Chronic myeloid leukemia how long do they live? How long do they live with chronic myeloid leukemia, and how does the stage of the disease affect life expectancy? Chronic myeloid
![Chronic myeloid leukemia how long do they live? How long do they live with chronic myeloid leukemia, and how does the stage of the disease affect life expectancy? Chronic myeloid](https://i0.wp.com/polismed.com/upfiles/other/images-art-2/mielo/2.jpg)
Chronic myeloid leukemia- tumor blood disease. It is characterized by uncontrolled growth and reproduction of all blood germ cells, while young malignant cells are able to mature into mature forms.
Chronic myeloid leukemia (synonym – chronic myeloid leukemia) – tumor blood disease. Its development is associated with changes in one of the chromosomes and the appearance chimeric (“stitched” from different fragments) gene that disrupts hematopoiesis in the red bone marrow.
During chronic myeloid leukemia, the content of a special type of leukocyte increases in the blood - granulocytes . They are formed in the red bone marrow in huge quantities and enter the bloodstream without having time to fully mature. At the same time, the content of all other types of leukocytes decreases.
Some facts about the prevalence of chronic myeloid leukemia:
- Every fifth tumor blood disease is chronic myeloid leukemia.
- Among all blood tumors, chronic myeloid leukemia ranks 3rd in North America and Europe, and 2nd in Japan.
- Every year, chronic myeloid leukemia occurs in 1 in 100,000 people worldwide.
- Over the past 50 years, the prevalence of the disease has not changed.
- Most often, the disease is detected in people aged 30–40 years.
- Men and women get sick at approximately the same frequency.
Causes of chronic myeloid leukemia
The causes of chromosomal abnormalities leading to chronic myeloid leukemia are still not well understood.The following factors are believed to be relevant:As a result of chromosome breakdowns, a DNA molecule with a new structure appears in red bone marrow cells. A clone of malignant cells is formed, which gradually displace all others and occupy the bulk of the red bone marrow. The vicious gene provides three main effects:
- Cells multiply uncontrollably, like cancer cells.
- Natural death mechanisms stop working for these cells.
Phases of chronic myeloid leukemia
- Chronic phase. The majority of patients who see a doctor are in this phase (about 85%). The average duration is 3 – 4 years (depending on how timely and correctly the treatment is started). This is a stage of relative stability. The patient is concerned about minimal symptoms, which he may not pay attention to. Sometimes doctors detect the chronic phase of myeloid leukemia by chance, during a general blood test.
- Acceleration phase. During this phase, the pathological process is activated. The number of immature white blood cells in the blood begins to increase rapidly. The acceleration phase is, as it were, transitional from chronic to the last, third.
- Terminal phase. The final stage of the disease. Occurs when changes in chromosomes increase. Red bone marrow is almost completely replaced by malignant cells. During the terminal stage, the patient dies.
Manifestations of chronic myeloid leukemia
Symptoms of the chronic phase:
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- Signs associated with impaired platelet and white blood cell function : various bleedings or, on the contrary, the formation of blood clots.
- Signs associated with an increase in platelet count and, as a result, increased blood clotting : circulatory disorders in the brain (headaches, dizziness, decreased memory, attention, etc.), myocardial infarction, blurred vision, shortness of breath.
Acceleration phase symptoms
During the acceleration phase, signs of the chronic stage increase. Sometimes it is at this time that the first signs of the disease appear, which force the patient to visit the doctor for the first time.Symptoms of the terminal stage of chronic myeloid leukemia:
- Sharp weakness , significant deterioration in general health.
- Prolonged aching pain in joints and bones . Sometimes they can be very strong. This is due to the proliferation of malignant tissue in the red bone marrow.
- Heavy sweats .
- Periodic causeless rise in temperature up to 38 - 39⁰C, during which severe chills occur.
- Weight loss .
- Increased bleeding , the appearance of hemorrhages under the skin. These symptoms occur as a result of a decrease in the number of platelets and decreased blood clotting.
- Rapid increase in spleen size : the stomach increases in size, a feeling of heaviness and pain appears. This occurs due to the growth of tumor tissue in the spleen.
Diagnosis of the disease
Which doctor should you contact if you have symptoms of chronic myeloid leukemia?
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A hematologist treats blood diseases of a tumor nature. Many patients initially turn to a general practitioner, who then refers them to a hematologist for consultation.
Examination at the doctor's office
An appointment at a hematologist’s office is carried out as follows:- Questioning the patient . The doctor clarifies the patient’s complaints, clarifies the time of their occurrence, and asks other necessary questions.
- Feeling the lymph nodes : submandibular, cervical, axillary, supraclavicular and subclavian, elbow, inguinal, popliteal.
- Feeling the abdomen to determine the enlargement of the liver and spleen. The liver is felt under the right rib while lying on the back. The spleen is on the left side of the abdomen.
When can a doctor suspect a patient has chronic myeloid leukemia?
Symptoms of chronic myeloid leukemia, especially in the initial stages, are nonspecific - they can occur in many other diseases. Therefore, the doctor cannot assume a diagnosis only on the basis of examination and complaints of the patient. Typically, suspicion arises based on one of two studies:- General blood analysis . It contains an increased number of leukocytes and a large number of their immature forms.
- Ultrasound of the abdomen . An increase in the size of the spleen is detected.
How is a complete examination performed if chronic myeloid leukemia is suspected??
Study title | Description | What does it reveal? |
General blood analysis | A routine clinical examination is performed if any disease is suspected. A general blood test helps determine the total content of leukocytes, their individual varieties, and immature forms. Blood for analysis is taken from a finger or vein in the morning. | The result depends on the phase of the disease. Chronic phase:
|
Puncture and biopsy of red bone marrow | Red bone marrow is the main hematopoietic organ in humans, which is located in the bones. During the examination, a small fragment is obtained using a special needle and sent to the laboratory for examination under a microscope. Carrying out the procedure:
| In the red bone marrow, approximately the same picture is found as in a general blood test: a sharp increase in the number of precursor cells that give rise to leukocytes. |
Cytochemical study | When special dyes are added to blood and red bone marrow samples, certain substances may react with them. This is the basis for a cytochemical study. It helps to establish the activity of certain enzymes and serves to confirm the diagnosis of chronic myeloid leukemia, helping to distinguish it from other types of leukemia. | In chronic myeloid leukemia, a cytochemical study reveals a decrease in the activity of a special enzyme in granulocytes - alkaline phosphatase
. |
Blood chemistry | With chronic myeloid leukemia, the content of certain substances in the blood changes, which is an indirect diagnostic sign. Blood is taken for analysis from a vein on an empty stomach, usually in the morning. | Substances whose content in the blood is increased in chronic myeloid leukemia:
|
Cytogenetic study | During a cytogenetic study, the entire genome (set of chromosomes and genes) of a person is studied. For the study, blood is used, which is taken from a vein into a test tube and sent to the laboratory. The result is usually ready in 20 – 30 days. The laboratory uses special modern tests, during which various parts of the DNA molecule are identified. | In chronic myeloid leukemia, a cytogenetic study reveals a chromosomal disorder, which was called Philadelphia chromosome
. In the cells of patients, chromosome No. 22 is shortened. The lost section is added to chromosome No. 9. In turn, a fragment of chromosome No. 9 joins chromosome No. 22. A kind of exchange occurs, as a result of which genes begin to work incorrectly. The result is myeloid leukemia. Other pathological changes on chromosome No. 22 are also detected. By their nature one can partially judge the prognosis of the disease. |
Ultrasound of the abdominal organs. | Ultrasound is used in patients with myeloid leukemia to detect enlargement of the liver and spleen. Ultrasound helps distinguish leukemia from other diseases. | |
Laboratory indicators
General blood analysis- Leukocytes: significantly increased from 30.0 10 9 /l to 300.0-500.0 10 9 /l
- Leukocyte formula shift to the left: young forms of leukocytes predominate (promyelocytes, myelocytes, metamyelocytes, blast cells)
- Basophils: increased amount 1% or more
- Eosinophils: increased level, more than 5%
- Platelets: normal or increased
- Leukocyte alkaline phosphatase is reduced or absent.
