the main complication - rejection - drugs are prescribed to suppress the immune system and prevent inflammation.
Decreased immunity. From the moment of introduction of stem cells to the start of their work in the patient's body, as a rule, it takes about a month. At this time, under the influence of special preparations, the patient's immunity is reduced, this is necessary to prevent rejection. However, on the other hand, it creates a high risk of infection. The patient must spend this period in a hospital, in a special ward - he is protected from contact with a possible infection. Antifungal and antibacterial agents are prescribed, body temperature is constantly monitored.
Engraftment of cells. The patient's well-being gradually begins to improve and return to normal.
Recovery of bone marrow function takes several months. Throughout this period, the patient is under the supervision of a doctor.
Chemotherapy
In chronic myeloid leukemia, several groups of drugs are used:
Hydroxyurea preparations inhibiting DNA synthesis in tumor cells. Side effects may include digestive disorders and allergies.
Of the modern drugs, protein tyrosine kinase inhibitors are often prescribed. These drugs inhibit the growth of pathological cells, stimulate their death, and can be used at any stage of the disease. Side effects may include cramps, muscle pain, diarrhea, and nausea.
Interferon is prescribed after the normalization of the number of leukocytes in the blood to suppress the formation and growth and restore the patient's own immunity.
Possible side effects include depression, mood swings, weight loss, autoimmune pathologies and neuroses.
Radiation therapy
Radiation therapy for chronic myeloid leukemia is carried out in the absence of the effect of chemotherapy or in preparation for bone marrow transplantation.
Gamma irradiation of the spleen helps to slow down the growth of the tumor.
Splenectomy
In rare cases, removal of the spleen or, in medical terms, a splenectomy may be prescribed. Indications for this are a sharp decrease in platelets or severe pain in the abdomen, a significant increase in the body or the threat of its rupture.
Leukocytophoresis
A significant increase in leukocytes can lead to serious complications, such as microthrombosis and retinal edema. In order to prevent them, the doctor may prescribe leukocytophoresis.
This procedure is similar to the usual blood purification, only in this case, tumor cells are removed from it. This improves the patient's condition and prevents complications. Leukocytophoresis can also be used in combination with chemotherapy to improve the effect of the treatment.
Chronic myeloid leukemia is an oncological process that originates in immature cells of the hematopoietic tissue located in the spleen parenchyma and bone marrow. This disease is dangerous for human life, because its development is accompanied by a pathological change in the blood, leading to an early death. If a patient has chronic myelogenous leukemia, emergency medical care is required.
Chronic oncological damage to myeloid hematopoietic cells, precursors of granular leukocytes, 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 Philadelphia.
The occurrence of this kind of mutation occurs as follows:
- due to the influence of certain negative factors on the human body, the abl genes from the 9th chromosome and bcr from the 22nd chromosome merge;
- a pathological compound provokes the formation of an abnormal ABL-BCR protein, which activates the process of malignancy of a blood cell;
- the blast cell mutated due to a chromosomal disorder, the future myeloid granular leukocyte, stops 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 erythrocytes, which completely disrupts the functioning of the circulatory system.
The occurrence of such a violation in the DNA of leukocytes and an uncontrolled increase in the blood of abnormal cells leads to the development of an oncological disease 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 by specific symptoms for a long time 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 frequency of diagnosis is only 1-5% of clinical cases of all childhood leukemias.
This pathological condition can occur in a small child in one of two types:
- Juvenile (related to adolescence) chronic myelogenous leukemia. This type of disease is considered "adult" and prevails in children after 5 years. 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 affects mainly babies under the age of two and differs from the juvenile form in the absence of an abnormal chromosome in blast cells. Another characteristic feature of this type of disease is a pronounced decrease in the number of leukocytes in the blood of sick children already at an early stage of development of the pathological condition, which leads to frequent bleeding, which is very difficult to stop.
Worth knowing! The younger the child, the more severe 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
Chronic myeloid leukemia in clinical practice 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 passes through 3 phases, each of which is characterized by certain clinical signs and morphological changes in the blood:
- 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 tissues 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 accidental finding.
- Acceleration phase, or transitional. At this stage, clinical symptoms are mild and the condition of patients can be considered stable. Only histological signs undergo changes - an increase in the quantitative composition of leukocytes and myelocytes begins.
- 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 always accompanies the final phase, is the infarction of the spleen and its obvious increase due to the accumulation of a large number of blast cells in the hematopoietic organ. More than half of patients in this phase of the disease have fibrosis (tissue enlargement) of the bone marrow.
Worth knowing! It is usually possible to identify chronic myeloid leukemia of the bone marrow, spleen and blood in the last phase of the disease, which is associated with the absence of specific symptoms at the 1st and 2nd stages. Such insidiousness of the disease leads to frequent deaths, but its slow development, which can last for many years, brightens up this picture, because in many patients it is possible to identify a pathological condition in the early phase, when diagnosing another disease.
Causes that provoke the development of blood pathology
Chronic myeloid leukemia is the first and only oncological disease, the cause of which 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 has arisen as a result of such a genetic mutation develops very slowly, and a person can live to old age without knowing about the presence of oncological pathology in his blood. But the development of chronic myeloid leukemia is also rapid.
Quickly, in a few months, the disease can reach the final phase if certain risk factors are present in a person’s life, the main of which are:
- living in areas with high background radiation or areas in close proximity to nuclear power plants;
- long-term treatment with cytostatics or uncontrolled intake of antibacterial drugs with increased toxicity;
- regular, continuing for a long time, exposure to the human body of toxic and chemical substances;
- the presence in the anamnesis of a person of Klinefelter's or Down's syndromes.
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 disorders appear, consult a specialist for advice. Also, people at risk are recommended annual preventive diagnostics. Timely detection of pathological changes in the composition of the blood allows you to completely cure the developing chronic form of myeloid leukemia.
Symptoms of oncopathology of hematopoietic organs
Signs of the disease are absent for a long time, the first specific symptoms of chronic myelogenous leukemia, which make a person 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 blurred, mild symptoms. But knowing them, one can suspect the development of a pathological condition and, having turned to a hemato-oncologist in a timely manner, diagnose chronic myeloid leukemia in an early phase that is well amenable to therapy.
The main signs that should cause concern 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, since they may indirectly indicate a developing blood oncology. 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.
Diagnosis includes laboratory and instrumental methods to confirm or refute the development of the disease.
If you suspect chronic myeloid leukemia, the doctor first of all collects an anamnesis and conducts a physical examination, which allows you to detect changes in the skin, enlarged lymph nodes, spleen and liver, indirectly indicating the presence of a pathological process of malignancy in the human hematopoietic system. In the presence of these signs, patients with suspected development of chronic myeloid leukemia are referred for 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 the biological fluid is fixed;
- histological examination of biopsy material taken by fine needle puncture from the bone marrow.
All patients are prescribed an additional one to clarify the nature of the course of chronic myelogenous leukemia. The most informative in this disease have radiography, ultrasound of the abdominal cavity, CT and MRI. Using these techniques, specialists not only clarify the nature of the oncological process, but also reveal the presence of secondary malignant foci.
Informative video
Types of therapy for chronic myeloid leukemia: drug, surgical, 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 the development of the disease, the general signs that characterize its course and the severity of the clinical picture accompanying chronic myelogenous leukemia.
Therapeutic measures are assigned individually to each patient, depending on the stage of the course of the disease:
- In the initial, chronic phase, no special treatment is required. To maintain a stable condition in patients, they are prescribed general strengthening therapy, which consists in correcting nutrition, reducing physical activity and observing the regime of work and rest.
- The activation phase of chronic myeloid leukemia requires the expansion of therapeutic measures. Patients must undergo courses of biological therapy with Interferon and chemistry with Chlorethylaminouracil, Hexaphosphamide or Mitobronitol. According to indications it can be appointed.
- With the onset of a blast crisis, treatment becomes useless. In this final phase of the disease, patients are treated exclusively with symptomatic therapy, which makes it possible to alleviate the painful symptoms of the disease and maintain the quality of life until the last days.
