Chronic myeloid leukemia (chronic myeloid leukemia, CML) is a hematopoietic clonal disease characterized by the rapid and unregulated proliferation of predominantly myeloid cells in the bone marrow. The main manifestation of the disease is proliferation (proliferation by cell division) of mature granulocytes and their precursors. Distinctive characteristics of chronic myeloid leukemia are the presence of the “Philadelphia chromosome,” which is observed in most patients, as well as the three-stage development of the disease.
1.What is chronic myeloid leukemia?
Chronic myeloid leukemia is a disease in which the bone marrow produces too many white blood cells.
Chronic myeloid leukemia, or as it is also called – chronic granulocytic leukemia
is a slowly progressive disease of the blood and bone marrow that usually occurs in middle-aged people and is rarely diagnosed in children.
Normally, the bone marrow produces immature blood stem cells, which mature over time. A blood stem cell can become a myeloid stem cell or a lymphoid stem cell. The lymphoid stem cell will become a white blood cell in the future, and the myeloid stem cell will become one of the three types of mature blood cells
:
- Red blood cells that carry oxygen and other necessary substances for all tissues of the body;
- Platelets, which form blood clots to stop bleeding;
- Granular leukocytes (white blood cells) that fight infections and diseases.
Thus, blood stem cells go through several stages of development to become red blood cells, platelets or white blood cells.
In chronic myeloid leukemia, too many blood stem cells become a type of white blood cell called granulocytes. These granulocytes are abnormal cells that cannot become healthy white blood cells. They are also called leukemia cells. Leukemia cells can accumulate in the blood and bone marrow and interfere with the development of normal white blood cells, red blood cells, and platelets. When this happens, anemia, easy bleeding, or frequent infections may occur.
This is how we can generally explain what chronic myeloid leukemia is.
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What is CML and how to fight it
Oncohematologist Mikhail Fominykh about chronic myeloid leukemia
Mikhail Fominykh is a researcher at the Russian Research Institute of Hematology and Transfusiology, St. Petersburg. A practicing oncohematologist who devoted his scientific activity to chronic myeloid leukemia, and defended his dissertation on this topic in 2021. During the discussion, he revealed the main symptoms of CML, talked about risk areas and restrictions, and also explained whether it is possible to give birth to a healthy child with this diagnosis.
What are the main symptoms of CML?
Often the person himself is not particularly worried about anything. Very often, a patient comes to us from another specialist: a therapist or a surgeon. People undergo routine tests and find out that they have an increased number of white blood cells. Having detected elevated leukocytes, the therapist or surgeon refers the patient to a hematologist.
If we talk about symptoms, it may be increased fatigue, sweating, unmotivated rises in body temperature to 38 without obvious signs of infection, heaviness in the left hypochondrium due to the fact that the spleen increases in size. If you monitor your health and get tested every year, chronic myeloid leukemia can be detected at an early stage. Today, 95% of CML cases are diagnosed in the chronic phase and only 5% in advanced, advanced phases. These are the acceleration and blast crisis phases, when symptoms of tumor intoxication begin to appear.
The most striking symptom of the early stage of CML is unmotivated weight loss within six months. If you are not on a diet and are not working on losing weight, but are losing kilograms, and in addition to this, there is increased sweating and a temperature above 38 - this is a reason to be wary and go get tested.
CML in the “advanced” stage is manifested by weakness and increased fatigue due to anemia, increased bleeding from the gums or nose, and bruising may occur. In principle, these symptoms are characteristic of all hematological diseases that are associated with damage to the bone marrow.
How elevated should white blood cells be to suspect CML?
Today, the norm of leukocytes is from 4 to 9 per ten to the ninth power per liter. But you need to understand that these numbers depend on many factors: previous infection, surgery. Just based on the number of leukocytes, no one will say that you have leukemia - in any case, additional examination will be necessary. If increased leukocytosis 10-11 appears once, this is not a reason to run to a hematologist, since this may be a completely normal reaction of the body to a viral or bacterial infection. But if leukocytosis above 15 is observed within three months, then this is a reason to consult a hematologist. We recommend monitoring your blood counts and taking tests at least once a year in order to identify a malfunction in time and begin treatment, if necessary.
