BCR-ABL positive chronic myelogenous leukemia (CML) is a blood cancer that starts in the bone marrow, where new blood cells are made. In CML, a piece of chromosome 9 and a piece of chromosome 22 swap places, creating the Philadelphia chromosome and a fusion gene called BCR-ABL1. This fusion gene makes an abnormal protein (BCR-ABL) that is always “switched on,” telling stem cells to make too many abnormal white blood cells that do not die when they should. Over time, these cells crowd out normal blood cells and can move from a chronic phase to more aggressive accelerated or blast phases if not controlled. Modern tyrosine kinase inhibitor (TKI) drugs block BCR-ABL and have turned CML into a long-term, often very well-controlled disease for many people.
BCR-ABL positive chronic myelogenous leukaemia (CML) is a slow-growing blood cancer. In this disease, the bone marrow makes too many white blood cells called myeloid cells. These cells are abnormal and do not work properly. They slowly crowd out normal red blood cells, normal white blood cells, and platelets.
The word “BCR-ABL positive” means that the leukaemia cells have a special broken gene called the BCR-ABL1 fusion gene. This fusion gene comes from a swap of genetic material between chromosomes 9 and 22, called the Philadelphia chromosome. The BCR-ABL1 gene makes a protein that is “always on” and tells the leukaemia cells to grow and divide all the time.
CML usually starts slowly. Many people feel well at first and the disease is sometimes found by chance on a routine blood test that shows a very high white cell count. If it is not treated, CML can move from a quiet “chronic phase” to more serious “accelerated” and “blast” phases, which behave more like an acute leukaemia.
Other names
Doctors and books may use several different names for the same disease. All of these refer to BCR-ABL positive chronic myelogenous leukaemia:
Chronic myeloid leukaemia (CML)
Chronic myelogenous leukaemia (older spelling)
BCR-ABL1–positive chronic myeloid leukaemia
Philadelphia chromosome–positive CML (Ph+ CML)
BCR::ABL1-positive myeloproliferative neoplasm (WHO term)
These names all point to the same key idea: a chronic myeloproliferative cancer defined by the BCR-ABL1 fusion gene and usually by the Philadelphia chromosome.
Types
CML is usually described by phases, which show how advanced the disease is:
Chronic phase CML – This is the first and most common phase. Most people are diagnosed here. There are many leukaemia cells, but they are still fairly mature, and symptoms can be mild or absent. Treatment works best in this phase.
Accelerated phase CML – In this phase, leukaemia cells grow faster and become more abnormal. Blood counts are more disturbed, and symptoms such as tiredness and spleen enlargement often worsen.
Blast phase (blast crisis) CML – In this final phase, many very immature cells (blasts) appear in the blood and bone marrow. It behaves like an acute leukaemia and is much harder to treat.
Doctors may also talk about molecular subtypes based on the exact kind of BCR-ABL1 protein:
p210 BCR-ABL1 – the typical and most common form in CML.
p190 or p230 BCR-ABL1 – less common forms, sometimes linked to unusual features.
Causes and risk factors
For most people with BCR-ABL positive CML, there is no clear single cause. The disease usually starts from a random genetic change in one stem cell in the bone marrow. However, some factors are known or suspected to increase risk.