Recovery forecasts
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, because the timely detection of the disease presents serious difficulties. Most patients die in the transitional or terminal phase of chronic myelogenous leukemia. From the diagnosis of the disease to the onset of death at these stages of the disease takes about two years. Of particular danger is the beginning of a 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
To date, there are no specific preventive measures to prevent chronic myeloid leukemia. The only thing that hemato-oncologists advise people who are at risk for the development of an oncological process in the hematopoietic organs is regular screening.
- with the inclusion in the daily menu of dishes enriched with vitamin and mineral complexes;
- complete rejection of addictions (smoking, alcohol abuse, evening overeating), or minimizing them;
- maintaining an active, healthy lifestyle with regular exercise in feasible sports;
- reducing exposure to ultraviolet radiation: avoiding exposure to direct sunlight.
Informative video
Myeloid leukemia is a malignant degeneration of stem cells in the bone marrow, which is responsible for the production of blood cells - red and white blood cells and platelets. With myeloid leukemia (leukemia,) the bone marrow produces blast, immature cells, which, gradually, displace normal shaped elements from the bloodstream.
The disease is predominantly chronic and affects mainly adults. A blood test for myeloid leukemia is required to make a diagnosis. Since significant changes occur at different stages of the disease, it is required to conduct analyzes several times. If myeloid leukemia is suspected, doctors recommend regular examinations.
The reasons
Myeloid leukemia is the result of a mutation in the bone marrow. The abnormal cell loses its ability to function normally and begins to spontaneously divide. Cancer cells, multiplying, gradually crowd out healthy ones. As a result, anemia occurs and the body loses its defense against infections. Leukemia cells penetrate the lymph nodes, cooperate in tumors and provoke pathological processes.
The cause of multiple myeloma can be radioactive radiation or exposure to carcinogens, among which are drugs, paint thinners, rodent and insect control agents.
Hereditary factors in leukemia, as in other diseases, take place. In families where relatives fall ill with multiple myeloma, the probability of diseases among descendants is high. It is not the disease itself that is transmitted to children, but the predisposition to it.
There is a hypothesis about the infectious etiology of the disease. In this case, the race and place of residence of a person matters.
Diagnostics
A preliminary diagnosis of myelogenous leukemia is made on the basis of the results, a standard diagnostic procedure for any disease. The doctor should be alerted by an increase in the number of leukocytes.
For multiple myeloma, first of all, it should take into account the number of leukocytes and their ratio with the calculation of the leukocyte formula. When calculating the leukocyte formula, there is a shift to the left, the appearance of promyelocytes. The percentage of basophils and eosinophils is growing,. The number of platelets is normal, or slightly increased. Mild anemia symptoms are observed.
If myeloid leukemia progresses, change. Therefore, it is necessary to repeat the blood test for myeloid leukemia after a while. The results of the studies reveal severe anemia, the formed elements change size and deform (anisocytosis and poikilocytosis); the number of leukocytes increases many times in comparison with previous results. The number of blast cells reaches 15%. and erzinophils exceeds the norm. The action of alkaline phosphatase in neutrophils is blocked.
Symptoms associated with myeloid leukemia are liver problems, confirmed by an increase in the activity of serum enzymes - alanine aminotransferase and alkaline phosphatase.
Symptoms
The symptoms of myeloid leukemia are:
- Pain in the bones. The femurs, spine, pelvis, ribs hurt;
- Pathological fractures;
- Hypercalcemia. Manifested by vomiting, nausea, constipation, polyuria. There may be brain disorders, the person falls into lethargy or coma;
- Kidney diseases. Nephropathy manifests itself in the form of an increase in the content of calcium and uric acid in the blood, the appearance of protein in the urine;
- Anemia is normochromic. normally, ESR rises sharply;
- Osteoporosis;
- Compression of the spinal cord by tumors of the spine. It manifests itself in the form of back pain, aggravated by coughing, sneezing. The work of the bladder and intestines is disturbed .;
- Vulnerability to bacterial infections. Associated with a weakened immune system;
- Hemorrhages. , uterus, gums, subcutaneous hemorrhages.
Preparation for analysis
The rules for donating blood for a general analysis do not provide for specific rules for preparation. How to take a blood test for chronic myeloid leukemia is known. , in the morning, to avoid "interference" that distorts the results. On the day before blood donation, heavy physical exertion is not recommended. It is highly undesirable, within three days before the procedure, the use of fatty and fried foods. If these conditions are met, then a diagnostic blood test for myeloid leukemia will be extremely informative.
Make or finger. Venous blood is more concentrated than capillary blood, which is why some physicians require just such sampling for analysis.
Deciphering the results of myeloid leukemia takes two days from the moment the results are accepted for processing. If the laboratory is overloaded with work, then the result can be obtained later.
Provide for the taking of bone marrow samples for cytogenetic analysis from the femur. Samples are taken by biopsy or aspiration. Studying chromosomes. Affected cells contain an abnormal chromosome 22. In order to detect an abnormal chromosome, a polymerase chain reaction is used.
Treatment
The quality of the analysis is the key to successful therapy. The choice of treatment method and the intensity of the recommended procedures depend on the phase of the disease. In some patients with multiple myeloma, an increasing progression of the process is observed over many years, and does not require antitumor treatment.
In patients with metastases, local radiation therapy is used. With the slow development of myeloid leukemia, expectant tactics are used.
If the pain increases, which indicates the growth of the tumor, cytostatics are prescribed. The terms of treatment, subject to the presence of positive results, last up to two years.
Provide treatment to prevent complications. To stop hypercalcemia, corticosteroids are used against the background of heavy drinking. Medicines are used to treat kidney disease and osteoporosis.
Forecast
Myeloma in the indolent phase is not an indication for immediate treatment. The need to start therapy is the appearance of a paraprotein in the blood, or a decrease in viscosity, the presence of bleeding, bone pain, fractures, hypercalcemia, kidney damage, spinal cord compression, infectious complications.
Compression of the spinal cord requires surgical treatment, as well as local radiation. Bone fractures require orthopedic fixation.
In some cases, if radiation therapy is not indicated, cytotoxic treatment is used. In this case, it must be borne in mind that secondary myeloid leukemia can become a side effect.
If left untreated, multiple myeloma patients live up to two years. A complete cure for myeloma is the future.
Modern methods of treatment are able to slow down the destructive effect of the disease on the body and fight its specific symptoms.
RCHD (Republican Center for Health Development of the Ministry of Health of the Republic of Kazakhstan)
Version: Clinical Protocols of the Ministry of Health of the Republic of Kazakhstan - 2015
Chronic myeloid leukemia (C92.1)
Oncohematology
general information
Short description
Recommended
Expert Council
RSE on REM "Republican Center
health development"
Ministry of Health
and social development
Republic of Kazakhstan
dated July 9, 2015
Protocol #6
Protocol name: Chronic myeloid leukemia
Chronic myeloid leukemia (CML)- clonal myeloproliferative process that develops as a result of malignant transformation in early hematopoietic precursors. The cytogenetic marker of CML is the acquired chromosomal translocation t(9;22), which is called the Philadelphia chromosome (Ph+). The emergence of the Ph`-chromosome occurs as a result of the exchange of genetic material between chromosomes 9 and 22 t (9;22). As a result of the transfer of genetic material from chromosome 9 to chromosome 22, the BCR-ABL fusion gene is formed on it.
Protocol code:
ICD code -10: C92.1 - Chronic myeloid leukemia
Protocol development date: 2015
Abbreviations used in the protocol:
* - drugs purchased as part of a single import
HIV - human immunodeficiency virus
TKI - tyrosine kinase inhibitors
ELISA - enzyme immunoassay
OAM - general urinalysis
KLA - complete blood count
TCM - hematopoietic stem cell/bone marrow transplantation
CML - chronic myeloid leukemia
ECG - electrocardiogram
Ultrasound - ultrasonography
BCR - ABL - breakpoint cluster region-Abelson
CCA - Complex chromosomal aberrations
ELN - European Leukemia Net
FISH - Fluorescence in situ hybridization (Fluorescence in situ hybridization)
RT-Q-PCR - Real-Time Quantitative Reverse Transcription PCR
Nested PCR - Nested polymerase chain reaction
HLA - Human leukocyte antigen (human leukocyte antigen)
Ph - Philadelphia chromosome
WHO - World Health Organization.
