Chronic myelogenous leukemia, BCR-ABL1 positive (often called chronic myeloid leukemia or CML) is a blood cancer where the bone marrow makes too many white blood cells, especially a type called granulocytes. These abnormal cells crowd out normal blood cells and can collect in the spleen and other organs.
Chronic myelogenous leukemia, BCR-ABL1 positive (CML) is a blood cancer where a broken chromosome creates an abnormal gene called BCR-ABL1. This gene makes a protein (a tyrosine kinase) that is “stuck in ON mode” and tells white blood cells to grow too fast. Modern medicines called tyrosine kinase inhibitors (TKIs) block this protein and have turned CML into a long-term, often well-controlled disease for many people.
Other names you may see for the same disease include: chronic myeloid leukemia (CML), chronic myelogenous leukemia, Philadelphia-chromosome–positive CML, Ph-positive CML, BCR-ABL1–positive CML, and chronic myelocytic leukemia. All these names point to the same basic problem: white blood cells that carry a special gene change called BCR-ABL1.
In CML, a piece of chromosome 9 and a piece of chromosome 22 swap places. This makes a new “fusion gene” called BCR-ABL1, also known as the Philadelphia (Ph) chromosome. This gene works like a stuck-on growth signal. It tells the white blood cell precursors to grow and divide all the time, so cell numbers rise in the blood and bone marrow.
CML usually develops slowly at first and often starts in a “chronic phase,” when many people feel well or only mildly unwell. Without proper treatment, it can progress to more aggressive phases called accelerated phase and blast phase, which behave more like acute leukemia and are more dangerous.
Types of chronic myelogenous leukemia, BCR-ABL1 positive
When doctors talk about “types” of CML, they often mean groups based on how advanced the disease is, or on specific lab features. These types help decide treatment and predict outlook.
Chronic phase CML
This is the earliest and most common phase at diagnosis. The white blood cell count is high, but most cells are still fairly mature. Many people have few or no symptoms, and the disease is often found on a routine blood test. Treatment usually works best in this phase, and long-term control is often possible.Accelerated phase CML
In this phase, the leukemia cells become more unstable and blast (very immature) cells start to increase, but not as much as in blast phase. Blood counts may be harder to control, symptoms often get worse, and the risk of progression is higher. Doctors use blood counts, blast percentage, and other features to define this phase.Blast phase (blast crisis) CML
Blast phase behaves like an acute leukemia. A large percentage of cells in blood or bone marrow are blasts. People may become very unwell, with severe anemia, infections, or bleeding. This phase is harder to treat and needs urgent, intensive therapy.Types by BCR-ABL1 transcript (molecular subtype)
The BCR-ABL1 fusion gene can be made in slightly different ways, creating different “transcripts” such as e13a2, e14a2, or rarer forms. Lab reports may mention these codes. They do not change the basic diagnosis of CML, but they can affect how the leukemia is monitored and sometimes how responses are interpreted.Risk-score groups (low, intermediate, high risk)
Doctors use scoring systems such as the Sokal or Hasford score, which combine age, spleen size, platelet count, and blood blast percentage. People are then placed into low-, intermediate-, or high-risk groups. These scores help estimate prognosis and guide which treatment strategy or medicine intensity might be needed.Pediatric vs adult CML
CML can rarely occur in children and teenagers. Pediatric CML tends to be managed in specialized centers, and there are age-specific considerations for growth, development, and long-term side effects. However, the basic biology (BCR-ABL1 fusion, Philadelphia chromosome) is the same as in adults.
Causes and risk factors
For CML, the main true cause is an acquired mutation that creates the BCR-ABL1 fusion gene. Most other items are risk factors, which may raise the chance that this mutation appears, but they do not guarantee disease. In many patients, no clear risk factor is found.
Acquired BCR-ABL1 fusion gene (Philadelphia chromosome)
The direct cause of CML is a DNA change in a bone marrow stem cell that creates the BCR-ABL1 fusion gene. This new gene makes an abnormal enzyme (tyrosine kinase) that signals cells to grow and divide without normal control. This single genetic event is the defining cause of BCR-ABL1–positive CML.Random DNA damage during normal cell division
Bone marrow stem cells divide throughout life. During copying of DNA, small errors can occur at random. Most errors are repaired or harmless, but sometimes a mistake creates the BCR-ABL1 fusion. When this mutated cell survives and multiplies, CML may develop even without any obvious outside trigger.High-dose ionizing radiation
Strong radiation can damage DNA and increase the chance of chromosome breaks and swaps. Studies of atomic bomb survivors and nuclear workers show a higher risk of CML in people who received high radiation doses. Radiation used in cancer treatment can also add risk, although modern techniques try to limit this as much as possible.Occupational exposure to benzene
Benzene is a chemical used in some industries and present in gasoline and some solvents. It is a known cause of certain leukemias, and there is some evidence that long-term benzene exposure may slightly raise the risk of CML as well. Workers in rubber, oil, or chemical plants may be more exposed if protections are poor.Cigarette smoking
Cigarette smoke contains benzene and many other cancer-causing chemicals. Smoking is strongly linked to some leukemias and may contribute to risk for CML by adding ongoing toxin and benzene exposure. Quitting smoking is advised for many health reasons and may help reduce overall blood cancer risk.Older age
CML is more common in middle-aged and older adults. As people age, their stem cells have gone through more divisions and have had more chances to collect DNA damage, which may help explain why CML is mainly a disease of later life.Male sex
CML occurs slightly more often in males than females. The reason is not fully understood. It may relate to patterns of chemical exposure, hormones, or how male and female bodies handle toxins, but the exact mechanism remains unclear.Family history and genetic susceptibility
CML is usually not inherited, and most families have only one affected person. However, rare “familial CML” clusters and data showing higher BCR-ABL1 carriage in relatives suggest there may be inherited factors that slightly increase risk in some families.Previous high-dose chemotherapy or radiotherapy for other cancers
Strong treatments that damage DNA, such as some chemotherapy drugs and high-dose radiotherapy, can sometimes lead to later leukemias. This is more clearly shown for other blood cancers, but similar mechanisms may, in rare cases, contribute to CML development.Occupational radiation exposure
Workers in nuclear plants, radiology, or other radiation-using fields can receive higher lifetime radiation doses if protection is inadequate. Long-term studies suggest increased leukemia risk for such workers when exposure is not well controlled. Proper shielding and monitoring reduce this risk.Obesity and metabolic factors