- A genetic blood test reveals an abnormal chromosome (Philadelphia chromosome).
Symptoms
The manifestation of symptoms depends on the phase of the disease.Phase I (chronic)
- Long time without symptoms (from 3 months to 2 years)
- Heaviness in the left hypochondrium (due to an enlarged spleen; the higher the level of leukocytes, the larger its size).
- Weakness
- Decreased performance
- Sweating
- Weight loss
- splenic infarction - acute pain in the left hypochondrium, temperature 37.5 -38.5 °C, sometimes nausea and vomiting, touching the spleen is painful.
- Priapism is a painful, excessively prolonged erection.
These symptoms are harbingers of a serious condition (blast crisis) and appear 6-12 months before its onset.
- The effectiveness of drugs (cytostatics) decreases
- Anemia develops
- The percentage of blast cells in the blood increases
- General condition worsens
- The spleen enlarges
- The symptoms correspond to the clinical picture of acute leukemia ( see Acute lymphocytic leiosis).
How is myeloid leukemia treated?
Goal of treatment reduce the growth of tumor cells and reduce the size of the spleen.Treatment of the disease should be started immediately after the diagnosis is made. The prognosis largely depends on the quality and timeliness of therapy.
Treatment includes various methods: chemotherapy, radiation therapy, removal of the spleen, bone marrow transplant.
Treatment with drugs
Chemotherapy- Classic drugs: Myelosan (Mileran, Busulfan), Hydroxyurea (Hydrea, Litalir), Cytosar, 6-mercaptopurni, alpha-interferon.
- New drugs: Gleevec, Sprycel.
Name | Description |
Hydroxyurea drugs:
| How the drug works: Hydroxyurea is a chemical compound that can inhibit the synthesis of DNA molecules in tumor cells. When can they appoint: For chronic myeloid leukemia, accompanied by a significant increase in the number of leukocytes in the blood. How to prescribe: The drug is released in the form of capsules. The doctor prescribes them to the patient in accordance with the chosen dosage regimen. Possible side effects:
|
Gleevec (imatinib mesylate) | How the drug works: The drug suppresses the growth of tumor cells and enhances the process of their natural death. When can they prescribe:
The drug is available in tablet form. The regimen of use and dosage is chosen by the attending physician. Possible side effects: The side effects of the drug are difficult to assess, since patients who take it usually already have severe disorders in various organs. According to statistics, the drug has to be discontinued due to complications quite rarely:
|
Interferon-alpha | How the drug works: Interferon-alpha increases the body's immune strength and suppresses the growth of cancer cells. When is it prescribed?: Interferon-alpha is usually used for long-term maintenance therapy after the white blood cell count has returned to normal. How to prescribe: The drug is used in the form of injection solutions, administered intramuscularly. Possible side effects: Interferon has a fairly large number of side effects, and this is associated with certain difficulties in its use. With proper prescription of the drug and constant monitoring of the patient’s condition, the risk of unwanted effects can be minimized:
|
Bone marrow transplantation
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Red bone marrow transplantation is the most effective treatment for chronic myeloid leukemia. More than half of transplant patients experience sustained improvement for 5 years or longer.
Most often, recovery occurs when red bone marrow is transplanted into a patient under 50 years of age in the chronic phase of the disease.
Stages of red bone marrow transplantation:
- Finding and preparing a donor. The best donor of red bone marrow stem cells is a close relative of the patient: twin, brother, sister. If there are no close relatives or they are not suitable, they look for a donor. A series of tests are carried out to ensure that the donor material will take root in the patient’s body. Today, developed countries have created large donor banks containing tens of thousands of donor samples. This gives a chance to quickly find suitable stem cells.
- Patient preparation. Typically this stage lasts from a week to 10 days. Radiation therapy and chemotherapy are carried out to destroy as many tumor cells as possible and prevent rejection of donor cells.
- The actual red bone marrow transplant. The procedure is similar to a blood transfusion. A catheter is inserted into the patient's vein, through which stem cells are injected into the blood. They circulate in the bloodstream for some time, and then settle in the bone marrow, take root there and begin to work. To prevent rejection of donor material, the doctor prescribes anti-inflammatory and antiallergic drugs.
- Decreased immunity. Donor red bone marrow cells cannot take root and begin to function immediately. This takes time, usually 2 – 4 weeks. During this period, the patient's immunity is greatly reduced. He is placed in a hospital, completely protected from contact with infections, and prescribed antibiotics and antifungal agents. This period is one of the most difficult. Body temperature rises significantly, chronic infections can be activated in the body.
- Engraftment of donor stem cells. The patient's health begins to improve.
- Recovery. Over several months or years, red bone marrow function continues to recover. Gradually the patient recovers and his ability to work is restored. But he still needs to be under the supervision of a doctor. Sometimes the new immunity cannot cope with some infections, in which case vaccinations are given about a year after the bone marrow transplant.
Radiation therapy
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In what phase of the disease is radiation therapy used?
Radiation therapy is used in the advanced stage of chronic myeloid leukemia, which is characterized by the following symptoms:
- Significant proliferation of tumor tissue in the red bone marrow.
- Growth of tumor cells in tubular bones 2 .
- Severe enlargement of the liver and spleen.
Gamma therapy is used - irradiation of the spleen area with gamma rays. The main task is to destroy or stop the growth of malignant tumor cells. The radiation dose and radiation regimen are determined by the attending physician.
Removal of the spleen (splenectomy)
Removal of the spleen is rarely used for limited indications (splenic infarction, thrombocytopenia, severe abdominal discomfort).The operation is usually performed in the terminal phase of the disease. Together with the spleen, a large number of tumor cells are removed from the body, thereby easing the course of the disease. After surgery, the effectiveness of drug therapy usually increases.
What are the main indications for surgery?
- Splenic rupture.
- Threat of splenic rupture.
- A significant increase in size of the organ, which leads to severe discomfort.
Purification of blood from excess leukocytes (leukapheresis)
With the development of blast crisis, treatment will be the same as for acute leukemia (see acute lymphocytic leukemia).
Leukocytapheresis - a treatment procedure that resembles plasmapheresis (blood purification). A certain amount of blood is taken from the patient and passed through a centrifuge, in which it is purified of tumor cells.
In what phase of the disease is leukocytapheresis performed?