Protocol Users: therapists, general practitioners, oncologists, hematologists.
Level of Evidence Scale
| Level of Evidence | Characteristics of the studies that formed the basis of the recommendations |
| BUT | A high-quality meta-analysis, a systematic review of randomized clinical trials (RCTs), or a large RCT with a very low probability (++) of bias, the results of which can be generalized to an appropriate population. |
| AT | High-quality (++) systematic review of cohort or case-control studies or High-quality (++) cohort or case-control studies with a very low risk of bias or RCTs with a low (+) risk of bias, the results of which can be extended to the appropriate population. |
| FROM | Cohort or case-control or controlled trial without randomization with a low risk of bias (+), the results of which can be generalized to the appropriate population or RCTs with a very low or low risk of bias (++ or +), the results of which are not can be directly extended to the relevant population. |
| D | Description of a series of cases or |
| uncontrolled study or | |
| Expert opinion |
Classification
Clinical classification:
During CML, 3 phases are distinguished: chronic, transitional (acceleration phase) and terminal phase (blast transformation or blast crisis). Criteria for acceleration phases and blast crisis are presented in the table.
Criteria for acceleration phases and blast crisis according to WHO and ELN
| Options | Acceleration phase | blast crisis phase | ||
| WHO | ELN | WHO | ELN | |
| Spleen | increase in size despite ongoing therapy | Not applicable | Not applicable | Not applicable |
| Leukocytes | an increase in the number of leukocytes (> 10x109 l) in the blood despite ongoing therapy | Not applicable | Not applicable | Not applicable |
| Blasts, % | 10-19 | 15-29 | ≥20 | ≥30 |
| Basophils, % | >20 | >20 | Not applicable | Not applicable |
| Platelets, x 109/l |
>1000 uncontrolled by therapy <100 неконтролируемые терапией |
Not applicable | Not applicable | Not applicable |
| CCA/Ph+1 | Available | Available | Not applicable | Not applicable |
| Extramedullary lesions2 | Not applicable | Not applicable | Available | Available |
1 - clonal chromosomal abnormalities in Ph+ cells
2 - excluding the liver and spleen, including lymph nodes, skin, central nervous system, bones and lungs.Clinical picture
Symptoms, course
Diagnostic criteria for diagnosis
:
the presence of the Philadelphia chromosome (balanced translocation t (9; 22) (q34; q11) according to the standard cytogenetic study of the bone marrow 1
presence of the BCR-ABL gene in bone marrow or peripheral blood cells according to molecular genetic methods (FISH, real-time polymerase chain reaction);
myeloproliferative syndrome - neutrophilic leukocytosis with a shift to the left to blasts (up to 10%) with the presence of all transitional forms (there is no "leukemic failure"), basophilic-eosinophilic association, in some cases thrombocytosis, in the myelogram - hypercellular bone marrow, hyperplasia of the erythroid germ, splenomegaly (in 50% of patients in the early chronic phase).
Complaints:
· weakness;
· sweating;
· fatigue;
subfebrile condition;
· chilling;
pain in the bones or joints;
Decrease in body weight;
hemorrhagic rashes in the form of petechiae and ecchymosis on the skin;
epistaxis;
menorrhagia;
Increased bleeding
swollen lymph nodes;
pain and heaviness in the left upper abdomen (enlarged spleen);
heaviness in the right hypochondrium.
Anamnesis:
attention should be paid to:
Long-lasting weakness
fast fatigue;
frequent infectious diseases;
Increased bleeding
the appearance of hemorrhagic rashes on the skin and mucous membranes;
enlargement of the liver, spleen.
Physical examination:
pallor of the skin;
hemorrhagic rashes - petechiae, ecchymosis;
shortness of breath
· tachycardia;
Enlargement of the liver
Enlargement of the spleen
Enlargement of lymph nodes.
1 - In approximately 5% of cases of CML, the Philadelphia chromosome may be absent and the diagnosis is verified only on the basis of data from molecular genetic methods - FISH or polymerase chain reaction (detection of the chimeric BCR-ABL gene)
Diagnostics
The list of basic and additional diagnostic measures:
The main (mandatory) diagnostic examinations carried out at the outpatient level:
UAC;
myelogram;
biochemical blood test (uric acid);
X-ray of the chest organs.
Additional diagnostic examinations performed at the outpatient level:
bone marrow examination by FISH (t(9;22)/BCR/ABL);
ELISA for HIV markers;
ELISA for markers of herpes group viruses;
Reberg-Tareev test;
· OAM;
· coagulogram;
· HLA typing;
ECG;
Echo - cardiography;
CT scan of the thoracic and abdominal segments with contrast.
The minimum list of examinations that must be carried out when referring to planned hospitalization:
UAC;
blood type and Rh factor;
biochemical blood test (total protein, albumin, globulins, level, uric acid, creatinine, urea, LDH, ALT, AST, total and direct bilirubin);
Ultrasound of the abdominal organs and spleen, peripheral lymph nodes;
X-ray of the chest organs.
The main (mandatory) diagnostic examinations carried out at the hospital level:
KLA with counting platelets and reticulocytes;
biochemical blood test (total protein, albumin, globulins, IgA, IgM, IgG, uric acid, creatinine, urea, LDH, ALT, AST, total and direct bilirubin);
Ultrasound of peripheral lymph nodes, abdominal organs, incl. spleen;
X-ray of the chest organs;
myelogram;
Cytogenetic study of the bone marrow;
bone marrow examination by FISH (t (9; 22)/BCR/ABL);
ELISA and PCR for markers of viral hepatitis;
ELISA for HIV markers;
ECG;
Echocardiography;
Reberg-Tareev test;
· OAM;
· coagulogram;
blood type and Rh factor;
· HLA typing.
Additional diagnostic examinations carried out at the hospital level:
pro-BNP (atrial natriuretic peptide) in blood serum;
bacteriological examination of biological material;
cytological examination of biological material;
Immunophenotyping of peripheral blood/bone marrow on a flow cytofluorimeter (acute leukemia panel);
Histological examination of the biopsy specimen (lymph node, iliac crest);
PCR for viral infections (viral hepatitis, cytomegalovirus, herpes simplex virus, Epstein-Barr virus, Varicella / Zoster virus);
radiography of the paranasal sinuses;
radiography of bones and joints;
FGDS;
· Ultrasound of blood vessels;
bronchoscopy;
colonoscopy;
daily monitoring of blood pressure;
daily ECG monitoring;
spirography.
Diagnostic measures taken at the stage of emergency medical care:
collection of complaints and anamnesis of the disease;
physical examination.
Instrumental Research:
· Ultrasound of the abdominal organs, lymph nodes: an increase in the size of the liver, spleen, peripheral lymphadenopathy.
· CT scan of the thoracic segment: to exclude infiltration of the lung tissue.
· ECG: violation of the conduction of impulses in the heart muscle.
· EchoCG: to exclude heart defects, arrhythmias and other diseases in patients, accompanied by damage to the heart.
· FGDS: leukemic infiltration of the mucous membrane of the gastrointestinal tract, which can cause ulcerative lesions of the stomach, duodenum 12, gastrointestinal bleeding.
· Bronchoscopy: detection of the source of bleeding.
