Treatment of chronic myeloid leukemia depending on the stage. Chronic myeloid leukemia: treatment and prognosis
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:
Less common symptoms of the chronic phase of myeloid leukemia
:- 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?
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:
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| 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 the patient to take them in accordance with the selected 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:
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| 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
Bone marrow transplantation makes it possible for patients with chronic myeloid leukemia to recover completely. The effectiveness of transplantation is higher in the chronic phase of the disease, in other phases it is much lower. 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
It is carried out in cases of no effect from chemotherapy and in case of an enlarged spleen after taking medications (cytostatics). Method of choice for the development of a local tumor (granulocytic sarcoma). 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 itchy skin 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
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.
The goal of treatment for chronic myeloid leukemia is to remove all abnormal cells containing the BCR-ABL gene, which causes excess blood cell production. In most cases, it is not possible to eliminate all leukemia cells, but long-term remission of the disease can be achieved.
Targeted drugs
Targeted drugs affect specific molecular mechanisms of growth and division of malignant cells. The “target” of drugs used to treat chronic myeloid leukemia is a protein encoded by the BCR-ABL gene - tyrosine kinase. Targeted drugs that block the action of tyrosine kinase:
- Imatinib (Gleevec)
- Dasatinib (Sprycel)
- Nilotinib (Tasigna)
- Bosutinib (Bosulif)
- Omaxetine (Sinribo)
Targeted drugs are in most cases first-line drugs. If there is no response to treatment with one targeted drug, your doctor may prescribe another drug or other treatments. Side effects include swelling, nausea, muscle cramps, skin rash, weakness, diarrhea.
Doctors have not determined when it is safe to stop taking targeted drugs, so most patients continue to take them even when blood tests show persistent remission.
Bone marrow transplantation
Bone marrow transplantation offers the only chance for a permanent cure for chronic myelogenous leukemia, but it remains a reserve option for patients who have not responded to other treatments because it is associated with a high risk of developing serious complications. Transplants use high doses of chemotherapy drugs to destroy the patient's own bone marrow. Then blood cells from the donor or your own, prepared in advance, are injected intravenously.
Chemotherapy
Chemotherapy is usually combined with other treatments. Chemotherapy drugs to treat chronic myeloid leukemia are usually taken orally as tablets. Side effects vary depending on the specific drug.
Biological therapy
Biological therapy involves the involvement of the immune system in the fight against cancer. For this purpose, interferon preparations are used - synthetic analogues of substances produced by the body's immune system. Interferons may help slow the proliferation of leukemia cells. Interferons are indicated in cases where other treatments do not work or the patient cannot take the drugs, for example, due to pregnancy. Side effects of interferons include weakness, fever, flu-like symptoms, and weight loss.
Clinical researches
Clinical trials study new treatments for diseases or new ways to use existing treatments. Participation in a clinical trial may give you the opportunity to try the latest treatment, but cannot guarantee a cure. Talk to your doctor about what clinical trials are available to you. Discuss the pros and cons of participating in clinical research.
Lifestyle and folk remedies
Many people have to live with chronic myeloid leukemia for many years. Many will have to continue treatment with imatinib indefinitely. Sometimes you will feel sick even if you don't look like it. Sometimes you will become tired of your illness. The tips given here will help you get in the best mood and cope with the disease:
- Discuss possible side effects of the disease with your doctor. Powerful leukemia drugs can cause a variety of side effects, but you don't have to endure them. Side effects can often be managed with other medications.
- Do not stop treatment on your own. If you experience any side effects, such as skin rash or severe weakness, do not stop treatment without consulting a specialist. Also, do not stop taking your medications if you feel better and think your condition has been cured. If you stop taking your medications, your illness may return quickly and unexpectedly, even if you are in remission.
- Get help if you are having trouble coping with your illness.. Chronic illness is a source of stress and emotional overload. Tell your doctor about your feelings. Ask for a referral to a therapist or other professional you can talk to.