Obesity and metabolic problems make the body’s environment more inflamed and may slightly increase the risk of some hematologic cancers. Evidence in CML is not as strong as in other leukemias, but obesity appears among possible shared risk factors in population studies of blood cancers.Chronic exposure to other industrial solvents
Long-term contact with some organic solvents, paints, and industrial chemicals is associated with higher leukemia rates in workers. Though data are stronger for acute leukemias, similar DNA-damaging effects may also contribute to CML risk in exposed groups.Environmental pollution and urban air contaminants
Living in heavily polluted areas can mean low-level exposure to many chemicals and fine particles over years. This type of exposure may add to background risk of genetic damage in blood cells, though it is usually one of many small contributors rather than a direct single cause.Living near sources of radiation or industrial emissions
People living close to large nuclear or industrial facilities may, in some situations, have higher exposure to radiation or carcinogens. Some studies suggest slightly higher leukemia rates in such communities, but results are mixed and risk for any one person remains low.Repeated high-dose medical imaging
Diagnostic imaging such as CT scans uses ionizing radiation. Each scan adds a small dose. For most people, the benefit of needed imaging is greater than the risk, but many high-dose scans over a lifetime could slightly increase leukemia risk by causing extra DNA damage.Immune system dysregulation and chronic inflammation
Long-lasting inflammation or immune problems can create a stressed bone marrow environment and may make DNA damage more likely. This link is clearer in some lymphoid cancers, but immune dysfunction is being explored as a possible background factor in myeloproliferative diseases like CML.Co-exposure to smoking and workplace chemicals
When a person both smokes and works around chemicals like benzene, the total exposure load is higher. This combination may act together to raise the chance of leukemia-related DNA damage, though exact risk numbers for CML specifically are not well defined.Previous bone marrow stress or damage
Conditions that seriously stress bone marrow, such as some severe infections or other myeloproliferative disorders, can push stem cells to divide more. This extra cell turnover may provide more chances for errors like the BCR-ABL1 fusion to appear in a susceptible person.Unrecognized genetic variants that affect DNA repair
Some people may carry gene changes that make their DNA repair systems a little less efficient. These variants can make them more sensitive to standard levels of environmental stress, which might help explain why only some people exposed to risk factors develop CML.Unknown or idiopathic causes
In most patients, no clear risk factor is ever found. CML can arise in people with no unusual exposure or family history. This shows that chance events in DNA, combined with basic background risks, play a large role in CML, and many cases are simply idiopathic (of unknown cause).
Symptoms
Symptoms can be very mild at first, especially in chronic phase. Around half of people with CML are found because of an abnormal blood test, not because they felt sick. When symptoms do appear, they usually come from anemia, high white cell counts, or an enlarged spleen.
Tiredness and easy fatigue
Many people feel unusually tired, weak, or drained, even after normal activities. This often comes from anemia, where the blood does not carry enough oxygen, and from the body using extra energy to handle the large number of leukemia cells.Shortness of breath on exertion
Climbing stairs or walking can feel harder than before. Because the red blood cell level may be low, muscles and organs get less oxygen, so breathing faster is the body’s way to try to make up for this.Pale skin (pallor)
With anemia, the skin, lips, and inner eyelids can look paler than usual. This is because there is less red pigment (hemoglobin) in the blood. Family or friends may notice this before the patient does.Unplanned weight loss
Some people lose weight without trying. The body is working hard and using more energy. The enlarged spleen and general feeling of illness can also reduce appetite, which adds to weight loss.Loss of appetite and early fullness
An enlarged spleen presses on the stomach. People may feel full after only a small amount of food or lose interest in eating. This symptom often goes along with weight loss.Fullness or discomfort in the left upper abdomen
The spleen sits on the left side of the upper belly. When it becomes large because it is filled with leukemia cells, it can cause a dull ache, heaviness, or a sense of pressure under the left ribs. Sometimes this pain can spread to the left shoulder.Night sweats
People may wake up with their clothes or bed sheets soaked in sweat, even when the room is cool. Night sweats are a common sign of blood cancers and reflect the body’s response to abnormal cells and cytokines.Low-grade fevers or feeling feverish
Some patients have mild fevers that come and go, or they just feel hot and unwell. This can happen because the immune system is activated against leukemia cells, or because normal infection-fighting cells do not work properly.Frequent infections
Even though the white cell count is high, many of the cells are abnormal and do not fight germs well. This can lead to repeated infections such as colds, pneumonia, or skin infections, or infections that take longer than usual to clear.Easy bruising or bleeding
Platelets, which help the blood to clot, can be low or not function properly. People may notice nosebleeds, bleeding gums, heavy menstrual periods, or bruises and tiny red spots (petechiae) on the skin after very minor bumps.Bone or joint pain
The bone marrow is very active and crowded with leukemia cells. This can cause aching or sharp pain in bones or joints, especially in the long bones and sternum. Sometimes pain is related to high levels of uric acid, which can irritate joints.General feeling of being unwell (malaise)
People often describe a vague feeling that “something is wrong,” with low energy, poor concentration, and reduced ability to do daily tasks. This whole-body feeling reflects anemia, inflammation, and the stress of a chronic cancer.Headaches or dizziness
Very high white blood cell counts can make the blood thicker, a problem called hyperviscosity. This can slow blood flow to the brain and cause headaches, dizziness, or visual changes, especially when counts are extremely high.Gout-like joint swelling
As leukemia cells break down, they release substances that become uric acid. High uric acid can form crystals in joints, leading to sudden painful swelling in areas like the big toe, ankle, or knee, similar to gout attacks.No symptoms but abnormal blood test
Many people have no complaints at all. A routine blood test done for a check-up or another reason shows a very high white blood cell count or abnormal differential. Further testing then reveals CML, often still in chronic phase.