Is it possible to say that someone is at risk? Is there a predisposition? Does the environment have an impact?
Heredity plays absolutely no role here. If parents had CML, then it is far from a fact that their children will have it: the hereditary theory has not yet been confirmed. The same applies to all other existing theories: viral, bacterial.
Not long ago there was a terrible story when children with leukemia were evicted from their apartments because the residents of the house believed that cancer could be transmitted by airborne droplets. This, of course, is not true: cancer is not transmitted in this way. If oncological diseases were transmitted by airborne droplets, then I and other oncologists would probably already have died: I saw my first oncological patient in my third year, over 15 years of practice I have seen thousands of them and, fortunately, I am still alive, I am healthy and have no cancer diagnosis.
After exposure to ionizing radiation, the risk does increase: after Chernobyl, Hiroshima and Nagasaki, there was a surge in the development of acute leukemia. This is a confirmed fact, but heredity has no effect on the occurrence of leukemia. Other theories have not yet been confirmed either. Doctors, unfortunately, have not yet identified the cause.
Can we say that CML is an accident, like a brick on your head?
Yes, that's exactly it. I am sitting in front of you now, and you are sitting in front of your gadgets, and a certain number of mutations are happening inside each organism right at this time. This happens while we sleep, eat, or walk down the street. As long as our immune system copes with emerging mutations, everything is fine. When a failure occurs and the system can no longer cope, a tumor process begins to develop. In the case of hematological diseases, a mutation of one cell is enough for this. And it really is like a brick to your head. Chronic leukemia occurs spontaneously; we cannot predict it.
How is treatment for CML constructed?
Imatinib is prescribed in the first line of therapy. If before 1999, after diagnosis, patients lived for 3-4 years, today we can talk about 20-year survival. Patients with CML continue to live a full, quiet life and die just like their peers from cardiovascular diseases, diabetes, and so on. Treatment with Imatinib occurs on an outpatient basis. The patient receives the drug at the pharmacy, takes it at home and lives, in general, like a completely ordinary person. In addition to Imatinib, there are second and third generation drugs. And even on the fourth, they are still undergoing clinical trials.
Is it possible to get pregnant with CML?
When treating with new drugs that are undergoing clinical trials, contraception must be used because we do not yet know how these new drugs may affect the fetus. In the case of already well-known ones, it is necessary to make a decision together with the attending physician, hematologist and gynecologist managing the pregnancy. For example, Ekaterina Yuryevna Chelysheva, who works at the National Medical Research Center for Hematology, has vast experience and a large register of patients with chronic myeloid leukemia who became pregnant and gave birth to healthy children. If the situation allows you to safely discontinue therapy for the period of conception and at least the first trimester, monthly monitoring is necessary. If we see that the molecular response is lost, then for vital indications the therapy will have to be returned.
Unfortunately, complete cancellation is not happening as quickly as we would like. In the case of first-generation tyrosine kinase inhibitors, it takes a little longer. With the second generation - a little earlier: approximately three to five years of constant use. We achieve a molecular response, cancel therapy, and there you go. We are lifting restrictions regarding pregnancy and, in general, most restrictions. This is an ordinary recovered person cured of cancer. It is possible to get pregnant. The only thing that is required is constant monitoring by a hematologist.
Treatment with drugs of the second and subsequent generations allows one to preserve reproductive functions, although previously this seemed nonsense. Now even recommendations for the treatment of cancer recommend discussing their reproductive plans with patients, and only after that prescribing the drug. Today there are drugs that do not have such a strong effect on fertility, and a woman still has the opportunity to become pregnant and bear a healthy child. Nowadays, preservation of reproductive functions is the norm and one of the goals in the treatment of patients with CML. Isn't this happiness?