Alternative medicine
None of the alternative medicine treatments can cure chronic myeloid leukemia, but they can help you cope with stress and the side effects of treatment. Discuss methods such as:
- Acupuncture
- Aromatherapy
- Massage
- Meditation
- Relaxation techniques
- Prevention of Chronic myeloid leukemia
- Which doctors should you contact if you have Chronic myeloid leukemia?
What is Chronic myeloid leukemia
Chronic myeloid leukemia (CML) ranks third among all leukemias. It accounts for about 20% of blood cancer cases. At the moment, more than 3 thousand patients are registered in Russia. The youngest of them is only 3 years old, the oldest is 90.
Incidence of CML is 1-1.5 cases per 100,000 population per year (15-20% of all cases of hemoblastosis in adults). Mostly middle-aged people are affected: the peak incidence occurs at the age of 30-50 years, about 30% are patients over 60 years of age. In children, CML is rare, accounting for no more than 2-5% of all leukemias. Men get sick slightly more often than women (ratio 1:1.5).
What causes chronic myeloid leukemia?
Like the vast majority of other leukemias, chronic myeloid leukemia occurs as a result of acquired (i.e., not congenital) damage to the chromosomal apparatus of a single bone marrow stem cell.
The exact reason for this chromosomal change in patients with CML is still unknown. Most likely, there is a random exchange of genetic material between chromosomes, which at a certain stage of the cell's life are located in close proximity to each other.
The issue of the influence on the incidence of CML by factors such as low doses of radiation, weak electromagnetic radiation, herbicides, insecticides, etc. remains controversial. An increase in the incidence of CML in individuals exposed to ionizing radiation has been reliably proven. Among chemical agents, a connection with the occurrence of CML has been established only for benzene and mustard gas.
Substrate for chronic myeloid leukemia consist mainly of maturing and mature cells of the granulocytic series (metamyelocytes, band and segmented granulocytes).
Pathogenesis (what happens?) during Chronic myeloid leukemia
It is believed that the t(9;22) translocation, leading to the formation of the chimeric BCR-ABL1 gene, plays a key role in the occurrence of chronic myeloid leukemia. In this case, the 1st exon of the ABL1 gene is replaced by a different number of 5"-terminal exons of the BCR gene. Chimeric Bcr-Abl proteins (one of them is the p210BCR-ABL1 protein) contain N-terminal Bcr domains and C-terminal Abl1 domains.
The ability of chimeric proteins to cause tumor transformation of normal hematopoietic stem cells has been demonstrated in vitro.
The oncogenicity of the p210BCR-ABL1 protein is also evidenced by experiments on mice that received a lethal dose of radiation. When they were transplanted with bone marrow cells that were infected with a retrovirus carrying the BCR-ABL1 gene, half of the mice developed myeloproliferative syndrome, which resembled chronic myeloid leukemia.
Other evidence for the role of the p210BCR-ABL1 protein in the development of chronic myeloid leukemia follows from experiments with antisense oligonucleotides complementary to the BCR-ABL1 gene transcript. These oligonucleotides have been shown to suppress the growth of tumor cell colonies, while normal granulocyte and macrophage colonies continue to grow.
The fusion of the BCR gene with the ABL1 gene results in an increase in the tyrosine kinase activity of the Abl1 protein, a weakening of its ability to bind to DNA, and an increase in binding to actin.
At the same time, the detailed mechanism of the degeneration of normal bone marrow cells into tumor cells is unknown.
The mechanism of transition of the disease from the advanced stage to blast crisis is also unclear. The tumor clone is characterized by fragility of chromosomes: in addition to the t(9;22) translocation, trisomy of chromosome 8 and deletion of 17p may appear in tumor cells. The accumulation of mutations leads to changes in the properties of tumor cells. According to some researchers, the rate of development of the blast crisis depends on the location of the break point of the BCR gene. Other researchers refute these data.