Diagnostic tests
Doctors combine information from the history, physical exam, blood tests, bone marrow tests, and special genetic tests to diagnose CML and tell it apart from other blood cancers. The key proof is finding the BCR-ABL1 fusion gene or the Philadelphia chromosome in blood or bone marrow cells.
Physical examination tests
Full physical examination with medical history
The doctor asks about symptoms such as fatigue, weight loss, night sweats, bleeding, and infections, and about past illnesses and exposures. They then examine the whole body, looking for signs like pallor, bruises, enlarged organs, or lymph nodes. This exam gives first clues that a blood cancer like CML may be present.Abdominal examination for spleen and liver size
During the exam, the doctor feels (palpates) and taps (percusses) the abdomen. In CML, the spleen is often enlarged and can sometimes be felt far below the left rib margin. The liver may also be enlarged. Measuring how far the spleen extends helps stage the disease and follow response to treatment over time.Skin and mucous membrane examination
The doctor closely inspects the skin, gums, and inside of the mouth. Pale color can suggest anemia, while bruises, petechiae, or bleeding gums can suggest low or abnormal platelets. Rashes or skin nodules may rarely show leukemia deposits or infections due to a weak immune system.
Manual tests (bedside hands-on examinations)
Manual palpation of lymph nodes
The doctor uses their hands to feel for enlarged lymph nodes in the neck, underarms, and groin. While marked lymph node swelling is more typical of other leukemias or lymphomas, careful node examination helps rule out other conditions and can sometimes find spread of leukemia.Manual joint examination for gout-like arthritis
Because uric acid can be high, the doctor may gently move and press joints to look for tenderness, warmth, and swelling, especially in the feet and ankles. Finding a gout-like pattern can support the suspicion of a blood cancer causing heavy cell turnover.Bedside neurologic examination
A simple neurologic exam checks muscle strength, reflexes, sensation, and balance. This may reveal signs of hyperviscosity, anemia-related weakness, or nerve problems from medicines or metabolic changes. Though not specific to CML, it helps build a full picture of the person’s health.
Lab and pathological tests
Complete blood count (CBC) with differential
A CBC measures numbers of red cells, white cells, and platelets. In CML, the total white blood cell count is usually very high, and the differential shows many granulocytes at different maturation stages. Platelets may be high or low, and anemia is common. A very abnormal CBC is often the first sign that leads to further testing.Peripheral blood smear
A smear is made by spreading a drop of blood on a glass slide and examining it under a microscope. In CML, there are many mature and immature granulocytes lined up, with relatively fewer blasts than in acute leukemia. The smear helps confirm that the high white count matches a chronic myeloproliferative pattern.Bone marrow aspiration
In this test, liquid marrow is drawn from the hip bone with a needle. The sample is examined under a microscope to see the number and types of cells. In CML, the marrow is very cellular and crowded with granulocytic precursors. This test also provides material for genetic and molecular studies.Bone marrow trephine biopsy
A small core of bone and marrow is removed to see the overall structure. Pathologists look at how full the marrow is, how cells are arranged, and whether there is fibrosis or other changes. This helps distinguish chronic from advanced phases and rules out other bone marrow diseases.Conventional cytogenetic karyotyping
Chromosomes from marrow cells are stained and studied under a microscope. In CML, the key finding is the Philadelphia chromosome, the shortened chromosome 22 created by the t(9;22) translocation. Karyotyping can also show extra chromosomal changes that may signal more advanced disease.Fluorescence in situ hybridization (FISH) for BCR-ABL1
FISH uses fluorescent probes that bind to specific DNA sequences. In suspected CML, probes for BCR and ABL1 are used. When the fusion gene is present, the probes overlap to give a fused signal. FISH can be done on blood or marrow and is more sensitive than simple karyotyping for detecting the translocation.Qualitative RT-PCR for BCR-ABL1 detection
Reverse-transcriptase PCR looks for BCR-ABL1 RNA, showing whether the fusion gene is present. Qualitative PCR answers “yes” or “no” and is very sensitive, detecting tiny amounts of leukemia cells that may be missed by other tests. It confirms the CML diagnosis at the molecular level.Quantitative real-time PCR (qPCR, IS) for BCR-ABL1 level
Quantitative PCR measures how much BCR-ABL1 transcript is present, usually on an International Scale (IS). This test is essential not only at diagnosis but also for long-term monitoring of response to tyrosine kinase inhibitor therapy, because falling levels show that treatment is working.Biochemistry panel including uric acid and LDH
Blood chemistry tests check kidney and liver function, electrolytes, uric acid, and lactate dehydrogenase (LDH). In CML, uric acid and LDH are often high due to rapid cell turnover. These tests help detect tumor lysis risk and guide supportive care before and during treatment.