Indications for consultation of narrow specialists:
Doctor for X-ray endovascular diagnostics and treatment - installation of a central venous catheter from a peripheral access (PICC);
hepatologist - for the diagnosis and treatment of viral hepatitis;
· gynecologist - pregnancy, metrorrhagia, menorrhagia, consultation when prescribing combined oral contraceptives;
dermatovenereologist - skin syndrome
infectious disease specialist - suspicion of viral infections;
cardiologist - uncontrolled hypertension, chronic heart failure, cardiac arrhythmia and conduction disturbances;
· neuropathologist acute cerebrovascular accident, meningitis, encephalitis, neuroleukemia;
neurosurgeon - acute cerebrovascular accident, dislocation syndrome;
nephrologist (efferentologist) - renal failure;
oncologist - suspicion of solid tumors;
otorhinolaryngologist - for the diagnosis and treatment of inflammatory diseases of the paranasal sinuses and middle ear;
Ophthalmologist - visual impairment, inflammatory diseases of the eye and appendages;
proctologist - anal fissure, paraproctitis;
psychiatrist - psychoses;
psychologist - depression, anorexia, etc.;
· resuscitator - treatment of severe sepsis, septic shock, acute lung injury syndrome in differentiation syndrome and terminal states, installation of central venous catheters.
rheumatologist - Sweet's syndrome;
Thoracic surgeon - exudative pleurisy, pneumothorax, pulmonary zygomycosis;
· transfusiologist - for the selection of transfusion media in case of a positive indirect mantiglobulin test, transfusion failure, acute massive blood loss;
Urologist - infectious and inflammatory diseases of the urinary system;
phthisiatrician - suspicion of tuberculosis;
surgeon - surgical complications (infectious, hemorrhagic);
· maxillofacial surgeon - infectious and inflammatory diseases of the dento-jaw system.
Laboratory diagnostics
Laboratory research:
· General blood analysis: leukocytes, erythrocytes and platelets are counted. Absolute neutrophilic leukocytosis with a shift of the nuclear formula to the left (up to promyelocytes or blasts), the absence of a leukemic dip, and a basophilic-eosinophilic association are characteristic. At the onset of the disease, the hemoglobin level may be within the normal range or elevated, and moderate thrombocytosis may be observed. In the phase of acceleration and blast crisis, thrombocytopenia and anemia may develop.
· Blood chemistry: there is an increase in LDH activity, hyperuricemia.
· Morphological study: in a bone marrow aspirate hypercellular bone marrow, an increase in the number of blasts, basophils and eosinophils.
· Immunophenotyping: is carried out to determine the immunophenotype of blasts in their excess (more than 20-30%).
Differential Diagnosis
differential diagnosis.
The diagnosis of chronic myeloid leukemia in classical cases is not difficult. Difficulties usually arise in the initial period of the disease, when there are still no clear leukemic changes in the blood and pronounced signs of systemic metaplasia in the organs.
The main pathognomonic sign of the disease is the detection of the Philadelphia chromosome (t(9;22)) and the chimeric BCR/ABL gene during cytogenetic examination.
Differential diagnosis can be carried out with a myeloid-type leukemoid reaction that occurs with various infections (sepsis, tuberculosis) and some tumors (Hodgkin's lymphoma, solid tumors), as well as other chronic myeloproliferative diseases. The main diagnostic criteria for chronic myelogenous leukemia are:
- the presence of anemia, not characteristic of a leukemoid reaction;
- an increase in the number of basophils and eosinophils in the leukogram;
- sometimes hyperthrombocytosis;
- myelogram data, which in myeloid leukemia is characterized by an increase in the number of myelokaryocytes and a sharp shift to the left, while with a leukemoid reaction, the myelogram is little changed;
- dynamics of the blood picture (the leukemoid reaction usually disappears with the elimination of the cause that caused it, while changes in the blood with myeloid leukemia are steadily progressing).
- the presence in chronic myelosis of intermediate forms between "powerful" elements and mature granulocytes, while "leukemic gaping" is characteristic of acute leukemia;
- the presence of an eosinophilic-basophilic association, which is absent in acute leukemia;
- sometimes observed in chronic myelosis hyperthrombocytosis, while in acute leukemia already from the very beginning there is thrombocytopenia.
Treatment abroad
Get treatment in Korea, Israel, Germany, USA
Get advice on medical tourism
Treatment
Treatment goals:
Obtaining hematological remission, cytogenetic and molecular response.
Treatment tactics:
Non-drug treatment.
Mode: general protection.
Diet: neutropenic patients are advised not to follow a specific diet ( level of evidence B).
Transfusion support
Prophylactic transfusions of apheresis virus-inactivated, preferably irradiated platelets are performed when thrombocytopenia is less than 10x109/l or at a level of less than 20x10 9 /l in case of fever or planned invasive procedures. (level of evidence D)
In patients resistant to platelet transfusions, screening for HLA antibodies and individual selection of platelets is necessary.
Transfusions of leukofiltered, preferably irradiated red blood cells are performed in the presence of poor tolerance of anemia (weakness, dizziness, tachycardia), especially in the presence of symptoms at rest. (level of evidence D)
Indications for transfusion therapy are determined primarily by clinical manifestations individually for each patient, taking into account age, comorbidities, chemotherapy tolerance and the development of complications at previous stages of treatment.
Laboratory indicators for determining indications are of secondary importance, mainly for assessing the need for prophylactic transfusions of platelet concentrate.
Indications for transfusions also depend on the time after the course of chemotherapy - the predicted decline in rates in the next few days is taken into account.
Erythrocyte mass/suspension (level of evidenceD):
· Hemoglobin levels do not need to be increased as long as normal reserves and compensation mechanisms are sufficient to meet tissue oxygen needs;
· There is only one indication for transfusion of red blood cells in chronic anemia - symptomatic anemia (manifested by tachycardia, dyspnea, angina pectoris, syncope, denovo depression or ST elevation);
· A hemoglobin level of less than 30 g/l is an absolute indication for erythrocyte transfusion;
In the absence of decompensated diseases of the cardiovascular system and lungs, hemoglobin levels may be indications for prophylactic transfusion of erythrocytes in chronic anemia:
Platelet concentrate (level of evidenceD):
· If the level of platelets is less than 10 x 10 9 /l, transfusion of apheresis platelets is performed in order to maintain their level at least 30-50 x 10 9 /l, especially in the first 10 days of the course.
· In the presence of a high risk of hemorrhagic complications (age over 60 years, increased creatinine more than 140 µmol/l), it is necessary to maintain a platelet level of more than 20 x10 9 /l.
Fresh frozen plasma (level of evidenceD):
· FFP transfusions are performed in patients with bleeding or before invasive interventions;
· Patients with an INR of ³2.0 (for neurosurgical interventions of ³1.5) are considered as candidates for FFP transfusion when planning invasive procedures.
Medical treatment:
During the examination, until the results of a cytogenetic study confirming the presence of the Ph + chromosome in the bone marrow cells, the patient is prescribed hydroxycarbamide. The dose of the drug is determined taking into account the number of leukocytes and the weight of the patient. With leukocytosis more than 100 x10 9 /l, hydrea is prescribed at a dose of 50 mcg / kg daily. Further, with a decrease in the number of leukocytes in the blood, the dose of hydrea is reduced: with leukocytosis 40-100 x10 9 / l, 40 mg / kg is prescribed, at 20-40 x 10 9 / l - 30 mg / kg, at 5 - 20 x 10 9 / l - 20 mg/kg daily.
Imatinib can be started at any WBC count. Imatinib is given (in the chronic phase) at a dose of 400 mg/day orally after meals.
To obtain stable results, taking imatinib should be constant, long-term. Doses of imatinib are adjusted according to the severity of complications. It is necessary to take into account the toxicity of therapy in this patient (table 2).
Table 2. Hematological Toxicity Scale
| Index | DEGREE OF TOXICITY | ||||
| 0 | 1 | 2 | 3 | 4 | |
| Leukocytes | ≥4.0×10 9 /l | 3,0-3,9 | 2,0-2,9 | 1,0-1,9 | <1,0 |
| platelets | Norm | 75.0-norm | 50-74,9 | 25,0-49,0 | Less than 25 |
| Hemoglobin | Norm | 100-norm | 80-100 | 65-79 | Less than 65 |
| Granulocytes | ≥2.0×10 9 /l | 1,5-1,9 | 1,0-1,4 | 0,5-0,9 | Less than 0.5 |
In the chronic phase of CML, the drug is taken continuously. Breaks in treatment should be done with the development of severe hematological toxicity grade ³3.
Treatment is resumed when clinical and hematological parameters are restored (neutrophils > 1.5 thousand / μl, platelets > 75 thousand / μl). After toxicity has resolved, imatinib 400 mg is resumed if treatment is interrupted for less than 2 weeks. With repeated episodes of the development of cytopenia or if they last more than 2 weeks, it is possible to reduce the dose of imatinib to 300 mg / day. Further reduction in the dose of imatinib is not advisable. it is not possible to achieve its therapeutic concentration in the blood. Therefore, with repeated episodes of cytopenia, breaks in treatment with imatinib are taken. With the stabilization of clinical and hematological parameters within 1-3 months, it is necessary to consider the issue of resuming the drug at a dose of 400 mg / day.