In a number of patients, the development of blast crisis is accompanied by various mutations of the TP53 gene and the RB1 gene. Mutations of RAS genes are rare. There are isolated reports of the appearance of the p190BCR-ABL1 protein in patients with chronic myeloid leukemia (it is often found in patients with acute lymphoblastic leukemia and sometimes in patients with acute myeloid leukemia), as well as mutations of the MYC gene.
Before blast crisis, DNA methylation may occur at the BCR-ABL1 gene locus.
There is also information about the participation of IL-1beta in the progression of chronic myeloid leukemia.
The presented data indicate that tumor progression is caused by several mechanisms, but the exact role of each of them is unknown.
Symptoms of Chronic myeloid leukemia
Moment of occurrence chronic myeloid leukemia, like any other leukemia, has no symptoms and always goes unnoticed. Symptoms develop when the total number of tumor cells begins to exceed 1 kilogram. Most patients complain of general malaise. They get tired faster and may experience shortness of breath during physical work. As a result of anemia, the skin becomes pale. Patients may experience discomfort in the left side of the abdomen caused by an enlarged spleen. Patients often lose weight, notice increased sweating, weight loss and an inability to tolerate heat. On clinical examination, most often the only pathological sign is an enlarged spleen. An increase in the size of the liver and lymph nodes in the early stages of CML practically does not occur. In about a quarter of patients, chronic myeloid leukemia is discovered completely by chance, during a routine medical examination. Sometimes the diagnosis of CML is made at a more aggressive stage - acceleration or blast crisis.
Chronic myeloid leukemia (chronic myelosis) occurs in two stages.
The first stage is benign, lasts several years, and is characterized by an enlarged spleen.
The second stage is malignant and lasts 3-6 months. The spleen, liver, lymph nodes are enlarged, leukemic infiltrates of the skin, nerve trunks, and meninges appear. Hemorrhagic syndrome develops.
Infectious diseases are frequently reported. Typical signs of intoxication are weakness, sweating. Sometimes the first symptom is a slight pain, heaviness in the left hypochondrium, which is associated with an enlarged spleen; subsequently, splenic infarctions occur. For no apparent reason, the temperature rises and bone pain appears.
A typical case is characterized by neutrophilic leukocytosis (increased level of neutrophilic leukocytes) with the appearance of young forms of neutrophils, accompanied by an increase in the number of platelets and a decrease in the content of lymphocytes. As the disease progresses, anemia and thrombocytopenia increase. In children, a juvenile form of chronic myeloid leukemia is more often observed without an increase in the number of platelets, but with an increased content of monocytes. The number of basophils often increases, and there is an increased level of eosinophils. In the first benign stage, bone marrow cells correspond to normal in all respects. In the second stage, blast forms appear in the bone marrow and blood, and a rapid increase in the number of leukocytes in the blood is noted (up to several million in 1 μl). Characteristic signs of the final stage are the detection of fragments of megakaryocyte nuclei in the blood and inhibition of normal hematopoiesis.
The disease is chronic with periods of exacerbation and remission. The average life expectancy is 3-5 years, but there are isolated cases of long-term chronic myeloid leukemia (up to 10-20 years). The clinical picture depends on the stage of the disease.
Forecast is ambiguous and depends on the stage of the disease. During the first two years after diagnosis, 10% of patients die, each subsequent year - slightly less than 20%. Median survival is approximately 4 years.
Prognostic models are used to determine the stage of the disease and the risk of death. Most often, these are models based on multivariate analysis of the most important prognostic features. One of them, the Sokal index, takes into account the percentage of blast cells in the blood, the size of the spleen, the number of platelets, additional cytogenetic disorders and age. The Tour model and the combined Kantarjan model take into account the number of unfavorable prognostic signs. These characteristics include: age 60 years or older; significant splenomegaly (the lower pole of the spleen protrudes from the left hypochondrium by 10 cm or more); the content of blast cells in the blood or bone marrow equal to or greater than 3% and 5%, respectively; basophil content in the blood or bone marrow equal to or greater than 7% and 3%, respectively; platelet level equal to or greater than 700,000 1/μl, as well as all signs of the acceleration stage. If these signs are present, the prognosis is extremely unfavorable; The risk of death during the first year of the disease is three times higher than usual.