Electrodiagnostic tests
Electrocardiogram (ECG)
An ECG records the heart’s electrical activity. It is not used to diagnose CML itself, but it is important when treating patients with certain tyrosine kinase inhibitors, which can affect heart rhythm. An ECG helps ensure that heart conduction is safe before and during these therapies.Nerve conduction studies and electromyography (EMG) when needed
In some cases, patients may develop nerve problems from treatment side effects, metabolic issues, or unrelated conditions. Nerve conduction tests and EMG measure how well nerves and muscles carry electrical signals. While not routine, they can be used if there is unexplained numbness, weakness, or pain.
Imaging tests
Abdominal ultrasound
Ultrasound uses sound waves to create images of the organs. It is a simple, radiation-free way to measure spleen and liver size. In CML, ultrasound can confirm and document splenomegaly and follow its improvement with treatment over time.Computed tomography (CT) scans
CT scans give detailed cross-sectional images of the body using X-rays. CT is not needed in every CML patient but may be used when there is concern about organ involvement, complications, or to rule out other causes of symptoms. It can show enlarged organs, lymph nodes, or blood clots.Chest X-ray or other targeted imaging
A chest X-ray may be done if there are respiratory symptoms, to look for infections, fluid, or enlargement of the mediastinum. Other targeted imaging (such as MRI or PET-CT) is used in special situations to evaluate complications or to look for other cancers, but it is not needed for routine CML diagnosis.
Non-pharmacological treatments (therapies and other supports)
1. Regular specialist follow-up and blood tests
Seeing a hematologist/oncologist on a regular schedule is one of the most powerful non-drug “treatments.” At each visit, the doctor checks a complete blood count, physical exam, and sometimes BCR-ABL1 levels. The purpose is to make sure the leukemia stays under control, to spot side effects early, and to adjust medicines if needed. This works because careful monitoring lets the team react quickly before problems become severe.
2. Molecular monitoring of BCR-ABL1 levels
BCR-ABL1 is measured with a special blood test called quantitative PCR. Results are often given as “international scale” percentages. The purpose is to see how deeply the leukemia is responding to treatment and whether the patient reaches milestones like “major molecular response.” If levels stop falling or rise again, doctors can change the TKI or adjust the dose. This mechanism—track the cancer signal and respond—helps prevent progression to advanced phases.
3. Patient education and adherence coaching
CML medicines usually work only if taken every day. Non-pharmacological “adherence counseling” helps patients understand why missing doses is dangerous, how to set reminders, and how to handle side effects without stopping the drug on their own. The main purpose is to keep drug levels steady in the body so BCR-ABL1 remains blocked. Good adherence is directly linked to better survival and lower risk of disease progression.
4. Psychological counseling and mental-health support
A diagnosis of leukemia can cause fear, sadness, and anxiety. Psychological support with a counselor, psychologist, or support group allows patients to talk about emotions, learn coping skills, and reduce stress. The purpose is to improve quality of life, sleep, and treatment adherence. Chronic stress can affect immune and hormonal systems; reducing stress can indirectly support the body’s resilience and the person’s ability to stay on therapy.
5. Nutritional counseling
Dietitians can design an eating plan that supports energy, muscle mass, and immunity. The purpose is to prevent malnutrition, anemia from poor diet, or excessive weight gain from inactivity. A balanced diet with enough protein, fruits, vegetables, and whole grains provides vitamins and minerals needed for blood cell production and healing. Nutrition counseling also helps avoid unsafe supplements or foods that may interact with TKIs, such as grapefruit products.
6. Infection-prevention lifestyle measures
CML and its treatments can lower normal white blood cells. Non-pharmacological infection control includes frequent handwashing, oral hygiene, avoiding close contact with people who are sick, and keeping cuts clean. The purpose is to reduce bacterial and viral infections that could cause serious illness, hospital stays, or treatment interruptions. This works by lowering the number of germs that enter the body and supporting the natural barrier defenses of skin and mucosa.
7. Vaccination (as advised by the doctor)
Inactivated vaccines (for example, flu, COVID-19, pneumococcal) are often recommended, timed around treatment. The purpose is to reduce the chance of preventable infections. Vaccines work by training the immune system to recognize germs before they cause severe disease. Live vaccines are usually avoided or carefully planned because of immune suppression; decisions must be made by a specialist.
8. Physical activity and exercise programs
Gentle, regular activity such as walking, stretching, or light strength training can fight fatigue, keep muscles strong, and support heart health. The purpose is to improve daily function and mood. Exercise improves blood flow, stimulates muscles and bones, and can reduce treatment-related tiredness. It must be adapted to each person’s blood counts and symptoms, and high-risk activities should be avoided when platelets are low.