Random DNA change in a bone marrow stem cell
The main cause is a chance mistake when a stem cell in the bone marrow copies its DNA. This mistake creates the Philadelphia chromosome and the BCR-ABL1 fusion gene. It is not usually inherited from parents and often happens without any obvious trigger.High-dose ionising radiation
People exposed to very high doses of radiation (for example, atomic bomb or nuclear accident survivors, or some past medical exposures) have a higher risk of CML. Radiation can damage DNA and make chromosome breakages that form the BCR-ABL1 fusion.Previous therapeutic radiation
Radiation therapy for other cancers or conditions slightly increases the risk of CML later in life. The radiation used for treatment can also cause DNA damage in bone marrow stem cells.Occupational exposure to benzene
Long-term exposure to benzene, a chemical in some industries (oil, rubber, chemical plants), is a known risk factor for some leukaemias and is suspected in CML as well. Benzene damages bone marrow DNA over many years.Benzene in cigarette smoke and petrol fumes
Cigarette smoke and petrol exhaust contain benzene. Long-term breathing of these fumes may add to total benzene exposure and slightly increase leukaemia risk, including possible CML.Older age
CML is much more common in middle-aged and older adults than in young people. As we age, bone marrow cells have had more time to collect DNA damage, which may lead to the BCR-ABL1 fusion in a stem cell.Male sex
CML occurs a bit more often in men than in women. The exact reason is not clear. It may relate to differences in exposures (such as smoking or work) or biological differences between sexes.Family history of CML (rare)
Most people with CML do not have a family history. However, rare reports show more CML or BCR-ABL1 in first-degree relatives, which suggests some families may have a higher tendency for DNA damage or chromosome breaks.Other inherited DNA repair problems
People born with syndromes that reduce normal DNA repair (for example, some inherited bone marrow failure syndromes) may, in theory, have a higher chance of leukaemia, including CML, because their cells cannot fix DNA mistakes well.Previous chemotherapy for other cancers
Some chemotherapy drugs (especially older alkylating agents and topoisomerase-II inhibitors) can damage bone marrow DNA. This may rarely lead to therapy-related CML or other leukaemias years after treatment.Obesity
Several studies suggest that obesity is a risk factor for leukaemia. Extra body fat can cause long-term inflammation and hormone changes that may increase the chance of DNA damage and abnormal cell growth in the bone marrow.Smoking
Research shows mixed results, but some studies suggest that smoking, which carries many carcinogens including benzene, may slightly raise the risk of myeloid leukaemias, including CML.Long-term exposure to other industrial solvents
Strong industrial chemicals and solvents (besides benzene) used in some workplaces may damage bone marrow over time. Evidence is weaker than for benzene, but these exposures are still watched as possible leukaemia risks.Chronic immune stimulation and inflammation
Long-lasting inflammation in the body may create more reactive oxygen species, which can harm DNA. This constant low-grade damage may increase the risk that a stem cell develops the BCR-ABL1 fusion.General background environmental radiation
Everyone is exposed to low levels of natural background radiation (from the sun, soil, and buildings). This small risk cannot be avoided completely, but it is usually very low. Rarely, it may take part in DNA damage over a lifetime.Urban air pollution
Air pollution contains many tiny particles and chemicals, some of which can damage DNA. Studies in leukaemia suggest that long-term exposure to polluted air might slightly increase leukaemia risk, though direct data for CML are limited.Previous bone marrow stress or injury
Radiation, toxins, severe infections, or other injuries to bone marrow may force stem cells to divide more to repair the damage. More cell divisions mean more chances for DNA copying errors, including the BCR-ABL1 fusion.Chance combination of many small risks
For many people, CML may appear because of several small risk factors happening together, such as age, mild environmental exposures, and random DNA errors. Often no single “big” cause can be found.Unknown or yet-to-be-discovered risk factors
Scientists believe there are still unknown factors that contribute to CML risk, because most people with known risk factors never get CML and many patients have no clear risk factor at all.The BCR-ABL1 fusion itself as the driving cause
Once the BCR-ABL1 fusion appears in a stem cell, it becomes the key driver of CML. The BCR-ABL1 protein is a tyrosine kinase that sends constant “grow and survive” signals to myeloid cells, causing long-term overgrowth and leading to leukaemia.
Symptoms
Not everyone with CML has symptoms at diagnosis. Many symptoms are general and can be caused by many other illnesses, so they do not prove CML by themselves.