Diagnosis of Chronic myeloid leukemia
Blood and bone marrow picture In a typical case, neutrophilic leukocytosis is characterized by the appearance of young forms of neutrophils, accompanied by hyperthrombocytosis and lymphocytopenia. As the disease progresses, anemia and thrombocytopenia increase. In children, the juvenile form of chronic myeloid leukemia without hyperthrombocytosis, but with high monocytosis, is more often observed. The number of basophils often increases, and eosinophilia occurs. In the first benign stage, bone marrow cells correspond to normal in all respects. In the second stage, blast forms appear in the bone marrow and blood, and a rapid increase in the number of leukocytes in the blood is noted (up to several million in 1 μl). Characteristic signs of the terminal stage are the detection of fragments of megakaryocyte nuclei in the blood and inhibition of normal hematopoiesis.
The diagnosis of chronic leukemia is established on the basis of complaints, examination, blood tests, biopsy, and cytogenetic analysis. Ancillary examination methods such as PET-CT, CT, and MRI also help in establishing a diagnosis.
The diagnosis is made by a blood picture. Bone marrow puncture is of decisive importance. Differential diagnosis is made with lymphogranulomatosis and lymphosarcomatosis.
Treatment of Chronic myeloid leukemia
In the advanced stage of the disease, small doses of myelosan are prescribed, usually for 20-40 days. When leukocytes drop to 15,000-20,000 in 1 μl (15-20 G/l), they switch to maintenance doses. In parallel with myelosan, irradiation of the spleen is used. In addition to myelosan, it is possible to prescribe myelobromine, 6-mercaptopurine, hexaphosphamide, and hydroxyurea. At the stage of blast crisis, a combination of drugs gives a good result: vincristine-prednisolone, cytosar-rubomycin, cytosarthioguanine. Bone marrow transplantation is used.
There are many diagnoses whose names mean little to ordinary citizens. One such disease is chronic myeloid leukemia. Reviews from patients with this disease are nevertheless capable of attracting attention, since this disease can not only cause significant damage to health, but also lead to a fatal outcome.
The essence of the disease
If you hear a diagnosis such as “chronic myeloid leukemia,” then it is important to understand that we are talking about a serious tumor disease of the hematopoietic system, which affects the hematopoietic stem cells of the bone marrow. It can be classified as a group of leukemias, which are characterized by large formations of granulocytes in the blood.
At the very beginning of its development, myeloid leukemia manifests itself through an increase in the number of leukocytes, reaching almost 20,000/μl. Moreover, in the progressive phase this figure changes to 400,000/μl. It is worth noting the fact that both the hemogram and the myelogram show a predominance of cells with different degrees of maturity. We are talking about promyelocytes, metamyelocytes, band and myelocytes. In the case of the development of myeloid leukemia, changes are detected in the 21st and 22nd chromosomes.
This disease in most cases leads to a noticeable increase in the content of basophils and eosinophils in the blood. This fact is evidence that we are dealing with a severe form of the disease. In patients who suffer from such an oncological disease, splenomegaly develops, and a large number of myeloblasts are recorded in the bone marrow and blood.
How does the disease begin?
Chronic myeloid leukemia pathogenesis is quite interesting. Initially, a somatic mutation of a pluripotent hematopoietic blood stem cell can be identified as a trigger factor in the development of this disease. The main role in the mutation process is played by the cross-translocation of chromosomal material between the 22nd and 9th chromosomes. In this case, the Ph chromosome is formed.
There are cases (no more than 5%) when the Ph chromosome cannot be detected during a standard cytogenetic study. Although molecular genetic research reveals an oncogene.
Chronic myeloid leukemia can also develop due to exposure to various chemical compounds and radiation. Most often this disease is diagnosed in adulthood, extremely rarely in adolescents and children. As for gender, this type of tumor is recorded with equal frequency in both men and women aged 40 to 70 years.