9. Smoking cessation and alcohol moderation
Stopping smoking and limiting alcohol reduce stress on the heart, blood vessels, and liver. The purpose is to lower the risk that TKIs will cause or worsen heart disease, lung disease, or liver injury. Smoking damages blood vessels and increases clot and cancer risk; alcohol overloads the liver, where many TKIs are processed. Removing these extra burdens helps treatments stay safer and more effective.
10. Sleep and fatigue-management strategies
Many people with CML experience tiredness. Sleep hygiene (regular sleep schedule, dark quiet bedroom, limiting screens before bed) and rest breaks in the day can help. The purpose is to restore energy and improve concentration. Good sleep supports immune function, hormone balance, and mood regulation, which together can help patients manage long-term therapy more easily.
11. Social work, financial and practical support
CML care can be expensive and time-consuming. Social workers help patients apply for insurance programs, transportation help, and work or school accommodations. The purpose is to reduce financial and practical stress so that people can attend visits and continue treatment. Lower stress and better access to care often result in more stable disease control and fewer missed doses.
12. Palliative and supportive-care services
Supportive-care teams focus on symptom control—pain, itching, shortness of breath, or emotional distress—at any stage of CML, not only at end of life. The purpose is to optimize comfort and function. They use non-drug strategies (relaxation, counseling) and coordinate with the oncology team so that disease-directed therapy and comfort care work together. This improves quality of life and can even support longer survival.
Drug treatments
Tyrosine kinase inhibitors (TKIs) are the main medicines for BCR-ABL1–positive CML. Choice of drug and dose always depends on age, phase of disease, other illnesses, and side effects.
1. Imatinib (Gleevec and generics)
Imatinib is the first-generation TKI that changed CML from a deadly cancer to a chronic disease. It blocks the BCR-ABL1 tyrosine kinase and also targets c-KIT and PDGFR. A typical adult starting dose for chronic-phase CML is 400 mg once daily, but doctors adjust for disease phase and tolerance. It is taken with food and water to reduce stomach upset. Common side effects include swelling, nausea, muscle cramps, rash, and low blood counts.
2. Dasatinib (Sprycel, generics, Phyrago)
Dasatinib is a second-generation TKI that is more potent than imatinib and can overcome many imatinib-resistant BCR-ABL1 mutations. It also inhibits Src-family kinases. For chronic-phase CML, recommended adult doses are often 100 mg once daily, with higher doses in advanced phases as per label, but the exact dose is individualized by the treating physician. It can be taken with or without food. Important side effects include low blood counts, fluid around the lungs (pleural effusion), diarrhea, and bleeding risks.
3. Nilotinib (Tasigna, Danziten and other formulations)
Nilotinib is another second-generation TKI designed to bind BCR-ABL1 more tightly than imatinib. It is used as initial therapy and after imatinib failure. For chronic-phase CML, older labels used 300 mg twice daily with fasting; newer tablet formulations may allow different dosing and fewer food restrictions, so doctors follow the latest label. The drug can cause QT-interval prolongation on ECG, high blood sugar, and arterial events, so heart and metabolic monitoring is needed.
4. Bosutinib
Bosutinib is a second-generation TKI used when other TKIs are not tolerated or when the disease is resistant. It inhibits BCR-ABL1 and Src kinases. Usual adult doses for chronic-phase CML start around once daily dosing with food, but exact mg strength is chosen by the oncologist, especially if there is liver or kidney disease. Common side effects are diarrhea, nausea, liver enzyme elevation, and low blood counts. Bosutinib is especially useful after failure of imatinib, dasatinib, or nilotinib.
5. Ponatinib
Ponatinib is a third-generation TKI created to block T315I and other resistant BCR-ABL1 mutations that do not respond to earlier TKIs. It is powerful but carries higher risks of serious blood-clot and vessel-related events. Typical starting doses are decided by the specialist based on risk–benefit balance; lower doses may be used once a deep response is reached. Careful monitoring of blood pressure, cholesterol, and circulation is required.
6. Asciminib
Asciminib is a newer “allosteric” TKI that binds a different pocket (the myristoyl pocket) of BCR-ABL1 rather than the ATP site. This unique mechanism allows it to work even when some ATP-binding–site mutations are present and to be combined with other TKIs in trials. It is given as oral tablets, often twice daily, but exact dose depends on prior TKI use and mutation status. Side effects include nausea, fatigue, pancreatic enzyme elevation, and cardiovascular risks that require monitoring.
7. Hydroxyurea
Hydroxyurea is a chemotherapy tablet that slows DNA synthesis. It is often used before TKIs or at diagnosis to quickly lower very high white blood cell counts and relieve symptoms such as headache or vision changes. Doses are adjusted daily by blood counts. Once the TKI takes effect, hydroxyurea is usually stopped. Side effects include low blood counts, mouth ulcers, and darkening of skin or nails.
8. Interferon-alpha (including pegylated forms)
Interferon-alpha is an immune-modulating cytokine used less often now but still useful in special settings, such as during pregnancy when TKIs may be unsafe. It helps the immune system attack leukemia cells and slows their growth. It is usually given as injections several times per week or as a weekly pegylated form. Side effects often include flu-like symptoms, mood changes, and fatigue, so close follow-up is needed.
9. Omacetaxine mepesuccinate
Omacetaxine is a non-TKI protein-synthesis inhibitor used in some patients with chronic or accelerated CML who are resistant to multiple TKIs. Given by subcutaneous injection in cycles, it reduces BCR-ABL1–positive cells by blocking new protein production. It can cause significant low blood counts and infection risk, so it is reserved for people who cannot be managed with TKIs alone.