Just like radiation therapy, leukocytapheresis is performed during the advanced stage of myeloid leukemia. It is often used in cases where there is no effect from the use of medications. Sometimes leukocytapheresis complements drug therapy.
Myeloid leukemia or myeloid leukemia is a dangerous cancer of the hematopoietic system that affects bone marrow stem cells. People often refer to leukemia as “bleeding”. As a result, they completely stop performing their functions and begin to rapidly multiply.
In human bone marrow are produced, and. If a patient is diagnosed with myeloid leukemia, then pathologically altered immature cells, which in medicine are called blasts, begin to mature and rapidly multiply in the blood. They completely block the growth of normal and healthy blood cells. After a certain period of time, bone marrow growth stops completely and these pathological cells reach all organs through blood vessels.
In the initial stage of development of myeloid leukemia, there is a significant increase in the number of mature leukocytes in the blood (up to 20,000 per mcg). Gradually their level increases two or more times, and reaches 400,000 mcg. Also, with this disease, there is an increase in the blood level, which indicates a severe course of myeloid leukemia.
Causes
The etiology of acute and chronic myeloid leukemia has not yet been fully studied. But scientists from all over the world are working to solve this problem so that in the future it will be possible to prevent the development of pathology.
Possible causes of the development of acute and chronic myeloid leukemia:
- a pathological change in the structure of a stem cell, which begins to mutate and further create the same ones. In medicine they are called pathological clones. Gradually, these cells begin to enter organs and systems. There is no way to eliminate them using cytostatic drugs;
- exposure to harmful chemicals;
- exposure to ionizing radiation on the human body. In some clinical situations, myeloid leukemia may develop as a consequence of previous radiation therapy for the treatment of another cancer (an effective method for treating tumors);
- long-term use of cytostatic antitumor drugs, as well as some chemotherapeutic agents (usually during the treatment of tumor diseases). Such drugs include Leukeran, Cyclophosphamide, Sarcozolit and others;
- negative effects of aromatic hydrocarbons;
- some viral diseases.
The etiology of the development of acute and chronic myeloid leukemia continues to be studied to this day.
Risk factors
- the effect of radiation on the human body;
- patient's age;
Kinds
Myeloid leukemia in medicine is divided into two types:
- chronic myeloid leukemia (the most common form);
- acute myeloid leukemia.
Acute myeloid leukemia
Acute myeloid leukemia is a blood disease in which uncontrolled proliferation of white blood cells occurs. Full-fledged cells are replaced with leukemic ones. The pathology is fast-acting and without adequate treatment a person may die within a few months. The patient’s life expectancy directly depends on the stage at which the presence of the pathological process is detected. Therefore, it is important, if you have the first symptoms of myeloid leukemia, to contact a qualified specialist who will conduct a diagnosis (the most informative is a blood test), confirm or refute the diagnosis. Acute myeloid leukemia affects people from different age groups, but most often it affects people over 40 years of age.
Acute symptoms
Symptoms of the disease usually appear almost immediately. In very rare clinical situations, the patient's condition worsens gradually.
- nosebleeds;
- hematomas that form over the entire surface of the body (one of the most important symptoms for diagnosing pathology);
- hyperplastic gingivitis;
- night sweats;
- ossalgia;
- shortness of breath appears even with minor physical exertion;
- a person often falls ill with infectious diseases;
- the skin is pale, which indicates a disorder of hematopoiesis (this symptom is one of the first to appear);
- the patient's body weight gradually decreases;
- petechial rashes are localized on the skin;
- temperature rise to subfebrile level.
If you have one or more of these symptoms, it is recommended to visit a medical facility as soon as possible. It is important to remember that the prognosis of the disease, as well as the life expectancy of the patient in whom it is detected, largely depends on timely diagnosis and treatment.
Chronic myeloid leukemia
Chronic myeloid leukemia is a malignant disease that exclusively affects hematopoietic stem cells. Gene mutations occur in immature myeloid cells, which in turn produce red blood cells, platelets, and virtually all types of white blood cells. As a result, an abnormal gene called BCR-ABL is formed in the body, which is extremely dangerous. It “attacks” healthy blood cells and converts them into leukemia cells. Their location is the bone marrow. From there, they spread through the bloodstream throughout the body and affect vital organs. Chronic myeloid leukemia does not develop rapidly; it is characterized by a long and measured course. But the main danger is that without proper treatment it can develop into acute myeloid leukemia, which can kill a person in a few months.
The disease in most clinical situations affects people from various age groups. In children, it occurs sporadically (cases of morbidity are very rare).
Chronic myeloid leukemia occurs in several stages:
- chronic. Leukocytosis increases gradually (it can be detected using a blood test). Along with it, the level of granulocytes and platelets increases. Splenomegaly also develops. At first, the disease may be asymptomatic. Later, the patient develops rapid fatigue, sweating, and a feeling of heaviness under the left rib, caused by an enlarged spleen. As a rule, a patient turns to a specialist only after he experiences shortness of breath during minor exertion or heaviness in the epigastrium after eating. If you conduct an X-ray examination at this moment, the image will clearly show that the dome of the diaphragm is lifted upward, the left lung is pushed back and partially compressed, and the stomach is also compressed due to the enormous size of the spleen. The most terrible complication of this condition is splenic infarction. Symptoms: pain on the left under the rib, radiating to the back, fever, general intoxication of the body. At this time, the spleen is very painful on palpation. Blood viscosity increases, which causes veno-occlusive liver damage;
- acceleration stage. At this stage, chronic myeloid leukemia practically does not manifest itself or its symptoms are expressed to an insignificant extent. The patient's condition is stable; sometimes there is an increase in body temperature. A person gets tired quickly. The level of leukocytes increases, and also increases. If you conduct a thorough blood test, you will find blast cells and promyelocytes in it, which should not normally be present. The level of basophils increases up to 30%. As soon as this happens, patients begin to complain of skin itching and a feeling of heat. All this is due to an increase in the amount of histamine. After additional tests have been performed (the results of which are placed in the medical history to observe trends), the dose of the chemical is increased. a drug used to treat myeloid leukemia;
- terminal stage. This stage of the disease begins with the appearance of joint pain, severe weakness and an increase in temperature to high numbers (39–40 degrees). The patient's weight decreases. A characteristic symptom for this stage is splenic infarction due to its excessive enlargement. The man is in very serious condition. He develops hemorrhagic syndrome and blast crisis. More than 50% of people are diagnosed with bone marrow fibrosis at this stage. Additional symptoms: enlarged peripheral lymph nodes (detected by a blood test), normochromic anemia, the central nervous system is affected (paresis, nerve infiltration). The patient's life expectancy depends entirely on supportive drug therapy.
Diagnostics
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Additional techniques:
Treatment
When choosing a specific treatment method for a given disease, it is necessary to take into account the stage of its development. If the disease is detected at an early stage, the patient is usually prescribed tonic drugs and a balanced diet rich in vitamins.
The main and most effective method of treatment is drug therapy. For treatment, cytostatics are used, the action of which is aimed at stopping the growth of tumor cells. Radiation therapy, bone marrow transplantation and blood transfusions are also actively used.
Most treatments for this disease cause quite severe side effects:
- inflammation of the gastrointestinal mucosa;
- constant nausea and vomiting;
- hair loss.