Tiredness and weakness
Many people with CML feel very tired or weak. This is often due to anaemia, which happens when leukaemia cells crowd out normal red blood cells so the body carries less oxygen.Shortness of breath
Because of anaemia and the extra workload on the heart and lungs, some people feel breathless, especially when walking or climbing stairs. They may feel they “cannot catch their breath” as easily as before.Unexplained weight loss
People may lose weight without trying. This can happen because the body uses extra energy fighting the cancer, and because loss of appetite and early fullness can reduce food intake.Loss of appetite and feeling full quickly
An enlarged spleen can press on the stomach. People may feel full after only a small meal or may lose interest in eating. This often goes together with weight loss.Night sweats
Some people wake up soaked in sweat, even when the room is cool. Night sweats may be related to fever, high white cell counts, or the body’s response to the leukaemia.Fever
A low-grade or sometimes higher fever may appear. It can be due to infections, because abnormal white cells do not fight germs well, or due to the cancer itself.Pain or fullness under the left ribs
The spleen often becomes enlarged in CML. This can cause a feeling of heaviness, fullness, or dull pain under the left side of the rib cage. Sometimes the spleen can be felt as a firm mass.General tummy (abdominal) discomfort
As the spleen and sometimes the liver grow larger, people may feel vague discomfort, bloating, or pressure in the upper abdomen. This may go with early satiety and weight loss.Bone or joint pain
Leukaemia cells collect in the bone marrow and can stretch the covering of the bone or irritate nearby joints, causing pain in the bones or joints, especially at night or with movement.Easy bruising and bleeding
When platelets are low or abnormal, people may bruise easily, have nosebleeds, bleeding gums, or heavier menstrual periods. In some CML patients, platelets can also be too high, which can lead to abnormal clotting as well as bleeding.Frequent infections
Even though white blood cell counts are very high, many of the cells are abnormal and do not fight infection well. This can lead to repeated or long-lasting infections, such as chest infections or skin infections.Pale skin (pallor)
Anaemia from low red blood cell counts can make the skin look paler than usual, especially on the face, lips, and nail beds. People often notice they look “washed out.”General feeling of being unwell
Many people describe a vague feeling of not being themselves, with low energy, mild aches, or feeling “run down” for a long time before diagnosis.Itching or skin discomfort
Some patients report itchy skin or a crawling feeling, especially at night. The exact cause is unclear but may relate to cytokines (chemical signals) released by leukaemia cells.Visual problems (rare)
Very high white cell counts can thicken the blood and, in rare cases, cause small bleeds or reduced blood flow in the eye, leading to blurred vision or spots. This is more common in advanced phases.
Diagnostic tests
Doctors use a group of tests together to diagnose BCR-ABL positive CML. No single test is enough by itself. The key is to show high myeloid cells and prove the BCR-ABL1 fusion gene in blood or bone marrow.
Physical exam tests
General physical examination
The doctor checks overall health: weight, temperature, heart rate, breathing, blood pressure, and looks for signs such as pallor, bruises, or infections. This gives clues that blood counts may be abnormal and that a leukaemia like CML might be present.Abdominal exam for spleen size
The doctor carefully feels (palpates) the abdomen, especially under the left ribs, to see if the spleen is enlarged or tender. A large spleen is very common in CML and is an important physical sign.Liver examination
The liver may also be enlarged. The doctor feels under the right ribs and may tap (percuss) the liver edge. Liver enlargement can occur because abnormal blood cells collect there in CML.Lymph node examination
The doctor feels the neck, armpits, and groin for enlarged lymph nodes. Swollen nodes are less common in CML than in some other leukaemias, but they can appear, especially in advanced phases.
Manual tests (simple bedside tests using hands and basic tools)
Manual spleen percussion test
Gentle tapping over the lower left chest and upper abdomen can help detect spleen enlargement, even when it cannot be easily felt. This is a simple bedside method to support suspicion of CML when combined with blood tests.Manual assessment of bruising and skin spots
The doctor examines the skin carefully for bruises, tiny red spots (petechiae), or bleeding under the skin. This manual inspection helps show problems with platelets that can occur in CML.Simple performance test (walking test)
The doctor may ask the patient to walk or climb a few steps and report breathlessness or fatigue. This informal manual test helps to judge how much anaemia or overall weakness is affecting daily life.Manual neurological check (strength and sensation)
A quick check of hand-grip strength, leg strength, and basic sensation can show if there are any nervous system problems, especially in advanced disease or if there are worries about bone lesions or high blood thickness.