Are there any restrictions that CML imposes or are there none? What is life like with CML and after CML if we achieve complete remission and stop drug treatment?
I say so rosyly that everyone has won, everyone has won, but to achieve this, close cooperation between the attending physician and the patient himself is necessary. Any changes in life must be discussed with your doctor; you cannot make decisions on your own - only after consultation with your doctor.
The only strict restriction that really exists is the consumption of grapefruit juice. This is strictly prohibited. To put it simply, grapefruit juice interferes with the absorption of drugs with tyrosine kinase inhibitors, and they become ineffective: that is, you take the drug, but it does not work as it should. There are also a number of drugs that can enhance or decrease the effect of drugs, so before starting treatment with a hematologist, you must inform your hematologist about all the medications that you take on a regular basis. If the duration of taking the drugs does not exceed a week, then this does not affect anything, but if therapy is prescribed on an ongoing basis, then a conflict may arise. This is especially true for antihypertensive drugs to normalize blood pressure.
If we talk about sports, then you can gradually return to it after everything - the size of the spleen, blood tests, general well-being - returns to normal. Moderate physical activity is welcome. Our colleagues from the USA recently conducted studies that proved that yoga, breathing exercises, and qigong have a positive effect on the quality of life of patients with myeloproliferative diseases.
Is it possible to go to the sea and undergo sanatorium-resort treatment?
This question is not completely clear. Previously, every cancer diagnosis put an end to any physiotherapy, any sanatorium-resort treatment. Now the only thing I forbid everyone, and not only my patients, but also healthy healthy people, is to avoid increased exposure to sunlight. Swim in the sea as much as you like, but you should protect yourself from the sun. And now we are talking not only about those who are in remission, but also about those who are under treatment and taking medications. If you feel well, your blood test is normal, then the sea is welcome. But active sun should be avoided - this has a detrimental effect on everyone without exception. Increased exposure to sunlight and ultraviolet radiation increases the risk of developing melanoma. This has been proven.
Can CML be completely cured?
Chronic myeloid leukemia is a disease you can live with, and we teach it. There are schools for diabetics, schools for patients with arterial hypertension, and now we run schools for patients with chronic myeloid leukemia: we give lectures, advise patients, educate them so that they know more about the disease than we do. If you have CML, you need to monitor your condition and take control tests every six months. Currently, worldwide research is being conducted on the possibility of completely canceling therapy. In approximately half of patients, therapy is discontinued. In the other half of cases, during the first six months, unfortunately, you have to return to therapy because a relapse occurs. Everything is very individual.
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2. Symptoms of the disease
Possible signs of chronic myeloid leukemia may include fatigue, fever, and increased sweating at night.
.
But all these signs may indicate other health problems, not just myeloid leukemia. But in any case, it is better to consult a doctor if you have the above symptoms, and also if you notice causeless weight loss, pain or a feeling of fullness below the ribs on the left side of the body
. It also happens that chronic myeloid leukemia does not cause any symptoms at all.
Most people with chronic myeloid leukemia have a gene mutation in their bodies,
called the "Philadelphia chromosome". This causes the bone marrow to produce the enzyme tyrosine kinase, which causes too many stem cells to develop into white blood cells (granulocytes). The Philadelphia chromosome is not passed on from parents to children, but develops on its own as a genetic defect.
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3. Diagnosis of chronic myeloid leukemia
To diagnose chronic myeloid leukemia, the patient's blood and bone marrow are examined. For these purposes the following can be done:
- Complete blood test
(it will help determine the number of different types of cells in the blood); - A biochemical blood test
is a study that allows you to measure the amount of certain substances released into the blood by organs and tissues; - Bone marrow biopsy
. During this procedure, a small sample of bone marrow, blood, and bone is taken using a long, hollow needle inserted into the pelvic bone or breastbone. The samples are then examined under a microscope to look for abnormal cells. During research, samples taken can be subjected to cytogenetic analysis (to look for chromosomal changes), studies of genes and chromosomes using fluorescence and chemical exposure, which also helps to identify changes in the structure and function of genes; - In addition, a general examination
will help the doctor evaluate the patient's overall health and see an enlarged spleen, one of the common signs of chronic myelogenous leukemia.