10. Supportive medicines (antiemetics, antibiotics, others)
Many additional drugs are used around CML treatment, such as anti-nausea medicines, antibiotics for infections, and medicines to control blood pressure or cholesterol when TKIs raise cardiovascular risk. These do not treat the leukemia directly, but they make it safer to continue TKIs. The choice and dose of each supportive drug is carefully matched to the person’s other conditions and possible interactions with TKIs.
(For website readers: there are more specific drugs and formulations, but the TKIs above are the core FDA-approved targeted therapies for BCR-ABL1–positive CML.)
Dietary molecular supplements (supportive, not cures)
Always ask the treating doctor before starting any supplement, because many products can interact with TKIs or affect the liver.
1. Vitamin D
Vitamin D supports bone health, muscle function, and immune regulation. Low levels are common in people with chronic illness. Carefully dosed vitamin D (as cholecalciferol) can correct deficiency and may improve fatigue and bone aches. It works by helping the body absorb calcium and modulating immune responses. Too much can cause high calcium and kidney problems, so blood levels must be checked.
2. Omega-3 fatty acids (fish oil)
Omega-3 fats have anti-inflammatory effects and may help with heart and blood vessel health, which is important for patients on TKIs that increase vascular risk. They are usually taken as capsules with food. Omega-3s reduce production of pro-inflammatory molecules and may improve triglyceride levels. High doses can slightly increase bleeding risk, especially with low platelets, so dosing should be modest and supervised.
3. Probiotics
Probiotics are beneficial bacteria found in some yogurts and capsules. They support gut health and may reduce antibiotic-related diarrhea. They work by stabilizing the gut microbiome and competing with harmful bacteria. In profoundly immune-suppressed patients, some doctors avoid high-dose probiotics because of rare infection risk, so decisions must be individualized.
4. Curcumin (from turmeric)
Curcumin has antioxidant and anti-inflammatory properties studied in many cancers, including leukemia, mainly in laboratory models. It may help with joint stiffness or mild inflammation. It acts by modulating cell signaling and reducing reactive oxygen species. Curcumin can affect liver enzymes and drug metabolism, so only low-to-moderate doses under medical guidance are reasonable.
5. Green tea polyphenols (EGCG)
Green tea contains catechins like EGCG with antioxidant effects. Moderate consumption as a drink may support cardiovascular and metabolic health. These molecules scavenge free radicals and may gently improve cholesterol. Concentrated extracts, however, can be harsh on the liver and interact with medications, so pills are usually avoided unless a doctor agrees.
6. Selenium
Selenium is a trace mineral used by antioxidant enzymes such as glutathione peroxidase. In small, supervised doses it may support antioxidant defenses and thyroid health. It works by helping enzymes neutralize hydrogen peroxide and lipid peroxides. Too much selenium can cause hair loss, brittle nails, and nerve problems, so supplementation should only treat a documented deficiency.
7. Zinc
Zinc is important for wound healing, taste, and immune function. Short-term supplementation can help correct deficiency caused by poor appetite or diarrhea. It serves as a co-factor for many enzymes and supports T-cell and B-cell function. Long-term high doses can lower copper and cause anemia or nerve issues, so the dose and duration must be limited.
8. Folate and vitamin B12
Folate and B12 are essential for red blood cell production and DNA synthesis. In people with low levels, careful replacement can improve anemia and fatigue. These vitamins work by supporting normal DNA replication in bone marrow cells. However, in active leukemia, supplements must be guided by the hematologist, because changing growth signals in bone marrow can affect blood counts and may mask other causes of anemia.
9. Coenzyme Q10 (CoQ10)
CoQ10 helps mitochondria make energy (ATP) and has antioxidant properties. Some people use it to help with fatigue or muscle aches. It acts in the electron transport chain and stabilizes cell membranes. It may slightly lower blood pressure or interact with blood thinners, so doses should be modest and monitored.
10. Melatonin
Melatonin is a hormone that regulates the sleep–wake cycle. Low-dose melatonin at night can improve sleep in some people receiving cancer therapy. Better sleep supports immune function and mood. Melatonin also has antioxidant and anti-inflammatory actions in experimental models. It can cause vivid dreams or morning sleepiness in some, so dose adjustments are needed.
Immunity-booster, regenerative and stem-cell related drugs
1. Filgrastim (G-CSF) and related agents
Filgrastim is a granulocyte-colony stimulating factor that boosts neutrophil production in the bone marrow. It is given as subcutaneous injections when white blood cell counts are dangerously low, especially neutrophils. The purpose is to reduce infection risk and help patients stay on leukemia treatment. It works by binding G-CSF receptors on marrow cells and stimulating their growth. Common side effects are bone pain and temporary high white counts.
2. Pegfilgrastim
Pegfilgrastim is a long-acting version of G-CSF with polyethylene glycol attached, allowing once-per-cycle dosing in some chemotherapy settings. In CML it may be used when deeper immune support is needed or when frequent injections are impractical. The mechanism is similar to filgrastim but with slower clearance. Monitoring is required to avoid extremely high white counts.
3. Erythropoiesis-stimulating agents (ESAs)
Drugs like epoetin alfa or darbepoetin can be used in selected patients with significant anemia not mainly due to active leukemia. They mimic natural erythropoietin and stimulate red blood cell production in the bone marrow. The purpose is to reduce transfusion needs and improve fatigue. They can increase clot risk, so they are used under strict guidelines and avoided when not clearly needed.