Lab and pathological tests
Complete blood count (CBC) with differential
This is a key first test. A small blood sample is run through a machine that counts red cells, white cells, platelets, and types of white cells. In CML, the white count is usually very high, with many myeloid cells at different stages of maturity.Peripheral blood smear
A thin layer of blood is spread on a glass slide, stained, and viewed under a microscope. The doctor can see many different immature and mature myeloid cells typical of CML and can look for blasts and abnormal shapes.Bone marrow aspiration
A needle is used to draw liquid bone marrow, usually from the hip bone. The sample is examined for increased myeloid cells, blasts, and other features of CML. It also provides cells for genetic tests.Bone marrow biopsy (trephine)
A tiny core of bone and marrow is taken with a special needle. This shows the structure of the marrow, how crowded it is, and patterns of cell growth. It helps confirm that CML is a chronic myeloproliferative neoplasm.Conventional cytogenetic testing (karyotyping) for Philadelphia chromosome
This test grows marrow cells in the lab and looks at their chromosomes. In CML, most cells have the Philadelphia chromosome, the swapped piece between chromosomes 9 and 22 that creates BCR-ABL1. This is a central diagnostic proof.FISH (fluorescence in situ hybridisation) for BCR-ABL1
FISH uses coloured probes that stick to BCR and ABL1 genes on cells. Under a special microscope, doctors can see if the genes are fused. FISH can detect the fusion even when standard chromosome studies are difficult.Quantitative RT-PCR for BCR-ABL1 transcripts
This highly sensitive molecular test measures the amount of BCR-ABL1 RNA in blood or marrow. It confirms the diagnosis and provides a baseline number for later monitoring. Results are often reported on an international scale (IS).Baseline biochemistry blood tests
Blood chemistry tests (liver function, kidney function, uric acid, electrolytes) do not diagnose CML by themselves, but they show how well organs are working and help doctors choose safe treatments and watch for tumour lysis and other complications.Additional mutation or cytogenetic tests (in some cases)
In certain patients, extra tests look for other chromosome changes or gene mutations that can affect prognosis or treatment response. These tests help refine risk groups and guide therapy choices.
Electrodiagnostic tests
Electrocardiogram (ECG)
An ECG records the heart’s electrical activity using skin electrodes. It does not diagnose CML, but it is important before and during some targeted drugs (like certain tyrosine kinase inhibitors) that can affect heart rhythm.Echocardiogram (heart ultrasound with electronic probes)
An echocardiogram uses ultrasound linked to an electronic machine to assess the heart’s pumping and valves. In CML, it may be used to check heart function before intensive treatment or transplant.
Imaging tests
Abdominal ultrasound, CT, or MRI
Imaging of the abdomen is used to measure the size of the spleen and liver and to look for other organ involvement. Ultrasound is often enough; CT or MRI may be used for more detail, especially in complex or advanced cases. These imaging tests support the diagnosis and follow-up but do not replace genetic tests.
Non-pharmacological treatments
1. Patient education and shared decision-making
Clear education about what BCR-ABL CML is, how TKIs work, and why regular blood tests are needed helps people feel less afraid and more in control. When patients understand goals like “deep molecular response” and the risk of progression, they are more likely to take medicines correctly and attend follow-up. Doctors, nurses and pharmacists should explain in simple language, use written leaflets, and check understanding. This shared approach supports better long-term outcomes because CML care is usually lifelong.
2. Adherence counselling for TKI tablets
TKIs only work well if they are taken daily exactly as prescribed. Missing doses or stopping without medical advice can allow BCR-ABL activity to rise and increase the risk of losing response or progressing to advanced phases. Simple tools like phone alarms, pill boxes, and daily routines tied to meals can improve adherence. Regular honest discussions about side effects and barriers help patients stay on therapy safely.
3. Infection-prevention hygiene
Because CML and its treatments can lower white blood cells, infection prevention is very important. Simple steps such as frequent hand-washing, using alcohol hand rub outside the home, avoiding close contact with people who are clearly unwell, and careful skin and oral care can lower infection risk. Patients are often taught to check their temperature and call the clinic if fever appears, rather than self-treating with paracetamol. These habits help catch infections early, when they are easier and safer to treat.