Patients who previously received long-term busulfan recommended to continue taking busulfan(switching to imatinib therapy is ineffective due to the possibility of myelosuppression).
The tactics of treating patients in case of intolerance to imatinib or insufficient response to therapy, as well as in the phase of acceleration and blast crisis are presented in table 2, response criteria in tables 4 and 5.
| chronic phase | ||
| 1st line | All patients | Imatinib4 400mg daily |
|
2nd line (after imatinib) |
Toxicity, intolerance | Dasatinib or Nilotinib |
| Suboptimal response | Continue imatinib at previous or higher doses, dasatinib, or nilotinib | |
| No response |
Dasatinib or nilotinib AlloHSCT with progression to acceleration or blast crisis and in the presence of the T315I mutation |
|
| 3rd line | Suboptimal response to dasatinib or nilotinib | Continue Dasatinib or Nilotinib. In patients with prior resistance to imatinib, presence of mutations in patients with EBMT scores ≤2, consider allo-TKM |
| No response to Dasatinib or Nilotinib | alloTKM | |
| Phase of acceleration and blast crisis | ||
| 1st line therapy | Patients who did not receive TKIs | Imatinib 600 mg or 800 mg or dasatinib 140 mg or nilotinib 400 mg twice daily followed by allo-BMT |
| 2nd line therapy | Patients previously treated with imatinib | AlloTKM, nilotinib or dasatinib therapy |
4 Patients at high risk in the chronic phase of CML can use nilotinib and dasatinib in the first line of therapy (with a total score of >1.2 by Socal et al, >1480 by EURO, >87 by EUTOS - score calculator http://www .leukemia-net.org/content/leukemias/cml/eutos_score/index_eng.html , or http://www.leukemia-net.org/content/leukemias/cml/cml_score/index_eng.html). The drug is selected according to the following scheme (level of evidenceD) .
Doses of drugs(level of evidence A):
Imatinib 400 mg/day;
Nilotinib 300 mg/day;
Dasatinib 100 mg/day
Medical treatment provided on an outpatient basis:
− a list of essential medicines with an indication of the form of release (having a 100% probability of use):
Antineoplastic and immunosuppressive drugs
− imatinib 100 mg, capsules;
− nilotinib 200 mg capsules;
− dasatinib* 70mg tablets;
− hydroxycarbamide 500 mg, capsules;
- allopurinol 100 mg, tablets.
Drugs that reduce the toxic effect of anticancer drugs
· filgrastim, solution for injections 0.3 mg/ml, 1 ml;
Ondansetron, injection 8 mg/4 ml.
Antibacterial agents
azithromycin, tablet/capsule, 500 mg;
amoxicillin/clavulanic acid, film-coated tablet, 1000 mg;
levofloxacin, tablet, 500 mg;
moxifloxacin, tablet, 400 mg;
ofloxacin, tablet, 400 mg;
ciprofloxacin tablet, 500 mg;
metronidazole, tablet, 250 mg;
metronidazole, dental gel 20g;
erythromycin, 250mg tablet.
anidulafungin, lyophilized powder for solution for injection, 100 mg/vial;
voriconazole tablet, 50 mg;
Clotrimazole, solution for external use 1% 15ml;
fluconazole, capsule/tablet 150 mg.
acyclovir, tablet, 400 mg;
famciclovir tablets 500mg
sulfamethoxazole/trimethoprim 480 mg tablet.
Solutions used to correct violations of water, electrolyte and acid-base balance
· dextrose, solution for infusions 5% 250ml;
Sodium chloride, solution for infusion 0.9% 500 ml.
Heparin, injection 5000 IU/ml, 5 ml; (for flushing the catheter)
rivaroxaban tablet.
· tranexamic acid, capsule/tablet 250 mg;
Ambroxol, oral and inhalation solution, 15mg/2ml, 100ml;
atenolol, tablet 25 mg;
acetylsalicylic acid, 50 mg, 100 mg tablets
Drotaverine, tablet 40 mg;
· lactulose, syrup 667g/l, 500 ml;
Lisinopril 5mg tablet
methylprednisolone, tablet, 16 mg;
omeprazole 20 mg capsule;
prednisolone, tablet, 5 mg;
Torasemide, 10mg tablet;
fentanyl, transdermal therapeutic system 75 mcg/h; (for the treatment of chronic pain in cancer patients)
Chlorhexidine, solution 0.05% 100ml;
Medical treatment provided at the hospital level:
- a list of essential medicines with an indication of the form of release (having a 100% probability of use):
Imatinib 100mg capsules
nilotinib 200mg capsules
dasatinib* 70mg tablets;
Hydroxycarbamide 500mg capsules.
- a list of additional medicines with an indication of the form of release (less than 100% probability of use):
Drugs that weaken the toxic effect of anticancer drugs:
. filgrastim, injection 0.3 mg/ml, 1 ml;
. ondansetron, injection 8 mg/4 ml;
. allopurinol 100mg tablets.
Antibacterial agents:
azithromycin, tablet/capsule, 500 mg; lyophilized powder for solution for intravenous infusion, 500 mg;
Amikacin, powder for injection, 500 mg/2 ml or powder for solution for injection, 0.5 g;
amoxicillin/clavulanic acid, film-coated tablet, 1000 mg; powder for solution for intravenous and intramuscular administration 1000 mg + 500 mg;
Vancomycin, powder/lyophilisate for solution for infusion 1000 mg;
· gentamicin, solution for injections 80mg/2ml 2ml;
imipinem, cilastatin powder for solution for infusion, 500 mg/500 mg;
Sodium colistimethate*, lyophilisate for solution for infusion 1 million U/vial;
Levofloxacin, solution for infusion 500 mg/100 ml; tablet, 500 m;
linezolid, solution for infusion 2 mg/ml;
Meropenem, lyophilisate/powder for solution for injection 1.0 g;
metronidazole, tablet, 250 mg, solution for infusion 0.5% 100ml, dental gel 20g;
moxifloxacin, tablet, 400 mg, solution for infusion 400 mg/250 ml;
ofloxacin, tablet, 400 mg, solution for infusion 200 mg/100 ml;
piperacillin, tazobactam powder for solution for injection 4.5 g;
· tigecycline*, lyophilized powder for solution for injection 50 mg/vial;
Ticarcillin/clavulanic acid, lyophilized powder for solution for infusion 3000mg/200mg;
cefepime, powder for solution for injection 500 mg, 1000 mg;
cefoperazone, sulbactam powder for solution for injection 2 g;
· ciprofloxacin, solution for infusion 200 mg/100 ml, 100 ml, tablet 500 mg;
erythromycin, 250 mg tablet;
Ertapenem lyophilizate, for solution for intravenous and intramuscular injections 1 g.
Antifungal medicines
Amphotericin B*, lyophilized powder for solution for injection, 50 mg/vial;
anidulofungin, lyophilized powder for solution for injection, 100 mg/vial;
voriconazole, powder for solution for infusion 200 mg/vial, tablet 50 mg;
· itraconazole, oral solution 10 mg/ml 150.0;
Caspofungin, lyophilisate for solution for infusion 50 mg;
Clotrimazole, cream for external use 1% 30g, 15ml;
· micafungin, lyophilized powder for solution for injection 50 mg, 100 mg;
fluconazole, capsule/tablet 150 mg, solution for infusion 200 mg/100 ml, 100 ml.
Antiviral drugs
acyclovir, cream for external use, 5% - 5.0, tablet 400 mg;
aciclovir, powder for solution for infusion, 250 mg;
acyclovir, cream for external use, 5% - 5.0;
Valaciclovir, tablet, 500mg;
valganciclovir, tablet, 450 mg;
· ganciclovir*, lyophilisate for solution for infusion 500 mg;
famciclovir, tablets, 500 mg №14.