4. Thrombopoietin receptor agonists
Agents such as romiplostim or eltrombopag can increase platelet production in some marrow conditions. In CML they are rarely used, but in special situations with severe low platelets not directly due to leukemia, they may help. They activate TPO receptors on megakaryocyte precursors, pushing them to make more platelets. Risks include excessive platelet rise and possible stimulation of abnormal clones, so they are specialist-only drugs.
5. Intravenous immunoglobulin (IVIG)
IVIG is pooled antibodies from healthy donors given through a vein. It is used in certain immune-mediated low platelets or recurrent infections due to antibody deficiency. IVIG works by supplying ready-made antibodies and modulating the immune system. It is not a direct leukemia treatment but supports immunity in selected cases. Side effects can include headache, infusion reactions, and kidney stress.
6. Allogeneic hematopoietic stem-cell transplantation (as a regenerative therapy)
Although often listed under “surgery,” stem-cell transplant is also a regenerative cellular therapy. Donor stem cells are infused after intensive chemotherapy ± radiation. The new stem cells rebuild the bone marrow and can create a graft-versus-leukemia effect, where donor immune cells attack residual CML cells. It can potentially cure CML but carries high risks, including infections, graft-versus-host disease, and organ toxicity, so it is reserved for advanced or TKI-resistant cases.
Surgeries and procedures
1. Allogeneic stem-cell transplantation
This procedure involves giving high-dose chemotherapy (and sometimes radiation) to wipe out the patient’s marrow, then infusing donor stem cells through a vein, similar to a blood transfusion. It is done to try to cure CML or control very advanced disease when TKIs fail. The new immune system can attack the leukemia but also may attack normal tissues (graft-versus-host disease), so this is a high-risk, highly specialized procedure.
2. Splenectomy
Splenectomy is surgical removal of the spleen. In rare CML cases with massive, painful splenomegaly that does not respond to medical treatment, removing the spleen can relieve pain, early fullness, or low blood counts from “trapping” cells. It is done less often now because TKIs usually shrink the spleen. After splenectomy, infection risk increases, so vaccines and antibiotics become very important.
3. Leukapheresis
Leukapheresis is a procedure rather than a classic surgery. Blood is taken from one vein, white blood cells are removed by a machine, and the rest of the blood is returned. It is done in emergencies when white counts are extremely high and causing symptoms such as breathing problems or vision changes. The purpose is to quickly lower cell numbers while long-term medicines (like TKIs) start to work.
4. Central venous catheter or port placement
Some people need a long-term central line or port for blood draws and infusions. A surgeon or interventional radiologist inserts a small flexible tube into a large vein, often under local anesthesia with light sedation. This is done to reduce repeated needle sticks and allow safer delivery of some treatments or transfusions. Risks include infection and clotting, so careful care of the line is important.
5. Bone marrow biopsy and aspiration
This is a minor but invasive procedure: a needle is inserted into the hip bone to take bone marrow samples. It is done to confirm diagnosis, assess phase of disease, or check for additional chromosomal changes. Local anesthesia reduces pain, and the procedure is usually quick. The purpose is to guide treatment choices and check for progression to accelerated or blast phase.
Preventions
Take TKIs exactly as prescribed – Do not skip or change doses without your doctor. This keeps BCR-ABL1 blocked and helps prevent progression to advanced phases.
Keep all follow-up appointments and lab tests – Regular PCR and blood counts show how well treatment is working and catch problems early.
Report side effects early – Tell your doctor about swelling, shortness of breath, chest pain, rashes, or severe fatigue. Adjusting dose or switching TKIs can prevent serious harm.
Protect heart and blood vessels – Control blood pressure, cholesterol, diabetes, and weight; stop smoking; exercise as allowed. This lowers risk from TKIs that may increase vascular problems.
Prevent infections – Practice hand hygiene, keep vaccines up to date, and avoid close contact with people who have flu or other contagious illnesses.
Avoid unsafe supplements and over-the-counter drugs – Grapefruit, St John’s wort, and some herbal products can dangerously change TKI levels; always ask your doctor first.
Protect liver and kidneys – Limit alcohol, avoid unnecessary painkillers like high-dose NSAIDs, and stay well hydrated unless you are on a fluid restriction.
Maintain good oral care – Regular tooth-brushing and dentist visits lower the risk of mouth infections, especially when white cells are low.
Use sun protection – Some TKIs may increase skin sensitivity; sunscreen and protective clothing help prevent rashes and skin damage.
Plan pregnancy carefully – People who may become pregnant should talk with their doctor before conception, because TKIs can harm a developing baby and special plans are needed.
When to see doctors
You should see your doctor urgently or go to emergency care (according to local advice) if:
You have fever, chills, or signs of infection (sore throat, burning when urinating, cough with mucus).
You notice unusual bleeding or bruising, nosebleeds that do not stop, or blood in urine or stool.
You feel short of breath, have chest pain, or sudden swelling in a leg, which could signal fluid or clot problems.
You develop severe headaches, vision changes, or confusion, especially with very high white counts.
You have strong abdominal pain or rapid enlargement of the spleen area (left upper abdomen).
You get severe rash, peeling skin, or swelling of lips and face, which may mean an allergic reaction.
You have persistent vomiting, severe diarrhea, or cannot keep medicines down.
You notice very fast weight gain, swelling, or difficulty breathing when lying down, which may signal fluid retention.