To treat the disease and prolong the patient’s life, the following chemotherapy drugs are used:
- "Myelobromol";
- "Allopurine";
- "Myelosan".
The choice of medications directly depends on the stage of the disease, as well as on the individual characteristics of the patient. All medications are prescribed strictly by the attending physician! Adjusting the dose yourself is strictly prohibited!
Only a bone marrow transplant can lead to a complete recovery. But in this case, the stem cells of the patient and the donor must be 100% identical.
RCHR (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 advice
RSE at the RVC "Republican Center"
healthcare development"
Ministry of Health
and social development
Republic of Kazakhstan
dated July 9, 2015
Protocol No. 6
Protocol name: Chronic myeloid leukemia
Chronic myeloid leukemia (CML)- a 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 22, the BCR-ABL fusion gene is formed on it.
Protocol code:
ICD-10 code: C92.1 - chronic myeloid leukemia
Date of development of the protocol: 2015
Abbreviations used in the protocol:
* - drugs purchased as part of a one-time import
HIV - human immunodeficiency virus
TKIs - tyrosine kinase inhibitors
ELISA - enzyme immunoassay
OAM - general urine analysis
CBC - complete blood count
BMT - hematopoietic stem cell/bone marrow transplantation
CML - chronic myeloid leukemia
ECG - electrocardiogram
Ultrasound - ultrasound examination
BCR - ABL - breakpoint cluster region-Abelson
CCA - Complex chromosomal aberrations
ELN - European Leukemia Net
FISH - 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 for the recommendations |
A | A high-quality meta-analysis, 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. |
IN | High-quality (++) systematic review of cohort or case-control studies or High-quality (++) cohort or case-control studies with very low risk of bias or RCTs with low (+) risk of bias, the results of which can be generalized to an appropriate population. |
WITH | A cohort or case-control study or a controlled trial without randomization with a low risk of bias (+), the results of which can be generalized to an appropriate population, or an RCT with a very low or low risk of bias (++ or +), the results of which are not can be directly generalized to the relevant population. |
D | Case series description or |
Uncontrolled study or | |
Expert opinion |
Classification
Clinical classification:
During CML, there are 3 phases: chronic, transitional (acceleration phase) and terminal phase (blast transformation or blast crisis). The criteria for the acceleration and blast crisis phases 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 therapy | Not applicable | Not applicable | Not applicable |
Leukocytes | an increase in the number of leukocytes (>10x109l) in the blood despite 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 liver and spleen, including lymph nodes, skin, central nervous system, bones and lungs.Clinical picture
Symptoms, course
Diagnostic criteria for making a diagnosis
:
· presence of the Philadelphia chromosome (balanced translocation t(9;22) (q34; q11) according to a standard cytogenetic study of 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;
· low-grade fever;
· chilling;
pain in bones or joints;
· weight loss;
· hemorrhagic rashes in the form of petechiae and ecchymoses on the skin;
· epistaxis;
· menorrhagia;
· increased bleeding;
· enlarged lymph nodes;
· pain and heaviness in the left upper abdomen (enlarged spleen);
· heaviness in the right hypochondrium.
Anamnesis:
you should pay attention to:
· long-term weakness;
· rapid fatigue;
· frequent infectious diseases;
· increased bleeding;
· appearance of hemorrhagic rashes on the skin and mucous membranes;
· enlarged liver, spleen.
Physical examination:
· pallor of the skin;
· hemorrhagic rashes - petechiae, ecchymoses;
shortness of breath;
· tachycardia;
liver enlargement;
· enlarged spleen;
· enlarged 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 molecular genetic methods - FISH or polymerase chain reaction (detection of the chimeric gene BCR-ABL)
Diagnostics
List of basic and additional diagnostic measures:
Basic (mandatory) diagnostic examinations performed on an outpatient basis:
· UAC;
· myelogram;
· biochemical blood test (uric acid);
X-ray of the chest organs.
Additional diagnostic examinations performed on an outpatient basis:
· bone marrow examination using FISH method (t(9;22)/BCR/ABL);
· ELISA for HIV markers;
· ELISA for markers of herpes group viruses;
· Rehberg-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 for 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.
Basic (mandatory) diagnostic examinations carried out at the hospital level:
· CBC with platelet and reticulocyte counting;
· biochemical blood test (total protein, albumin, globulins, IgA, IgM, IgG levels, 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 examination of bone marrow;
· bone marrow examination using FISH method (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 using a flow cytofluorimeter (acute leukemia panel);
· histological examination of biopsy material (lymph node, iliac crest);
· PCR for viral infections (viral hepatitis, cytomegalovirus, herpes simplex virus, Epstein-Barr virus, Varicella/Zoster virus);
X-ray of the paranasal sinuses;
· radiography of bones and joints;
· FGDS;
· Doppler ultrasound of vessels;
· bronchoscopy;
· colonoscopy;
daily blood pressure monitoring;
· 24-hour ECG monitoring;
· spirography.
Diagnostic measures carried out at the stage of emergency medical care:
· collection of complaints and medical history;
· physical examination.
Instrumental studies:
· Ultrasound of the abdominal organs, lymph nodes: increased size of the liver, spleen, peripheral lymphadenopathy.
· CT scan of the thoracic segment: to exclude infiltration of lung tissue.
· ECG: Impaired conduction of impulses in the heart muscle.
· EchoCG: to exclude in patients heart defects, arrhythmias and other diseases accompanied by damage to the parts of the heart.
· FGDS: leukemic infiltration of the mucous membrane of the gastrointestinal tract, which can cause ulcerative lesions of the stomach, duodenum, and gastrointestinal bleeding.
· Bronchoscopy: detection of the source of bleeding.
Indications for consultation with 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;
Dermatovenerologist - skin syndrome
· infectious disease specialist - suspicion of viral infections;
· cardiologist - uncontrolled hypertension, chronic heart failure, heart rhythm and conduction disorders;
· neurologist 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 - psychosis;
· psychologist - depression, anorexia, etc.;
· resuscitator - treatment of severe sepsis, septic shock, acute pulmonary injury syndrome with differentiation syndrome and terminal conditions, 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 antiglobulin test, ineffective transfusions, 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 dentofacial system.
Laboratory diagnostics
Laboratory research:
· General blood analysis: leukocytes, erythrocytes and platelets are counted. Characterized by absolute neutrophilic leukocytosis with a shift of the nuclear formula to the left (to promyelocytes or blasts), absence of leukemic failure, basophilic-eosinophilic association. At the onset of the disease, the hemoglobin level may be within normal limits or elevated, and moderate thrombocytosis may be observed. In the acceleration phase and blast crisis, thrombocytopenia and anemia may develop.
· Blood chemistry: there is an increase in LDH activity, hyperuricemia.
· Morphological study: bone marrow aspirate shows hypercellular bone marrow, increased number of blasts, basophils and eosinophils.
· Immunophenotyping: is carried out to determine the immunophenotype of blasts when they are in 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 in a cytogenetic study.
Differential diagnosis can be carried out with leukemoid reaction of the myeloid type, which occurs in various infections (sepsis, tuberculosis) and some tumors (Hodgkin lymphoma, solid tumors), as well as other chronic myeloproliferative diseases. The main diagnostic criteria for chronic myeloid leukemia are:
- the presence of anemia that is not characteristic of the 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 in the case of 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 steadily progress).