Drugs used for pneumocystosis
sulfamethoxazole/trimethoprim, concentrate for solution for infusion (80mg+16mg)/ml, 5ml, 480mg tablet.
Additional immunosuppressive drugs:
Dexamethasone, injection 4 mg/ml 1 ml;
· methylprednisolone, tablet, 16 mg, injection, 250 mg;
Prednisolone, injection 30 mg/ml 1 ml, tablet 5 mg.
Solutions used to correct violations of water, electrolyte and acid-base balance, parenteral nutrition
albumin, solution for infusion 10%, 100 ml, 20% 100 ml;
· water for injections, solution for injections 5 ml;
dextrose, solution for infusion 5% - 250 ml, 5% - 500 ml, 40% - 10 ml, 40% - 20 ml;
· potassium chloride, solution for intravenous administration 40 mg/ml, 10 ml;
· calcium gluconate, solution for injections 10%, 5 ml;
· calcium chloride, solution for injections 10% 5 ml;
Magnesium sulfate, injection 25% 5 ml;
Mannitol, injection 15% -200.0;
Sodium chloride, solution for infusion 0.9% 500ml, 250ml;
Sodium chloride, potassium chloride, sodium acetate solution for infusions in a 200ml, 400ml, 200ml vial;
· sodium chloride, potassium chloride, sodium acetate solution for infusions 400ml;
Sodium chloride, potassium chloride, sodium bicarbonate solution for infusions 400ml;
L-alanine, L-arginine, glycine, L-histidine, L-isoleucine, L-leucine, L-lysine hydrochloride, L-methionine, L-phenylalanine, L-proline, L-serine, L-threonine, L- tryptophan, L-tyrosine, L-valine, sodium acetate trihydrate, sodium glycerophosphate pentihydrate, potassium chloride, magnesium chloride hexahydrate, glucose, calcium chloride dihydrate, olive and soybean oil mixture emulsion for inf.: three-chamber containers 2 l;
hydroxyethyl starch (penta starch), solution for infusion 6% 500 ml;
Amino acid complex, infusion emulsion containing a mixture of olive and soybean oils in a ratio of 80:20, an amino acid solution with electrolytes, a dextrose solution, with a total calorie content of 1800 kcal 1 500 ml three-piece container.
Medicines used for intensive care (cardiotonic drugs for the treatment of septic shock, muscle relaxants, vasopressors and anesthetics):
Aminophylline, injection 2.4%, 5 ml;
· amiodarone, injection, 150 mg/3 ml;
atenolol, tablet 25 mg;
Atracurium besylate, solution for injection, 25 mg/2.5 ml;
atropine, solution for injections, 1 mg/ml;
diazepam, solution for intramuscular and intravenous use 5 mg/ml 2 ml;
dobutamine*, injection 250 mg/50.0 ml;
· dopamine, solution/concentrate for solution for injection 4%, 5 ml;
regular insulin;
· ketamine, solution for injections 500 mg/10 ml;
· morphine, solution for injections 1% 1ml;
norepinephrine*, injection 20 mg/ml 4.0;
· pipecuronium bromide, lyophilized powder for injection 4 mg;
propofol, emulsion for intravenous administration 10 mg/ml 20 ml, 50 ml;
rocuronium bromide, solution for intravenous administration 10 mg/ml, 5 ml;
sodium thiopental, powder for solution for intravenous administration 500 mg;
· phenylephrine, solution for injections 1% 1ml;
phenobarbital, tablet 100 mg;
human normal immunoglobulin, solution for infusion;
Epinephrine, injection 0.18% 1 ml.
Drugs that affect the blood coagulation system
Aminocaproic acid, solution 5% -100 ml;
. anti-inhibitor coagulant complex, lyophilized powder for injection, 500 IU;
. acetylsalicylic acid, 50 mg, 100 mg, tablets
Heparin, injection 5000 IU/ml, 5 ml;
hemostatic sponge, size 7*5*1, 8*3;
Nadroparin, injection in pre-filled syringes, 2850 IU anti-Xa/0.3 ml, 5700 IU anti-Xa/0.6 ml;
Enoxaparin, injection solution in syringes 4000 anti-Xa IU/0.4 ml, 8000 anti-Xa IU/0.8 ml.
Other medicines
bupivacaine, injection 5 mg/ml, 4 ml;
Lidocaine, solution for injection, 2%, 2 ml;
Procaine, injection 0.5%, 10 ml;
human immunoglobulin normal solution for intravenous administration 50 mg/ml - 50 ml;
· omeprazole, capsule 20 mg, lyophilized powder for solution for injection 40 mg;
famotidine, lyophilized powder for solution for injection 20 mg;
Ambroxol, solution for injection - 15 mg / 2 ml, solution for oral administration and inhalation - 15 mg / 2 ml, 100 ml;
amlodipine 5 mg tablet/capsule;
acetylcysteine, powder for oral solution, 3 g;
Heparin, gel in a tube 100000ED 50g;
Dexamethasone, eye drops 0.1% 8 ml;
Diphenhydramine, injection 1% 1 ml;
Drotaverine, injection 2%, 2 ml;
captopril, tablet 50 mg;
· ketoprofen, solution for injections 100 mg/2 ml;
· lactulose, syrup 667 g/l, 500 ml;
Levomycetin, sulfadimethoxine, methyluracil, trimecaine ointment for external use 40g;
Lisinopril 5mg tablet
· methyluracil, ointment for local use in a tube 10% 25g;
naphazoline, nose drops 0.1% 10ml;
nicergoline, lyophilisate for the preparation of an injection solution 4 mg;
povidone-iodine, solution for external use 1 l;
salbutamol, solution for nebulizer 5mg/ml-20ml;
Dioctahedral smectite, powder for oral suspension 3.0 g;
spironolactone, 100 mg capsule;
Tobramycin, eye drops 0.3% 5 ml;
Torasemide, 10mg tablet;
· tramadol, solution for injections 100 mg/2 ml;
tramadol, capsule 50 mg, 100 mg;
fentanyl, transdermal therapeutic system 75 mcg/h (for the treatment of chronic pain in cancer patients);
folic acid, tablet, 5 mg;
furosemide, solution for injection 1% 2 ml;
chloramphenicol, sulfadimethoxine, methyluracil, trimecaine ointment for external use 40g;
Chlorhexidine, solution 0.05% 100ml
Chloropyramine, injection 20 mg/ml 1 ml.
Drug treatment provided at the stage of emergency emergency care: not carried out.
Other types of treatment:
Other types of treatment provided at the outpatient level: do not apply.
Other types of treatment provided at the inpatient level:
Hematopoietic stem cell transplantation.
Carrying out allogeneic transplantation of hematopoietic stem cells can lead to a cure in patients with CML. However, this type of treatment is applicable in few patients with CML, given the high risk of complications and mortality.
When making a diagnosis and in the process of treating patients with CML, it is necessary to take into account prognostic factors that determine the life expectancy and prognosis of patients.
The relative risk in patients with CML may need to be calculated prior to initiating therapy.
Prognostic scales for patients with CML:
| Socal et al. | EURO | EUTOS[21 ] | |
| Age (years) | 0.116 (age-43.4) | 0.666 if older than 50 | Not used |
| The size of the spleen (cm) palpation below the costal arch | 0.345 x (spleen-7.51) | 0.042 x dim. spleen | 4 x size spleen |
| Platelets (x10 9 /l) | 0.188 x [(platelets/700) 2 −0.563] | 1.0956 if platelets ≥1500 | Not used |
| Blasts in blood, % | 0.887×(blasts-2.1) | 0.0584 x blasts | Not used |
| Basophils in blood, % | Not used | 0.20399 if basophils are more than 3 | 7 x basophils |
| Eosinophils in blood, % | Not used | 0.0413 x eosinophils | Not used |
| Relative Risk | Exponent of the sum | Amount x 1000 | Sum |
| Short | <0,8 | ≤780 | ≤87 |
| Intermediate | 0,8-1,2 | 781-1480 | Not used |
| High | >1,2 | >1480 | >87 |
Hammersmith 2nd generation TKI response prognostic scale
Other types of treatment provided at the stage of emergency medical care: do not apply.