Despite all the experience of doctors, the etiology of the development of myeloid leukemia is still not completely clear. Experts suggest that acute and chronic myeloid leukemia develops due to a disorder of the chromosomal apparatus, which, in turn, is caused by the influence of mutagens or hereditary factors.
Speaking about the effects of chemical mutagens, it is worth paying attention to the fact that quite a few cases have been recorded in which people exposed to benzene or using cytostatic drugs (Mustargen, Imuran, Sarcozoline, Leukeran, etc.) , myeloid leukemia developed.
Chronic myeloid leukemia: stages
With a diagnosis such as “myeloid leukemia,” three stages of development of this disease are distinguished:
Initial. Characterized by an enlarged spleen and a stable increase in leukocytes in the blood. The patient's condition is considered dynamically, without using radical treatment measures. The disease, as a rule, is diagnosed already at the stage of total generalization of the tumor in the bone marrow. At the same time, in the spleen, and in some cases in the liver, extensive proliferation of tumor cells is observed, which is characteristic of the advanced stage.
Expanded. Clinical signs at this stage begin to dominate, and the patient is prescribed treatment using specific drugs. At this stage, the myeloid tissue in the bone marrow, liver and spleen grows, and the fat in the flat bones is virtually completely replaced. There is also a sharp predominance of the granulocytic lineage and three-line proliferation. It is worth noting that in the advanced stage, lymph nodes are extremely rarely affected by the leukemic process. In some cases, myelofibrosis may develop in the bone marrow. There is a possibility of developing pneumosclerosis. As for the infiltration of the liver by tumor cells, in most cases it is quite pronounced.
Terminal. At this stage of the disease, thrombocytopenia and anemia progress. Manifestations of various complications (infection, bleeding, etc.) become obvious. The development of a second tumor from immature stem cells is often observed.
What life expectancy should you expect?
If we talk about people who have had to deal with chronic myeloid leukemia, it is worth noting that modern treatment methods have significantly increased the chances of such patients for a relatively long life. Due to the fact that discoveries have been made in the field of pathogenetic mechanisms of the development of the disease, which have made it possible to develop drugs that can act on the mutated gene, with a diagnosis such as chronic myeloid leukemia, the life expectancy of patients can be 30-40 years from the moment the disease is diagnosed. But this is possible provided that the tumor was benign (slow enlargement of the lymph nodes).
In the case of the development of a progressive or classic form, the average is from 6 to 8 years from the moment the disease was diagnosed. But in each individual case, the number of years that the patient can enjoy is significantly influenced by the measures taken during the treatment process, as well as by the form of the disease.
On average, according to statistics, up to 10% of patients die within the first two years after detection of the disease and 20% in subsequent years. Many patients with myeloid leukemia die within 4 years after the diagnosis was made.
Clinical picture
The development of a disease such as chronic myeloid leukemia occurs gradually. At first, the patient feels a deterioration in his general health, fatigue, weakness, and in some cases moderate pain in the left hypochondrium. After the study, an enlarged spleen is often recorded, and a blood test reveals significant neutrophilic leukocytosis, characterized by a shift in the leukocyte count to the left due to the action of myelocytes with an increased content of basophils, eosinophils and platelets. When the time comes for the full picture of the disease, patients experience loss of ability to work due to sleep disturbances, sweating, a steady increase in general weakness, a significant increase in temperature, pain in the spleen and bones. There is also a loss of weight and appetite. At this stage of the disease, the spleen and liver are significantly enlarged.
At the same time, chronic myeloid leukemia, the symptoms of which differ depending on the stage of development of the disease, already in the initial stage leads to a predominance of eosinophils, granular leukocytes and basophils in the bone marrow. This growth occurs due to a decrease in other leukocytes, normoblasts and red blood cells. If the disease process begins to worsen, the number of immature myeloblasts and granulocytes increases significantly, and hemocytoblasts begin to appear.