- the presence in chronic myelosis of intermediate forms between “powerful” elements and mature granulocytes, while acute leukemia is characterized by “leukemic gaping”;
- the presence of an eosinophilic-basophilic association, which is absent in acute leukemia;
- hyperthrombocytosis, sometimes observed in chronic myelosis, whereas in acute leukemia there is thrombocytopenia from the very beginning.
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Treatment
Treatment goals:
· obtaining hematological remission, cytogenetic and molecular response.
Treatment tactics:
Non-drug treatment.
Mode: general security.
Diet: neutropenic patients are not recommended to follow a certain diet ( level of evidence B).
Transfusion support
Prophylactic transfusions of apheresis virus-inactivated, preferably irradiated platelets are carried out when thrombocytopenia is less than 10x109 / L or at a level less than 20x109 / L in the presence 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.
Transfusion of leukofiltered, preferably irradiated, red blood cells is carried out in the presence of poor tolerability 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, concomitant diseases, tolerability of chemotherapy and the development of complications in the previous stages of treatment.
Laboratory indicators for determining indications are of auxiliary value, mainly for assessing the need for prophylactic transfusions of platelet concentrate.
Indications for transfusions also depend on the time after a course of chemotherapy - the predicted decrease in indicators in the next few days is taken into account.
Red blood cell mass/suspension (level of evidence)D):
· 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 cell-containing media for chronic anemia - symptomatic anemia (manifested by tachycardia, shortness of breath, angina pectoris, syncope, denovo depression or ST elevation);
· A hemoglobin level of less than 30 g/l is an absolute indication for red blood cell transfusion;
· In the absence of decompensated diseases of the cardiovascular system and lungs, hemoglobin levels may be indications for prophylactic red blood cell transfusion in chronic anemia:
Platelet concentrate (level of evidence)D):
· If the platelet level decreases to less than 10 x 10 9 / l, apheresis platelet transfusion is performed in order to maintain their level not lower than 30-50 x 10 9 / l, especially in the first 10 days of the course.
· If there is a high risk of hemorrhagic complications (age over 60 years, increase in creatinine level 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 evidence)D):
· FFP transfusions are performed in patients with bleeding or before invasive interventions;
· Patients with an INR of ³2.0 (for neurosurgical interventions ³1.5) are considered candidates for FFP transfusion when planning invasive procedures.
Drug treatment:
During the examination, until the results of a cytogenetic study are received confirming the presence of the Ph+ chromosome in the bone marrow cells, the patient is prescribed hydroxyurea. The dose of the drug is determined taking into account the number of leukocytes and the patient’s weight. For leukocytosis of more than 100 x10 9 /l, hydrea is prescribed at a dose of 50 mcg/kg daily. Subsequently, when the number of leukocytes in the blood decreases, the dose of hydrea is reduced: for leukocytosis 40-100 x 10 9 /l, 40 mg/kg is prescribed, for 20-40 x 10 9 /l - 30 mg/kg, for 5 - 20 x 10 9 / l - 20 mg/kg daily.
Imatinib can be started at any white blood cell count. Imatinib is prescribed (in the chronic phase) at a dose of 400 mg/day orally after meals.
To obtain stable results, taking imatinib must be constant and long-term. Doses of imatinib are adjusted depending on 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 | TOXICITY DEGREE | ||||
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 is normal | 50-74,9 | 25,0-49,0 | Less than 25 |
Hemoglobin | Norm | 100 is normal | 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. Treatment breaks should be taken if severe grade 3 hematological toxicity develops.
Treatment is resumed when clinical and hematological parameters are restored (neutrophils >1.5 thousand/μl, platelets >75 thousand/μl). After relief of toxicity, imatinib is resumed at a dose of 400 mg if the break in treatment is less than 2 weeks. With repeated episodes of cytopenia or their duration lasting more than 2 weeks, the dose of imatinib may be reduced to 300 mg/day. Further reduction in the dose of imatinib is not advisable because it is not possible to achieve its therapeutic concentration in the blood. Therefore, with repeated episodes of cytopenia, breaks in imatinib treatment are taken. When clinical and hematological parameters stabilize within 1-3 months, it is necessary to consider resuming the drug at a dose of 400 mg/day.
Patients who have previously received long-term busulfan, it is recommended to continue taking busulfan(switching to imatinib therapy is ineffective due to the possibility of developing myelosuppression).
Treatment tactics for patients in case of intolerance to imatinib or insufficient response to therapy, as well as in the acceleration phase and blast crisis are presented in Table 2, response criteria in Tables 4 and 5.
Chronic phase | ||
1st line | All patients | Imatinib4 400 mg daily |
2nd line (after imatinib) |
Toxicity, intolerance | Dasatinib or Nilotinib |
Suboptimal response | Continue imatinib at same or higher doses, dasatinib, or nilotinib | |
No response |
Dasatinib or nilotinib Allo-HSCT when progressing to accelerated or blast crisis and in the presence of the T315I mutation |
|
3rd line | Suboptimal response to dasatinib or nilotinib | Continue Dasatinib or Nilotinib. In case of previous resistance to imatinib, the presence of mutations in patients with EBMT scores≤2, consider the possibility of alloBMT |
Failure to respond to Dasatinib or Nilotinib | alloBMT | |
Acceleration and blast crisis phase | ||
1st line of therapy | Patients who did not receive TKIs | Imatinib 600 mg or 800 mg or dasatinib 140 mg or nilotinib 400 mg x 2 times a day followed by alloBMT |
2nd line of therapy | Patients who have previously received imatinib | AlloBMT, nilotinib or dasatinib therapy |
4 For high-risk patients in the chronic phase of CML, it is possible to use nilotinib and dasatinib in the first line of therapy (with a score of >1.2 according to Socal et al, >1480 according to EURO, >87 according to EUTOS - calculator for calculating points 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.
Drug treatment provided on an outpatient basis:
− list of essential medicines indicating the release form (having a 100% probability of use):
Antineoplastic and immunosuppressive drugs
− imatinib 100 mg, capsules;
− nilotinib 200 mg, capsules;
− dasatinib* 70 mg, tablets;
− hydroxyurea 500 mg, capsules;
− allopurinol 100 mg, tablets.
Medicines that weaken the toxic effect of anticancer drugs
· filgrastim, solution for injection 0.3 mg/ml, 1 ml;
· ondansetron, solution for injection 8 mg/4ml.
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, tablet 250 mg.
· 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, 500 mg.
· sulfamethoxazole/trimethoprim, tablet 480 mg.
Solutions used to correct disturbances in water, electrolyte and acid-base balance
· dextrose, solution for infusion 5% 250ml;
· sodium chloride, solution for infusion 0.9% 500ml.