Surgical intervention:
Surgical intervention provided on an outpatient basis: not carried out.
Surgical intervention provided in a hospital:
With the development of infectious complications and life-threatening bleeding, patients may undergo surgical interventions for emergency indications.
Treatment effectiveness indicators
Criteria for response to treatment and monitoring.
| Response Category | Definition | Monitoring |
|
Hematological Full |
platelets<450х10 9 /л Leukocytes<10 х10 9 /л No immature granulocytes, basophils<5% The spleen is not palpable |
At initial diagnosis, then every 15 days until a complete hematological response is achieved, then every 3 months |
|
cytogenetic Full (CCgR) 5 Partial (PCgR) Small Minimum Not |
No metaphases with Ph 1-35% Ph+ metaphases 36-65% Ph+ metaphases 66-95% Ph+ metaphases >95% Ph+ metaphases |
At diagnosis, 3 months, 6 months, then every 6 months until CCgR is achieved, then every 12 months if regular molecular monitoring is not available. Investigation should always be performed in treatment failure (primary or secondary resistance) and in unexplained anemia, thrombocytopenia and leukopenia. |
|
Molecular Full (CMR) Large (MMR) |
No BCR-ABL mRNA transcript detected by quantitative RT-PCR and/or nested PCR in two blood samples with adequate quality (sensitivity > 104) The ratio of BCR-ABLto ABL≤0.1% according to the international scale |
RT-Q-PCR: every 3 months until MMR is reached, then at least once every 6 months Mutation analysis: performed on suboptimal response or treatment failure, always before switching to another TKI |
Determination of optimal, suboptimal responses, treatment failure in primary patients with chronic phase CML receiving imatinib 400 mg/day.
| Time | Optimal Answer | Suboptimal response | Treatment failure | Attention! |
| Primary diagnosis | - | - | - |
high risk CSA/Ph+ |
| 3 months | CHR, not less than a small cytogenetic response | No cytogenetic response | Less than CHR | - |
| 6 months | Not less than PCgR | Less than PCgR | No CgR | - |
| 12 months | CCgR | PCgR | Less than PCgR | Less MMR |
| 18 months | MMR | LessMMR | Less than CCgR | - |
| Anytime during therapy | Stable or increasing MMR | Loss of MMR, mutations | CHR loss, CCgR loss, mutations, CCA/Ph+ |
Transcript boost CCA/Ph+ |
Table 6 Determination of response to treatment with second-generation TKIs as second-line therapy in patients with resistance to imatinib.
Drugs (active substances) used in the treatment
| Hemostatic sponge |
| Azithromycin (Azithromycin) |
| Allopurinol (Allopurinol) |
| Human albumin (Albumin human) |
| Ambroxol (Ambroxol) |
| Amikacin (Amikacin) |
| Aminocaproic acid (Aminocaproic acid) |
| Amino acids for parenteral nutrition + Other medicines (Fat emulsions + Dextrose + Multimineral) |
| Aminophylline (Aminophylline) |
| Amiodarone (Amiodarone) |
| Amlodipine (Amlodipine) |
| Amoxicillin (Amoxicillin) |
| Amphotericin B (Amphotericin B) |
| Anidulafungin (Anidulafungin) |
| Antiinhibitory coagulant complex (Antiingibitorny coagulant complex) |
| Atenolol (Atenolol) |
| Atracurium besylate (Atracurium besylate) |
| Acetylsalicylic acid (Acetylsalicylic acid) |
| Acetylcysteine (Acetylcysteine) |
| Acyclovir (Acyclovir) |
| Bupivacaine (Bupivacaine) |
| Valaciclovir (Valacyclovir) |
| Valganciclovir (Valganciclovir) |
| Vancomycin (Vancomycin) |
| Water for injection (Water for Injection) |
| Voriconazole (Voriconazole) |
| Ganciclovir (Ganciclovir) |
| Gentamicin (Gentamicin) |
| Heparin sodium (Heparin sodium) |
| Hydroxycarbamide (Hydroxycarbamide) |
| Hydroxyethyl starch (Hydroxyethyl starch) |
| Dasatinib (Dasatinib) |
| Dexamethasone (Dexamethasone) |
| Dextrose (Dextrose) |
| Diazepam (Diazepam) |
| Diphenhydramine (Diphenhydramine) |
| Dobutamine (Dobutamine) |
| Dopamine (Dopamine) |
| Drotaverine (Drotaverinum) |
| Imatinib (Imatinib) |
| Imipenem (Imipenem) |
| Immunoglobulin human normal (IgG + IgA + IgM) (Immunoglobulin human normal (IgG + IgA + IgM)) |
| Human normal immunoglobulin (Human normal immunoglobulin) |
| Itraconazole (Itraconazole) |
| Potassium chloride (Potassium chloride) |
| Calcium gluconate (Calcium gluconate) |
| Captopril (Captopril) |
| Caspofungin (Caspofungin) |
| Ketamine |
| Ketoprofen (Ketoprofen) |
| Clotrimazole (Clotrimazole) |
| Colistimethate sodium (Colistimethate sodium) |
| Complex of amino acids for parenteral nutrition |
| Platelet concentrate (CT) |
| Lactulose (Lactulose) |
| Levofloxacin (Levofloxacin) |
| Lidocaine (Lidocaine) |
| Lisinopril (Lisinopril) |
| Linezolid (Linezolid) |
| Magnesium sulfate (Magnesium sulfate) |
| Mannitol (Mannitol) |
| Meropenem (Meropenem) |
| Methylprednisolone (Methylprednisolone) |
| Methyluracil (Dioxomethyltetrahydropyrimidine) (Methyluracil (Dioxomethyltetrahydropyrimidine)) |
| Metronidazole (Metronidazole) |
| Micafungin (Micafungin) |
| Moxifloxacin (Moxifloxacin) |
| Morphine (Morphine) |
| Nadroparin calcium (Nadroparin calcium) |
| Sodium acetate |
| Sodium bicarbonate (Sodium hydrocarbonate) |
| Sodium chloride (Sodium chloride) |
| Naphazoline (Naphazoline) |
| Nilotinib (Nilotinib) |
| Nicergoline (Nicergoline) |
| Norepinephrine (Norepinephrine) |
| Omeprazole (Omeprazole) |
| Ondansetron (Ondansetron) |
| Ofloxacin (Ofloxacin) |
| Pipecuronium bromide (Pipekuroniyu bromide) |
| Piperacillin (Piperacillin) |
| Plasma, fresh frozen |
| Povidone - iodine (Povidone - iodine) |
| Prednisolone (Prednisolone) |
| Procaine (Procaine) |
| Propofol (Propofol) |
| Rivaroxaban (Rivaroxaban) |
| Rocuronium bromide (Rocuronium) |
| Salbutamol (Salbutamol) |
| Smectite dioctahedral (Dioctahedral smectite) |
| Spironolactone (Spironolactone) |
| Sulfadimethoxine (Sulfadimethoxine) |
| Sulfamethoxazole (Sulphamethoxazole) |
| Tazobactam (Tazobactam) |
| Tigecycline (Tigecycline) |
| Ticarcillin (Ticarcillin) |
| Thiopental-sodium (Thiopental sodium) |
| Tobramycin (Tobramycin) |
| Torasemide (Torasemide) |
| Tramadol (Tramadol) |
| Tranexamic acid (Tranexamic acid) |
| Trimecain (Trimecaine) |
| Trimethoprim (Trimethoprim) |
| Famotidine (Famotidine) |
| Famciclovir (Famciclovir) |
| Phenylephrine (Phenylephrine) |
| Phenobarbital (Phenobarbital) |
| Fentanyl (Fentanyl) |
| Filgrastim (Filgrastim) |
| Fluconazole (Fluconazole) |
| Folic acid |
| Furosemide (Furosemide) |
| Chloramphenicol (Chloramphenicol) |
| Chlorhexidine (Chlorhexidine) |
| Chloropyramine (Chloropyramine) |
| Cefepime (Cefepime) |
| Cefoperazone (Cefoperazone) |
| Ciprofloxacin (Ciprofloxacin) |
| Enoxaparin sodium (Enoxaparin sodium) |
| Epinephrine (Epinephrine) |
| Erythromycin (Erythromycin) |
| erythrocyte mass |
| Erythrocyte suspension |
| Ertapenem (Ertapenem) |
Groups of drugs according to ATC used in the treatment
Hospitalization
Indications for hospitalization:
Indications for emergency hospitalization:
infectious complications;
· blast crisis;
hemorrhagic syndrome.