4. Vaccination planning
Non-live vaccines (such as inactivated influenza, COVID-19, and pneumococcal vaccines) are usually recommended to lower the risk of serious infections in people with blood cancers. Live vaccines are generally avoided while a person is immunocompromised because weakened germs in the vaccine could still cause disease. The exact timing depends on blood counts, treatment intensity, and local guidelines. Discussing a full vaccination plan with the haematology team is a key non-drug way to improve safety.
5. Healthy, balanced diet
A balanced diet rich in vegetables, fruits, whole grains, lean protein and healthy fats helps support overall strength, wound-healing and immune function. During treatment some people lose appetite, feel sick, or notice taste changes, so small, frequent meals and nutrient-dense drinks may be easier than large meals. There is no special “CML cure diet,” but general cancer-nutrition advice focuses on enough calories and protein, plus safe food handling. Dietitians can adjust plans for weight loss, diabetes, kidney disease or other problems.
6. Physical activity and gentle exercise
Regular gentle physical activity such as walking, yoga, stretching or light cycling can improve energy, sleep, mood and muscle strength. Even on treatment days, short walks or simple movements around the home can prevent stiffness and de-conditioning. People should avoid over-exertion when very anaemic or breathless, but staying as active as safely possible is encouraged. Exercise programmes can be adapted depending on age, fitness, and treatment phase.
7. Smoking cessation
Smoking increases general cancer risks and heart and blood vessel problems. Many TKIs, such as nilotinib and ponatinib, can also affect blood vessels, so smoking adds extra risk. Stopping smoking improves lung and heart health, may lower complications, and supports long-term survival in cancer survivors. Nicotine replacement, counselling, and structured stop-smoking services greatly increase success.
8. Limiting alcohol intake
Heavy alcohol use can damage the liver, which is important for breaking down TKIs and other cancer drugs. Alcohol also worsens fatigue, sleep, mood, and can irritate the stomach, making nausea worse. Most guidelines suggest either avoiding alcohol or keeping it to low amounts and never binge drinking. People with abnormal liver tests or on hepatotoxic drugs are usually advised to avoid alcohol completely.
9. Stress management and psychological support
Living with a long-term cancer such as CML can cause ongoing worry, sadness, or fear of relapse. Emotional support from counsellors, psychologists, social workers, peer groups or online communities can reduce anxiety and depression. Simple techniques like breathing exercises, mindfulness, journaling, and relaxation apps may also help. Good mental health supports better treatment adherence and improves quality of life.
10. Sleep hygiene and fatigue management
Many people on TKIs feel tired even when blood counts are good. Regular sleep routines, a calm bedroom, avoiding caffeine late in the day, and short daytime naps rather than long ones can improve energy. Planning the day with priority tasks in the morning and rest breaks in the afternoon can make fatigue more manageable. If fatigue is severe or suddenly worse, doctors will check for anaemia, thyroid problems or depression.
11. Safe food handling and “neutropenic-style” precautions when counts are low
When white cell counts are very low, simple germs in food can cause serious infections. Many centres advise careful washing of fruit and vegetables, thorough cooking of meat and eggs, and avoiding unpasteurised dairy, raw seafood, and buffet foods kept at room temperature. These rules are usually relaxed as counts recover. Individual centres vary, so local written advice is important.
12. Fall prevention and bone health
Anaemia, muscle weakness, neuropathy or dizziness from treatment can increase the chance of falls. Simple changes such as removing loose rugs, using handrails, good lighting, and supportive shoes lower risk. Weight-bearing exercise, vitamin D and calcium (if needed), and checking bone density in high-risk patients support bone health. Preventing fractures and head injury is especially important if platelets are low.
13. Sun and skin care
Some TKIs and other cancer drugs can make the skin more sensitive to sunlight. Using sunscreen, protective clothing, and avoiding intense midday sun reduces risk of burns and skin damage. Gentle moisturisers help dry or itchy skin. Patients should report new rashes or skin changes because they may be drug-related.