· heparin, solution for injection 5000 IU/ml, 5 ml; (for flushing the catheter)
· rivaroxaban, tablet.
tranexamic acid, capsule/tablet 250 mg;
· ambroxol, solution for oral administration and inhalation, 15 mg/2 ml, 100 ml;
· atenolol, tablet 25 mg;
· acetylsalicylic acid, 50 mg, 100 mg, tablets
· drotaverine, tablet 40 mg;
lactulose, syrup 667 g/l, 500 ml;
Lisinopril, 5 mg tablet;
· methylprednisolone, tablet, 16 mg;
· omeprazole, capsule 20 mg;
Prednisolone, tablet, 5 mg;
· torasemide, tablet 10 mg;
· fentanyl, therapeutic transdermal system 75 mcg/h; (for the treatment of chronic pain in cancer patients)
· chlorhexidine, solution 0.05% 100ml;
Drug treatment provided at the inpatient level:
− list of essential medicines indicating the release form (having a 100% probability of use):
· imatinib 100 mg, capsules;
· nilotinib 200 mg, capsules;
· dasatinib* 70 mg, tablets;
· Hydroxyurea 500 mg, capsules.
− list of additional medicines indicating the release form (less than 100% probability of use):
Medicines that weaken the toxic effect of anticancer drugs:
. filgrastim, solution for injection 0.3 mg/ml, 1 ml;
. ondansetron, solution for injection 8 mg/4ml;
. allopurinol 100 mg, tablets.
Antibacterial agents:
Azithromycin, tablet/capsule, 500 mg; lyophilized powder for the preparation of 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 preparing a solution for intravenous and intramuscular administration 1000 mg+500 mg;
· vancomycin, powder/lyophilisate for solution for infusion 1000 mg;
· gentamicin, solution for injection 80 mg/2 ml 2 ml;
· imipinem, cilastatin powder for solution for infusion, 500 mg/500 mg;
· sodium colistimethate*, lyophilisate for the preparation of solution for infusion, 1 million units/bottle;
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% 100 ml, dental gel 20 g;
· 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/bottle;
Ticarcillin/clavulanic acid, lyophilized powder for the preparation of solution for infusion 3000 mg/200 mg;
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, 500 mg tablet;
· erythromycin, tablet 250 mg;
Ertapenem lyophilisate, for the preparation of a solution for intravenous and intramuscular injections 1 g.
Antifungal drugs
· 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/bottle, tablet 50 mg;
· itraconazole, oral solution 10 mg/ml 150.0;
· caspofungin, lyophilisate for the preparation of solution for infusion 50 mg;
· clotrimazole, cream for external use 1% 30g, 15ml;
· micafungin, lyophilized powder for the preparation of 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;
· acyclovir, powder for solution for infusion, 250 mg;
· acyclovir, cream for external use, 5% - 5.0;
· valacyclovir, tablet, 500 mg;
· valganciclovir, tablet, 450 mg;
· ganciclovir*, lyophilisate for solution for infusion 500 mg;
Famciclovir, tablets, 500 mg No. 14.
Medicines used for pneumocystosis
· sulfamethoxazole/trimethoprim, concentrate for solution for infusion (80mg+16mg)/ml, 5 ml, 480 mg tablet.
Additional immunosuppressive drugs:
· dexamethasone, solution for injection 4 mg/ml 1 ml;
· methylprednisolone, tablet, 16 mg, solution for injection, 250 mg;
· prednisolone, solution for injection 30 mg/ml 1 ml, tablet 5 mg.
Solutions used to correct disturbances of water, electrolyte and acid-base balance, parenteral nutrition
· albumin, solution for infusion 10%, 100 ml, 20% 100 ml;
· water for injection, solution for injection 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 injection 10%, 5 ml;
· calcium chloride, solution for injection 10% 5ml;
· magnesium sulfate, solution for injection 25% 5 ml;
· mannitol, solution for injection 15% -200.0;
· sodium chloride, solution for infusion 0.9% 500ml, 250ml;
· sodium chloride, potassium chloride, sodium acetate solution for infusion in a bottle of 200 ml, 400 ml, 200 ml;
· sodium chloride, potassium chloride, sodium acetate solution for infusion 400ml;
· sodium chloride, potassium chloride, sodium bicarbonate solution for infusion 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 emulsion mixture for inf.: three-chamber containers 2 l;
· hydroxyethyl starch (pentastarch), solution for infusion 6% 500 ml;
· amino acid complex, emulsion for infusion containing a mixture of olive and soybean oils in a ratio of 80:20, a solution of amino acids with electrolytes, a dextrose solution, with a total calorie content of 1800 kcal 1,500 ml three-section container.
Medicines used for intensive care (cardiotonic drugs for the treatment of septic shock, muscle relaxants, vasopressors and anesthetics):
· aminophylline, solution for injection 2.4%, 5 ml;
· amiodarone, solution for injection, 150 mg/3 ml;
· atenolol, tablet 25 mg;
· atracurium besylate, solution for injection, 25 mg/2.5 ml;
· atropine, solution for injection, 1 mg/ml;
· diazepam, solution for intramuscular and intravenous use 5 mg/ml 2 ml;
· dobutamine*, solution for injection 250 mg/50.0 ml;
· dopamine, solution/concentrate for the preparation of solution for injection 4%, 5 ml;
· simple insulin;
· ketamine, solution for injection 500 mg/10 ml;
· morphine, solution for injection 1% 1 ml;
· norepinephrine*, solution for 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 the preparation of solution for intravenous administration 500 mg;
· phenylephrine, solution for injection 1% 1ml;
· phenobarbital, tablet 100 mg;
human normal immunoglobulin, solution for infusion;
· epinephrine, solution for injection 0.18% 1 ml.
Medicines affecting the blood coagulation system
· aminocaproic acid, solution 5% -100 ml;
. anti-inhibitor coagulant complex, lyophilized powder for the preparation of injection solution, 500 IU;
. acetylsalicylic acid, 50 mg, 100 mg, tablets
· heparin, solution for injection 5000 IU/ml, 5 ml;
· hemostatic sponge, size 7*5*1, 8*3;
· nadroparin, solution for injection in pre-filled syringes, 2850 IU anti-Xa/0.3 ml, 5700 IU anti-Xa/0.6 ml;
· enoxaparin, solution for injection in syringes 4000 anti-Xa IU/0.4 ml, 8000 anti-Xa IU/0.8 ml.
Other medicines
· bupivacaine, solution for injection 5 mg/ml, 4 ml;
· lidocaine, solution for injection, 2%, 2 ml;
· procaine, solution for injection 0.5%, 10 ml;
· human immunoglobulin normal solution for intravenous administration 50 mg/ml - 50 ml;
· omeprazole, capsule 20 mg, lyophilized powder for the preparation of solution for injection 40 mg;
· famotidine, lyophilized powder for the preparation of 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, tablet/capsule 5 mg;
· acetylcysteine, powder for solution for oral administration, 3 g;
· heparin, gel in tube 100,000 units 50 g;
· dexamethasone, eye drops 0.1% 8 ml;
Diphenhydramine, solution for injection 1% 1 ml;
· drotaverine, solution for injection 2%, 2 ml;
· captopril, tablet 50 mg;
· ketoprofen, solution for injection 100 mg/2ml;
lactulose, syrup 667 g/l, 500 ml;
· chloramphenicol, sulfadimethoxin, methyluracil, trimecaine ointment for external use 40g;
Lisinopril, 5 mg tablet;
· methyluracil, ointment for topical use in a tube 10% 25g;
· naphazoline, nasal drops 0.1% 10ml;
· nicergoline, lyophilisate for the preparation of injection solution 4 mg;
· povidone-iodine, solution for external use 1 l;
· salbutamol, solution for nebulizer 5 mg/ml-20 ml;
· dioctahedral smectite, powder for preparation of suspension for oral administration 3.0 g;
· spironolactone, capsule 100 mg;
· tobramycin, eye drops 0.3% 5ml;
· torasemide, tablet 10 mg;
· tramadol, solution for injection 100 mg/2ml;
tramadol, capsule 50 mg, 100 mg;
· fentanyl, therapeutic transdermal 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, solution for injection 20 mg/ml 1 ml.