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4. Treatment of the disease
Treatment of chronic myeloid leukemia is selected individually for each patient, and generally depends on the patient’s age, the phase of chronic myeloid leukemia, general health and the size of the spleen at the time of diagnosis.
Depending on the phase, treatment for chronic myeloid leukemia may include
:
- Chronic phase of chronic myeloid leukemia
- targeted therapy with a tyrosine kinase inhibitor; high doses of chemotherapy with donor stem cell transplantation; biological therapy (interferon) with or without chemotherapy; chemotherapy; splenectomy; - Accelerated stage-by-stage chronic myeloid leukemia
– transplantation of donor stem cells; targeted therapy with a tyrosine kinase inhibitor; tyrosine kinase inhibitor therapy followed by transplantation of donor stem cells; biological therapy (interferon with or without chemotherapy; high-dose chemotherapy; chemotherapy; transfusion of blood or blood components to replace white or red blood cells to relieve symptoms of the disease; - Blaster phase of chronic myeloid leukemia
- targeted therapy with a tyrosine kinase inhibitor; chemotherapy using one or more drugs; high doses of chemotherapy; transplantation of donor stem cells; chemotherapy as palliative treatment to relieve symptoms of the disease; - Relapse of chronic myeloid leukemia
- targeted therapy with a tyrosine kinase inhibitor; donor stem cell transplantation; donor lymphocytes; biological therapy with interferon.
Stages of chronic myeloid leukemia
Depending on the clinical manifestation of chronic myeloid leukemia and laboratory tests, three main phases of disease development are distinguished: chronic (stable) phase, acceleration phase and blast crisis. It should be noted that the patient goes through all three phases in the absence of treatment, but with timely therapy, the progression of the disease can be stopped at the stage at which CML was diagnosed.
Chronic phase
In most cases, chronic myeloid leukemia is diagnosed at the chronic stage. During a standard blood test, a shift of the formula to the left is detected, characterized by the presence of neutrophilic leukocytosis with the presence of immature cells of the myeloid series. The patient's stable condition can last an average of 4-5 years. This phase of chronic myeloid leukemia can occur with a few symptoms, including: enlarged spleen, enlarged liver, anemia, general mild malaise, a feeling of fullness in the abdomen, loss of appetite, sweating.
Acceleration phase
There are several diagnostic criteria that characterize the transition of the disease from chronic to accelerated stage. The most common is the criterion developed at the Anderson Cancer Center (University of Texas) and includes any of the following indicators:
- uncontrolled growth of leukocytes in the blood, regardless of therapy;
- platelets in the blood are more than a million, but less than one hundred thousand per microliter of blood (regardless of therapy);
- a sharp increase in the size of the spleen;
- more than 20% basophils in the bone marrow or blood;
- the formation of new chromosomal abnormalities, in addition to the “Philadelphia chromosome”.
Among the general symptoms, patients may note severe fatigue, frequent bleeding, and susceptibility to infectious diseases. The acceleration phase can last from several weeks to several months, during which the patient requires more intensive treatment. In some cases, chronic myeloid leukemia progresses, bypassing the acceleration phase, to blast crisis.
Blast crisis
Blast crisis is the terminal stage of chronic myeloid leukemia, proceeding similar to acute leukemia and characterized by a rapid course of the disease and short survival (3-6 months).
This stage is determined by the presence of one of the following signs:
- the presence of more than 20% lymphoblasts or myeloblasts in the blood or bone marrow;
- detection of large groups of blasts during bone marrow biopsy.
Among the symptoms of a blast crisis, in addition to the symptoms characteristic of the acceleration phase, there is a high temperature, enlarged lymph nodes, and itching of the whole body.