14. Fertility and family-planning counselling
CML often affects people in their working and child-bearing years. TKIs can harm an unborn baby, and pregnancy planning must be coordinated with the haematology team. Counselling covers contraception while on TKIs, sperm or egg preservation before intensive therapy, and safe times to stop or switch drugs if pregnancy is desired. This planning prevents unplanned exposure during pregnancy and supports family goals.
15. Workplace and school adjustments
Fatigue, frequent clinic visits, and infection risk can interfere with work or study. Flexible hours, remote work or schooling, and less physically demanding tasks help people continue their roles. Occupational health teams can help design reasonable adjustments and provide letters for employers or schools. Maintaining social and intellectual activity is good for mental health and identity.
16. Avoiding harmful chemical exposures (e.g., benzene, solvents)
Exposure to benzene and some other industrial chemicals is a known risk factor for some leukaemias, and may also influence CML risk. Avoiding or reducing contact with petrol fumes, strong solvents, and poorly ventilated chemical environments is sensible, especially for people already living with a blood cancer. Using protective equipment and ventilation at work reduces ongoing exposure.
17. Financial and social-work support
CML treatment is long-term and can create costs for travel, tests, and time off work. Social workers and patient-support organisations can help with insurance questions, benefits applications, and access to patient-assistance programmes for expensive TKIs. Reducing financial stress can improve adherence and mental health.
18. Peer support and patient groups
Meeting or talking online with other people who have CML allows sharing of practical tips and emotional experiences. Hearing long-term success stories can give realistic hope and motivation to keep taking treatment. Many national cancer charities host helplines, forums and support groups specifically for blood cancers or CML.
19. Palliative and symptom-control services when needed
Palliative care is not only for end-of-life. Specialist teams can help with pain, severe fatigue, nausea, sleep, and emotional distress at any stage. Early palliative input improves quality of life and can even improve survival in some cancers. The focus is on comfort, communication and what matters most to the person.
20. Long-term survivorship care plans
Because many people now live decades with CML on TKIs, survivorship plans are important. These plans summarise diagnosis, treatments, drug doses, side effects to monitor (such as vascular disease or metabolic changes), and recommended schedules for blood tests and other checks. A written plan shared with the family doctor helps coordinate care beyond the cancer centre.
Drug treatments
Safety note: All drugs below are prescription-only and must be used under specialist supervision. Dose examples are general from labels or reviews and are not individual medical advice.
1. Imatinib (Gleevec)
Imatinib is the first TKI that transformed CML care. It blocks the BCR-ABL tyrosine kinase and stops abnormal signals that drive leukaemic cell growth. In chronic-phase CML, a common adult dose is around 400 mg by mouth once daily, with higher doses in some settings, adjusted for side effects and response. Major side effects include fluid retention, nausea, muscle cramps, rash, low blood counts and liver enzyme changes. Imatinib is now often used when newer TKIs are not suitable or for patients with lower-risk disease or comorbidities.
2. Dasatinib (Sprycel / Phyrago)
Dasatinib is a second-generation TKI that also blocks BCR-ABL but is more potent than imatinib. For chronic-phase CML, a typical labelled starting dose in adults is 100 mg once daily, with other schedules in advanced phases, always adjusted for tolerance and blood counts. Important side effects include low blood counts, fluid around the lungs (pleural effusion), bleeding risk, diarrhoea and liver changes. Dasatinib is often used when there is resistance or intolerance to imatinib, or as first-line therapy in some guidelines.
3. Nilotinib (Tasigna)
Nilotinib is another second-generation TKI used in newly diagnosed chronic-phase CML and in some resistant cases. It is usually taken twice daily on an empty stomach, because food and grapefruit juice raise drug levels and can increase side-effect risk. Key toxicities include QT-interval prolongation on ECG, metabolic changes (high blood sugar, cholesterol), liver and pancreatic enzyme rises, and arterial vascular events. Careful ECG and metabolic monitoring is needed, and patients are told strictly to avoid grapefruit and many interacting drugs.