Blast crisis in chronic myeloid leukemia leads to total metaplasia. In this case, there is a high fever, during which there are no signs of infection. Hemorrhagic syndrome develops (intestinal, uterine, mucous bleeding, etc.), leukemides in the skin, ossalgia, lymph nodes enlarge, complete resistance to cytostatic therapy and infectious complications are recorded.
If it was not possible to significantly influence the course of the disease (or such attempts were not made at all), then the condition of the patients will progressively worsen, and thrombocytopenia will appear (the phenomena of hemorrhagic diathesis make themselves felt) and severe anemia. Due to the fact that the size of the liver and spleen is growing rapidly, the volume of the abdomen noticeably increases, the condition of the diaphragm becomes high, the abdominal organs are compressed, and, as a consequence of these factors, the respiratory excursion of the lungs begins to decrease. Moreover, the position of the heart changes.
When chronic myeloid leukemia develops to this level, dizziness, shortness of breath, palpitations and headache appear against the background of pronounced anemia.
Monocyte crisis in myeloid leukemia
Regarding the topic of monocytic crisis, it should be noted that this is a rather rare phenomenon, during which young, atypical and mature monocytes appear and grow in the bone marrow and blood. Due to the fact that the bone marrow barriers are broken, at the terminal stage of the disease fragments of megakaryocyte nuclei appear in the blood. One of the most important elements of the terminal stage during a monocytic crisis is the inhibition of normal hematopoiesis (regardless of the morphological picture). The disease process is aggravated due to the development of thrombocytopenia, anemia and granulocytopenia.
In some patients, rapid enlargement of the spleen may be observed.
Diagnostics
The fact of progression of a disease such as chronic myeloid leukemia, the prognosis of which can be quite bleak, is determined through a whole complex of clinical data and specific changes in the process of hematopoiesis. In this case, histological studies, histograms and myelograms must be taken into account. If the clinical and hematological picture does not look clear enough and there is not enough data to confidently make a diagnosis, then doctors focus on detecting the Ph chromosome in monocytes, megakaryocytes, erythrocytes and granulocytes of the bone marrow.
In some cases, it is necessary to differentiate chronic myeloid leukemia. Diagnosis, which can be defined as differential, is aimed at identifying the typical picture of the disease with hyperleukocytosis and splenomegaly. If the option is atypical, then a histological examination of the spleen punctate is performed, as well as a myelogram study.
Certain difficulties can be observed when patients are admitted to the hospital in a state of blast crisis, the symptoms of which are very similar to myeloid leukemia. In such a situation, data from a thoroughly collected anamnesis, cytochemical and cytogenetic studies significantly help. Often chronic myeloid leukemia must be differentiated from osteomyelofibrosis, in which intense myeloid metaplasia can be observed in the lymph nodes, spleen, liver, as well as significant splenomegaly.
There are situations, and they are not uncommon, when a blood test helps to identify chronic myeloid leukemia in patients who have undergone a routine examination (in the absence of complaints and asymptomatic disease).
Diffuse myelosclerosis can be excluded by x-ray examination of bones, which reveals multiple areas of sclerosis in flat bones. Another disease that, although rare, still has to be differentiated from myeloid leukemia, is hemorrhagic thrombocythemia. It can be characterized by leukocytosis with a shift to the left and enlargement of the spleen.
Laboratory tests for the diagnosis of myeloid leukemia
In order to accurately determine the patient’s condition if chronic myeloid leukemia is suspected, a blood test can be performed in several directions:
Blood chemistry. It is used to identify disorders in the liver and kidneys that are a consequence of the use of certain cytostatic agents or were provoked by the spread of leukemia cells.
- Clinical blood test (complete). Necessary for measuring the level of various cells: platelets, leukocytes and red blood cells. In most patients who have had to deal with a disease such as chronic myeloid leukemia, the analysis reveals a large number of immature white cells. Sometimes a low platelet or red blood cell count may occur. Such results are not a basis for determining leukemia without an additional test that is aimed at examining the bone marrow.