Drug treatment provided at the emergency stage: is not carried out.
Other types of treatment:
Other types of treatment provided on an outpatient basis: do not apply.
Other types of treatment provided at the inpatient level:
Hematopoietic stem cell transplantation.
Allogeneic hematopoietic stem cell transplantation can lead to a cure for patients with CML. However, this type of treatment is applicable to few patients with CML, given the high risk of complications and mortality.
When making a diagnosis and during the treatment of 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 should be calculated before initiating therapy.
Prognostic scores for patients with CML:
Socal et al. | EURO | EUTOS [21 ] | |
Age (years) | 0.116 (age-43.4) | 0.666 if over 50 | Not used |
Dimensions of the spleen (cm) by palpation below the costal arch | 0.345 x (spleen-7.51) | 0.042 x size spleen | 4 x size spleen |
Platelets (x10 9 /l) | 0.188 x [(platelet/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 amount | Amount x 1000 | Sum |
Short | <0,8 | ≤780 | ≤87 |
Intermediate | 0,8-1,2 | 781-1480 | Not used |
High | >1,2 | >1480 | >87 |
Prognostic scale for the probability of response to 2nd generation TKI drugs according to Hammersmith
Other types of treatment provided during emergency medical care: do not apply.
Surgical intervention:
Surgical intervention provided on an outpatient basis: is not carried out.
Surgical intervention provided in an inpatient setting:
With the development of infectious complications and life-threatening bleeding, patients may undergo surgical interventions for emergency indications.
Indicators of treatment effectiveness
Treatment response criteria 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 No |
No metaphases with Ph 1-35% Ph+ metaphases 36-65% Ph+ metaphases 66-95% Ph+ metaphases >95% Ph+ metaphases |
At diagnosis, after 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 cases of treatment failure (primary or secondary resistance) and in cases of unexplained anemia, thrombocytopenia and leukopenia. |
Molecular Full (CMR) Large (MMR) |
BCR-ABL mRNA transcript is not detected by quantitative RT-PCR and/or nested PCR in two blood samples with adequate quality (sensitivity > 104) BCR-ABL to ABL ratio≤0.1% on the international scale |
RT-Q-PCR: every 3 months until MMR is reached, then at least once every 6 months Mutation analysis: performed in case of suboptimal response or treatment failure, always before changing to another TKI |
Determination of optimal, suboptimal responses, and 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 CCA/Ph+ |
3 months | CHR, at least minor cytogenetic response | No cytogenetic response | Less than CHR | - |
6 months | Not less than PCgR | Less PCgR | No CgR | - |
12 months | CCgR | PCgR | Less PCgR | Less than MMR |
18 months | MMR | Less than MMR | Less CCgR | - |
Any time during therapy | Stable or increasing MMR | Loss of MMR, mutations | Loss of CHR, loss of CCgR, mutations, CCA/Ph+ |
Increased transcript levels CCA/Ph+ |
Table 6. Determination of treatment response to second-generation TKIs as second-line therapy in patients with imatinib resistance.
Drugs (active ingredients) used in treatment
Hemostatic sponge |
Azithromycin |
Allopurinol |
Albumin human |
Ambroxol |
Amikacin |
Aminocaproic acid |
Aminoacids for parenteral nutrition+Other medicines (Fat emulsions + Dextrose + Multimineral) |
Aminophylline |
Amiodarone |
Amlodipine |
Amoxicillin |
Amphotericin B |
Anidulafungin |
Antiinhibitory coagulant complex |
Atenolol |
Atracurium besylate |
Acetylsalicylic acid |
Acetylcysteine |
Acyclovir |
Bupivacaine |
Valacyclovir |
Valganciclovir |
Vancomycin |
Water for Injection |
Voriconazole |
Ganciclovir |
Gentamicin |
Heparin sodium |
Hydroxycarbamide |
Hydroxyethyl starch |
Dasatinib |
Dexamethasone |
Dextrose |
Diazepam |
Diphenhydramine |
Dobutamine |
Dopamine |
Drotaverine (Drotaverinum) |
Imatinib |
Imipenem |
Human immunoglobulin normal (IgG+IgA+IgM) (Immunoglobulin human normal (IgG+IgA+IgM)) |
Human normal immunoglobulin |
Itraconazole |
Potassium chloride (Potassium chloride) |
Calcium gluconate |
Captopril |
Caspofungin |
Ketamine |
Ketoprofen |
Clotrimazole |
Colistimethate sodium |
Complex of amino acids for parenteral nutrition |
Platelet concentrate (CT) |
Lactulose |
Levofloxacin |
Lidocaine |
Lisinopril |
Linezolid |
Magnesium sulfate |
Mannitol |
Meropenem |
Methylprednisolone |
Methyluracil (Dioxomethyltetrahydropyrimidine) |
Metronidazole |
Micafungin |
Moxifloxacin |
Morphine |
Nadroparin calcium |
Sodium acetate |
Sodium hydrocarbonate |
Sodium chloride |
Naphazoline |
Nilotinib |
Nicergoline |
Norepinephrine |
Omeprazole |
Ondansetron |
Ofloxacin |
Pipecuronium bromide |
Piperacillin |
Fresh frozen plasma |
Povidone - iodine |
Prednisolone |
Procaine |
Propofol |
Rivaroxaban |
Rocuronium bromide |
Salbutamol |
Dioctahedral smectite |
Spironolactone |
Sulfadimethoxine |
Sulfamethoxazole |
Tazobactam |
Tigecycline |
Ticarcillin |
Thiopental sodium |
Tobramycin |
Torasemide |
Tramadol |
Tranexamic acid |
Trimecaine |
Trimethoprim |
Famotidine |
Famciclovir |
Phenylephrine |
Phenobarbital |
Fentanyl |
Filgrastim |
Fluconazole |
Folic acid |
Furosemide |
Chloramphenicol |
Chlorhexidine |
Chloropyramine |
Cefepime |
Cefoperazone |
Ciprofloxacin |
Enoxaparin sodium |
Epinephrine |
Erythromycin |
Red blood cell mass |
Erythrocyte suspension |
Ertapenem |
Groups of drugs according to ATC used in treatment
Hospitalization
Indications for hospitalization:
Indications for emergency hospitalization:
· infectious complications;
· blast crisis;
· hemorrhagic syndrome.
Indications for planned hospitalization:
· to verify the diagnosis and select therapy;
· Carrying out chemotherapy.
Prevention
Preventive actions: No.
Further management:
Patients with an established diagnosis of CML are under the supervision of a hematologist and are monitored for the effectiveness of treatment according to indicators (see paragraph 15).