Indications for planned hospitalization:
For verification of the diagnosis and selection of therapy;
administering chemotherapy.
Prevention
Preventive actions: no.
Further management:
Patients with an established diagnosis of CML are under the supervision of a hematologist and they are monitored for the effectiveness of treatment according to indicators (see paragraph 15).
Information
Sources and literature
- Minutes of the meetings of the Expert Council of the RCHD MHSD RK, 2015
- References: 1) Scottish Intercollegiate Guidelines Network (SIGN). SIGN 50: a guideline developer's handbook. Edinburgh: SIGN; 2014. (SIGN publication no. 50). . Available from URL: http://www.sign.ac.uk. 2) Khoroshko N.D., Turkina A.G., Kuznetsov S.V. and others. Chronic myeloid leukemia: advances in modern treatment and prospects // Hematology and transfusiology. - 2001. - No. 4. - C. 3-8. 3) Baccarani M., Pileri S., Steegmann J.-L., Muller M., Soverini S., Dreyling M. Chronic myeloid leukemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology 23 (Supplement 7): vii72–vii77, 2012. 4) Baccarani M., Cortes J., Pane F. et al. Chronic myeloid leukemia: an update of concepts and management recommendations of European Leukemia Net. J Clin Oncol 2009; 27:6041–6051. 5) Vardiman JW, Melo JV, Baccarani M, Thiele J. Chronic myelogenous leukemia, BCR-ABL1 positive. In Swerdlowsh .et al (eds), WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues. Lyon: IARC 2008; 32–37. 6) Turkina A.G., Khoroshko N.D., Druzhkova G.A., Zingerman B.V., Zakharova E.S., Chelysheva E.S., Vinogradova O.Yu., Domracheva E.V., Zakharova A.V., Kovaleva L.G., Koloseinova T.I., Kolosova L.Yu., Zhuravlev V.S., Tikhonova L.Yu. The effectiveness of therapy with matinib mesylate (Glivec) in the chronic phase of myeloid leukemia; 2003. 7) Rüdiger Hehlmann. How do I treat CML blast crisis? July 26, 2012; Blood: 120(4). 8) Moody K, Finlay J, Mancuso C, Charlson M. Feasibility and safety of a pilot randomized trial of infection rate: neutropenic diet versus standard food safety guidelines. J Pediatric Hematol Oncol. 2006 Mar; 28(3):126-33. 9) Gardner A, Mattiuzzi G, Faderl S, Borthakur G, Garcia-Manero G, Pierce S, Brandt M, Estey E. Randomized comparison of cooked and noncooked diets in patients undergoing remission induction therapy for acute myeloid leukemia. J Clin Oncol. 2008 Dec 10; 26(35):5684-8. 10) Carr SE, Halliday V. Investigating the use of the neutropenic diet: a survey of UK dietitians. J Hum Nutr Diet. 2014 Aug 28. 11) Boeckh M. Neutropenic diet-good practice or myth? Biol Blood Marrow Transplant. 2012 Sep; 18(9):1318-9. 12) Trifilio, S., Helenowski, I., Giel, M. et al. Questioning the role of a neutropenic diet following hematopoetic stem cell transplantation. Biol Blood Marrow Transplant. 2012; 18:1387–1392. 13) DeMille, D., Deming, P., Lupinacci, P., and Jacobs, L.A. The effect of the neutropenic diet in the outpatient setting: a pilot study. Oncol Nurs Forum. 2006; 33:337–343. 14) Blood Transfusion Guideline, CB0, 2011 (www.sanquin.nl) 15) Programmed treatment of blood system diseases: A collection of diagnostic algorithms and protocols for the treatment of blood system diseases / ed. V. G. Savchenko. - M.: Practice, 2012. - 1056 p. 16) Szczepiorkowski ZM, Dunbar NM. Transfusion guidelines: when to transfuse. Hematology Am SocHematolEduc Program. 2013; 2013:638-44. 17) Timothy Hughes and Deborah White. Which TKI? An embarrassment of riches for chronic myeloid leukemia patients. ASH Education Book December 6, 2013vol. 2013 no. 1 168-175. 18) NCCN Clinical Practice Guidelines in Oncology, 2014 (http://www.nccn.org). 19) Sokal JE, Cox EB, Baccarani M et al. Prognostic discrimination in ‘good-risk’ chronic granulocytic leukemia. Blood 1984; 63:789–799. 20) Hasford J, Pfirrmann M, Hehlmann R et al. A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa. J Natl Cancer Inst 1998; 90:850–858. 21) Hasford J, Baccarani M, Hoffmann V et al. Predicting complete cytogenetic response and subsequent progression-free survival in 2060 patients with CML on imatinib treatment: the EUTOS score. Blood 2011; 118:686–692.
Information
List of protocol developers with qualification data:
1) Kemaikin Vadim Matveyevich - Candidate of Medical Sciences, JSC "National Scientific Center of Oncology and Transplantation", Head of the Department of Oncohematology and Bone Marrow Transplantation.
2) Klodzinsky Anton Anatolyevich - Candidate of Medical Sciences, JSC "National Scientific Center of Oncology and Transplantation", Hematologist, Department of Oncohematology and Bone Marrow Transplantation.
3) Ramazanova Raigul Mukhambetovna - doctor of medical sciences, professor of JSC "Kazakh Medical University of Continuing Education", head of the course of hematology.
4) Gabbasova Saule Telembaevna - RSE on REM "Kazakh Research Institute of Oncology and Radiology", head of the department of hematological malignancies.
5) Karakulov Roman Karakulovich - Doctor of Medical Sciences, Professor, Academician of the MAI RSE on REM "Kazakh Research Institute of Oncology and Radiology", Chief Researcher of the Department of Hemoblastoses.
6) Tabarov Adlet Berikbolovich - Head of the Innovation Management Department of the RSE on the REM "Hospital of the Medical Center Administration of the President of the Republic of Kazakhstan", clinical pharmacologist, pediatrician.
Indication of no conflict of interest: missing.
Reviewers:
1) Afanasiev Boris Vladimirovich - Doctor of Medical Sciences, Director of the Research Institute of Children's Oncology, Hematology and Transplantation named after R.M. Gorbacheva, Head of the Department of Hematology, Transfusiology and Transplantology of the State Budgetary General Educational Institution of Higher Professional Education of the First St. Petersburg State Medical University. I.P. Pavlova.
2) Rakhimbekova Gulnara Aibekovna - Doctor of Medical Sciences, Professor, JSC "National Scientific Medical Center", Head of Department.
3) Pivovarova Irina Alekseevna - Medicinae Doctor, Master of Business Administration, Chief Freelance Hematologist of the Ministry of Health and Social Development of the Republic of Kazakhstan.
Indication of the conditions for revising the protocol: revision of the protocol after 3 years and / or when new methods of diagnosis and / or treatment with a higher level of evidence appear.
Attached files
Attention!
- By self-medicating, you can cause irreparable harm to your health.
- The information posted on the MedElement website and in the mobile applications "MedElement (MedElement)", "Lekar Pro", "Dariger Pro", "Diseases: Therapist's Handbook" cannot and should not replace an in-person consultation with a doctor. Be sure to contact medical facilities if you have any diseases or symptoms that bother you.
- The choice of drugs and their dosage should be discussed with a specialist. Only a doctor can prescribe the right medicine and its dosage, taking into account the disease and the condition of the patient's body.
- The MedElement website and mobile applications "MedElement (MedElement)", "Lekar Pro", "Dariger Pro", "Diseases: Therapist's Handbook" are exclusively information and reference resources. The information posted on this site should not be used to arbitrarily change the doctor's prescriptions.
- The editors of MedElement are not responsible for any damage to health or material damage resulting from the use of this site.