Examination of bone marrow and blood samples under a microscope by a pathologist. In this case, the shape and size of the cells are studied. Immature cells are identified as blasts or myeloblasts. The number of hematopoietic cells in the bone marrow is also counted. The term “cellularity” is applicable to this process. In those with chronic myelogenous leukemia, the bone marrow tends to be hypercellular (large concentrations of hematopoietic cells and a high content of malignant cells).
Treatment
For a disease such as chronic myeloid leukemia, treatment is determined depending on the stage of development of tumor cells. If we are talking about mild clinical and hematological manifestations in the chronic stage of the disease, then nutritious nutrition enriched with vitamins, regular follow-up and restorative therapy should be considered as relevant therapeutic measures. Interferon can have a beneficial effect on the course of the disease.
If leukocytosis develops, doctors prescribe Myelosan (2-4 mg/day). If you have to deal with higher leukocytosis, then the dose of Myelosan can rise to 6 or even 8 mg/day. You should expect the manifestation of a cytopenic effect no earlier than 10 days after the first dose of the drug. A decrease in the size of the spleen and a cytopenic effect occurs on average during the 3-6th week of treatment, if the total dose of the drug was from 200 to 300 mg. Further therapy involves taking 2-4 mg of Myelosan once a week, which at this stage has a supporting effect. If the first signs of exacerbation make themselves known, myelosanotherapy is performed.
It is possible to use a technique such as radiation therapy, but only when splenomegaly is identified as the main clinical symptom. For the treatment of patients whose disease is in a progressive stage, poly- and monochemotherapy is relevant. If significant leukocytosis is recorded, if the effect of Myelosan is not sufficiently effective, Myelobromol (125-250 mg per day) is prescribed. At the same time, strict monitoring of peripheral blood parameters is carried out.
If significant splenomegaly develops, Dopan is prescribed (single dose 6-10 g/day). Patients take the drug once for 4-10 days. The intervals between doses are determined depending on the degree and rate of decrease in the number of leukocytes, as well as the size of the spleen. As soon as the decrease in leukocytes reaches an acceptable level, the use of Dopan is stopped.
If a patient develops resistance to Dopan, Myelosan, radiation therapy and Myelobromol, Hexaphosphamide is prescribed for treatment. In order to effectively influence the course of the disease in the progressive stage, the CVAMP and AVAMP programs are used.
If resistance to cytostatic therapy develops in a disease such as chronic myeloid leukemia, treatment in the progression stage will be focused on the use of leukocytopheresis in combination with a specific polychemotherapy regimen. As an urgent indication for leukocytopheresis, clinical signs of stasis in the vessels of the brain (a feeling of heaviness in the head, decreased hearing, headaches), which are caused by hyperthrombocytosis and hyperleukocytosis, can be identified.
If a blast crisis is detected, various chemotherapy programs used for leukemia can be considered relevant. Indications for transfusions of red blood cells, platelet concentrate and antibacterial therapy are infectious complications, the development of anemia and thrombocytopenic hemorrhage.
Regarding the chronic stage of the disease, it is worth noting that at this stage of development of myeloid leukemia, bone marrow transplantation is quite effective. This technique is capable of ensuring the development of clinical and hematological remission in 70% of cases.
An urgent indication for splenectomy in chronic myeloid leukemia is the threat of rupture or rupture of the spleen. Relative indications include severe abdominal discomfort.
Radiation therapy is indicated for those patients in whom extramedullary tumor formations that pose a threat to life have been identified.
Chronic myeloid leukemia: reviews
According to patients, such a diagnosis is too serious to ignore. By studying the testimonies of various patients, the real possibility of defeating the disease becomes obvious. To do this, you need to undergo timely diagnosis and subsequent treatment. Only with the participation of highly qualified specialists is there a chance to defeat chronic myeloid leukemia with minimal losses to health.