Regular planned visits should also be kept even when you feel well, because CML monitoring relies heavily on lab tests and molecular results.
What to eat and what to avoid
What to eat (general guidance, not a strict diet plan)
Plenty of fruits and vegetables – Aim for a variety of colors to provide vitamins, minerals, and antioxidants. Wash them well to reduce infection risk from germs or pesticides.
Lean proteins – Fish, poultry, eggs, tofu, and legumes support muscle maintenance and blood cell production.
Whole grains – Brown rice, oats, and whole-grain bread provide energy and fiber to prevent constipation.
Healthy fats – Nuts, seeds, olive oil, and fatty fish give essential fatty acids that support heart and brain health.
Safe fluids – Clean water, herbal teas, and clear broths help maintain hydration and kidney function unless your doctor limits fluids.
What to avoid or limit
Grapefruit and Seville orange products – These can raise blood levels of some TKIs and increase side effects, so they are usually avoided.
Unpasteurized foods and raw meats or eggs – These increase infection risk, especially if white cells are low.
Large amounts of alcohol – Alcohol stresses the liver, where TKIs are metabolized, and increases bleeding and heart risks.
Very salty or heavily processed foods – These can worsen blood pressure and heart strain, important in patients on TKIs with vascular risks.
Unapproved herbal products or high-dose supplements – Many interact with liver enzymes and drug transporters, changing TKI levels in dangerous ways. Always discuss with the oncology team.
Frequently asked questions (FAQs)
1. Is CML, BCR-ABL1 positive, curable?
With TKIs, many people achieve deep, long-lasting responses and live a near-normal life span. Some can even stop treatment under strict rules called “treatment-free remission.” A transplant can sometimes cure CML but is high risk. For many, CML is managed as a chronic, controllable condition.
2. How long do I need to take TKIs?
Most people take TKIs for years. Stopping is only considered after a deep molecular response is stable for a long time and strict criteria are met. Even then, very close PCR monitoring is required, and many people restart treatment if levels rise. Your doctor decides if stopping is safe for you.
3. What happens if I miss a dose?
Missing doses can lower drug levels and give leukemia cells a chance to grow. If you forget a dose, follow your doctor’s written instructions (often take it when remembered unless it is close to the next dose). Do not double dose without guidance. Try to use reminders so it does not happen often.
4. Can CML turn into a more aggressive leukemia?
Yes. Without good control, CML can progress from chronic phase to accelerated or blast phase, which are more like acute leukemia. Regular monitoring and correct use of TKIs greatly reduce this risk. Rising BCR-ABL1 levels or new symptoms are warning signs that the doctor will check carefully.
5. Can I work or go to school while on treatment?
Many people with well-controlled CML continue normal work or study with some adjustments. Fatigue, clinic visits, and side effects may require flexibility. Work with your healthcare team and employer or teachers to plan a schedule that fits your energy and appointment needs.
6. Can I get pregnant if I have CML?
Pregnancy is possible but must be carefully planned. Many TKIs are not safe for the fetus, so doctors may change or pause medicines and watch closely. Both partners should discuss family plans with the hematologist and an obstetrician experienced in high-risk pregnancies before trying to conceive.
7. Are TKIs chemotherapy?
TKIs are often called targeted therapy rather than classic chemotherapy. They block a specific abnormal protein instead of damaging all rapidly dividing cells. Side effects can still be serious, but they are usually different from traditional chemo.
8. Will I lose my hair?
Most TKIs for CML do not cause complete hair loss like some chemotherapy drugs. Some people notice mild thinning or texture changes, while others see little change. Severe hair loss is uncommon with standard CML TKIs.
9. Do I need a special “cancer diet”?
There is no single CML diet. Healthy eating with enough calories, protein, and micronutrients is usually most important. Your doctor or dietitian may suggest extra precautions when blood counts are very low or if you have other conditions such as diabetes or heart disease.
10. Can I get vaccinated?
Most inactivated vaccines (like flu and COVID-19 shots) are recommended. Live vaccines may be delayed or avoided depending on your immune status. Always ask your hematologist before any vaccine so timing and type are safe with your treatment.
11. Are herbal or “natural” treatments safe instead of TKIs?
No. There is no reliable evidence that herbs or alternative therapies can control CML on their own. Stopping TKIs to use unproven methods can lead to severe progression. Some herbs also interact dangerously with TKIs. Use complementary methods only alongside, not instead of, standard care and with your doctor’s approval.
12. Why do I still feel tired even when my leukemia is controlled?
Fatigue can come from anemia, treatment side effects, stress, sleep problems, or other illnesses like thyroid or heart disease. Your doctor can check for treatable causes. Gentle exercise, good sleep habits, and counseling often help.
13. Can teenagers or young adults get CML?
Yes, CML can occur at any age, though it is more common in adults. Treatment principles are similar, but growth, fertility, schooling, and long-term side effects need extra attention. Pediatric or adolescent-and-young-adult oncology specialists are best placed to guide care.
14. Is CML contagious?
No. CML is not an infection and cannot be passed from one person to another by touch, food, or air. It starts from changes inside bone marrow cells and is not spread like a virus.
15. Where can I find reliable information?
Trusted sources include national cancer organizations, leukemia foundations, and official drug-information sites from regulatory agencies. These sources explain treatment options, side effects, and support services in clear language. Always compare online information with guidance from your own medical team.
Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.
The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members
Last Updated: January 25, 2025.