Information
Sources and literature
- Minutes of meetings of the Expert Council of the RCHR of the Ministry of Health of the Republic of Kazakhstan, 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: successes of modern treatment and prospects // Hematology and transfusiology. - 2001. - No. 4. - pp. 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., Kolosheinova T.I., Kolosova L.Yu., Zhuravlev V.S., Tikhonova L.Yu. The effectiveness of therapy with matinib mesylate (Gleevec) in the chronic phase of myeloid leukemia; 2003. 7) Rüdiger Hehlmann. How 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 Pediatr Hematol Oncol. Mar 2006; 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, СВ0, 2011 (www.sanquin.nl) 15) Program treatment of diseases of the blood system: Collection of diagnostic algorithms and protocols for the treatment of diseases of the blood system / ed. V. G. Savchenko. - M.: Praktika, 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 details:
1) Kemaykin Vadim Matveevich - Candidate of Medical Sciences, JSC National Scientific Center of Oncology and Transplantology, Head of the Department of Oncohematology and Bone Marrow Transplantation.
2) Anton Anatolyevich Klodzinsky - Candidate of Medical Sciences, JSC National Scientific Center of Oncology and Transplantology, hematologist at the 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 hematology course.
4) Gabbasova Saule Telembaevna - RSE at the RSE "Kazakh Research Institute of Oncology and Radiology", head of the department of hemoblastosis.
5) Karakulov Roman Karakulovich - Doctor of Medical Sciences, Professor, Academician of the MAI RSE at the Kazakh Research Institute of Oncology and Radiology, chief researcher of the department of hemoblastosis.
6) Tabarov Adlet Berikbolovich - Head of the Department of Innovative Management of the RSE at the RSE "Hospital of the Medical Center Administration of the President of the Republic of Kazakhstan", clinical pharmacologist, pediatrician.
Disclosure of no conflict of interest: absent.
Reviewers:
1) Afanasyev Boris Vladimirovich - Doctor of Medical Sciences, Director of the Research Institute of Children's Oncology, Hematology and Transplantology named after R.M. Gorbacheva, Head of the Department of Hematology, Transfusiology and Transplantology, State Budgetary Institution of Higher Professional Education, First St. Petersburg State Medical University named after. I.P. Pavlova.
2) Rakhimbekova Gulnara Aibekovna - Doctor of Medical Sciences, Professor, JSC National Scientific Medical Center, head of the 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 reviewing the protocol: revision of the protocol after 3 years and/or when new diagnostic and/or treatment methods with a higher level of evidence become available.
Attached files
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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.
The content of the article
Chronic myeloid leukemia- a tumor whose cellular substrate consists of granulocytes, mainly neutrophils. Chronic myeloid leukemia develops in people of any age, most often between the ages of 20-50 years; men and women are affected with the same frequency.Etiology and pathogenesis of chronic myeloid leukemia
The influence of ionizing radiation and chemical agents on the development of chronic myeloid leukemia has been noted. The disease is associated with a characteristic chromosomal abnormality - the Philadelphia (Ph") chromosome, which appears as a result of a reciprocal translocation of part of the long arm of chromosome 22 to chromosome 9. The biological mechanism of this chromosomal disorder is not well understood; according to modern data, chromosome rearrangements, including the appearance of Ph" -chromosomes may be a consequence of the activation of cellular oncogenes - genetic loci on human DNA, homologous to DNA viruses that cause malignant tumors in infected animals. The Ph" chromosome is found in chronic myeloid leukemia in all cells of bone marrow lines, except for macrophages and T-lymphocytes, which indicates the likelihood of mutation of an early pluripotent hematopoietic precursor cell.The development of chronic myeloid leukemia goes through two phases - chronic and acute (blast crisis). The dominant phase is the result of tumor progression; during this period, the disease resembles acute leukemia, since blast cells are found in large numbers in the bone marrow and in the periphery. The malignant nature of the blast phase is reflected in cytogenetic changes: in addition to the Ph chromosome, aneuploidy and other karyotype abnormalities are often detected (trisomy of chromosomes 8, 17, 22).
Chronic myeloid leukemia clinic
By the time of diagnosis, patients usually already have neutrophilic leukocytosis and an enlarged spleen. In the initial period, there may be no complaints and the disease is diagnosed by chance during a blood test, then general symptoms appear - weakness, fatigue, weight loss, abdominal discomfort. Splenomegaly is often significant, and splenic infarctions occur. Usually the liver is also enlarged, leukemic infiltration of other organs is possible - heart, lungs, nerve roots.Laboratory data in chronic myeloid leukemia
In the advanced stage of chronic myeloid leukemia, the number of leukocytes reaches 200-400-109/l, and in some cases - 800-1000-109/l. The leukogram shows a shift to myelocytes and promyelocytes; single myeloblasts may be found, usually only with high leukocytosis.An important hematological sign that appears already in the early stages of the disease is an increase in the content of basophils, as well as eosinophils of varying degrees of maturity. The number of platelets is normal or often increased over a long period of the disease; thrombocytopenia occurs in the final stage or as a result of treatment with chemotherapy. Anemia also in most cases appears as the process progresses. The development of anemia may be associated with the influence of a hyperplastic spleen, as well as latent hemolysis. In chronic myeloid leukemia, leukocytosis may be accompanied by an increase in the level of cyanocobalamin in the serum, as well as an increase in the cyanocobalamin-binding capacity of the serum, hyperuricemia. Almost all patients experience a significant decrease in alkaline phosphatase activity in granulocytes.
When examining bone marrow obtained by sternal puncture, an increased number of cells (myelokaryocytes) is revealed, while the cytological picture is almost identical to the blood picture, but unlike peripheral blood smears, there are erythroblasts and megakaryocytes. Chronic myeloid leukemia is characterized by an increase in the number of megakaryocytes, which persists for a significant period of the disease. The decrease in their number in the bone marrow occurs in parallel with a decrease in the number of blood platelets in the peripheral blood during exacerbation of the leukemic process. In bone marrow trephine, even with a relatively low level of leukocytes in the blood, pronounced three-line hyperplasia of myeloid tissue and the absence of fat are usually noted. When puncture of an enlarged spleen in the expanded stages of the disease find a predominance of myeloid cells.
Chronic myeloid leukemia is the only leukemia in which a chromosomal marker of leukemic cells (Ph"-chromosome) is detected with great consistency (in 90% of cases). The Ph"-negative variant of chronic myeloid leukemia occurs in children and adults, is characterized by an unfavorable course and a short average life expectancy of patients The chronic phase of the disease lasts 3-5 years, after which an exacerbation of the disease occurs, a blast crisis develops, during which more than 85% of patients die. In some patients, the transition to the blast phase takes only a few weeks from the appearance of the first signs of the disease. Sometimes the disease is first diagnosed at this phase; the difference from acute leukemia is the presence of the Ph chromosome. There is no specific test that can be used to predict the onset of a blast crisis, at the same time, its early signs are known - increasing leukocytosis, splenomegaly, progressive anemia, thrombocytopenia, refractory to previously effective therapy.Some patients may develop extramedullary tumors, often in the lymph nodes or skin, or develop osteolysis.
The power phase is myeloid or lymphoid in nature (origin). Myeloblastic crisis resembles acute myeloid leukemia; in 1/3 of cases, blast cells have features of lymphoblasts, contain TdT and common acute lymphocytic leukemia antigen; The characteristics of blast cells are important when choosing therapy for blast crisis.