4. Bosutinib (Bosulif)
Bosutinib is a TKI that targets BCR-ABL and other kinases and is approved for newly diagnosed chronic-phase CML and for patients resistant or intolerant to earlier TKIs. A typical adult dose is 400–500 mg once daily with food, adjusted for kidney and liver function and side effects. Common toxicities include diarrhoea, nausea, vomiting, liver enzyme elevation and low blood counts. Patients are asked to avoid grapefruit and other strong CYP3A4 inhibitors because they can greatly increase bosutinib levels.
5. Asciminib (Scemblix)
Asciminib is a newer “STAMP” inhibitor that binds a special myristoyl pocket of ABL rather than the traditional ATP site. It is approved for adults with chronic-phase CML previously treated with at least two TKIs, and more recently for newly diagnosed chronic-phase CML. It is taken by mouth at doses defined in the label, with schedules such as 40 mg twice daily or 80 mg once daily depending on indication. Side effects include low blood counts, pancreatic enzyme elevations, liver changes and some cardiovascular risks, so regular monitoring is required.
6. Ponatinib (Iclusig)
Ponatinib is a third-generation TKI designed to work against many resistance mutations, especially T315I, which is resistant to earlier TKIs. It is used in adults with CML in any phase when no other TKI is indicated or when T315I is present. Doses vary and can be reduced to balance efficacy and toxicity; arterial thrombosis, hypertension, heart failure and pancreatitis are important risks, so cardiovascular risk factors must be managed aggressively. It is often reserved for high-risk, resistant disease under expert supervision.
7. Omacetaxine mepesuccinate (Synribo)
Omacetaxine is not a TKI; it blocks protein synthesis at the ribosome and is used in adults with chronic or accelerated-phase CML who are resistant or intolerant to at least two TKIs. It is given as a subcutaneous injection in induction and maintenance cycles, with dosing such as 1.25 mg/m² twice daily for defined days of a 28-day cycle, adjusted based on blood counts and response. Side effects include myelosuppression, infections, bleeding, hyperglycaemia and liver test abnormalities. It is an important option when TKIs no longer work or cannot be used.
8. Hydroxyurea (Hydrea)
Hydroxyurea is an older oral chemotherapy used mainly to quickly lower very high white cell and platelet counts at diagnosis or in emergencies before TKIs start. Typical dosing is weight-based (for example, around 15 mg/kg/day) and is adjusted to avoid severe myelosuppression. Side effects include low blood counts, mouth ulcers, skin changes and long-term risk of secondary cancers with prolonged use. Once TKIs control the disease, hydroxyurea is usually stopped.
9. Interferon-alpha (including pegylated forms)
Before TKIs, interferon-alpha was a main CML treatment; today it is sometimes used in special situations, such as during pregnancy when TKIs must be avoided or in combination/transition strategies. It works by stimulating the immune system and directly slowing leukaemic cell growth. Side effects often include flu-like symptoms, fatigue, mood changes and thyroid dysfunction, so careful monitoring is needed. Its role is now limited but still important in selected patients.
10. Cytarabine (Ara-C)
Cytarabine is a backbone chemotherapy drug used mainly in blast-phase CML, when the disease behaves like acute leukaemia. It interferes with DNA synthesis and kills rapidly dividing cells. Doses and schedules vary widely, from low doses to high-dose protocols, always in specialist centres. Side effects include profound myelosuppression, infection risk, mouth sores, hair loss and organ toxicity, so it is combined with strong supportive care.
11. Cyclophosphamide
Cyclophosphamide is an alkylating chemotherapy sometimes used in combination regimens for blast-phase CML or for transplant conditioning. It damages DNA and prevents cancer cells from dividing. Side effects include low blood counts, nausea, hair loss, bladder irritation and infertility risk. Because of these toxicities, it is used only in carefully planned protocols with preventive measures such as hydration and bladder protection.
12. Vincristine
Vincristine is a vinca alkaloid often included in regimens for lymphoid-blast crisis of CML, treating it similarly to acute lymphoblastic leukaemia. It disrupts microtubules, blocking cell division. Common side effects include peripheral neuropathy (numbness, tingling, weakness), constipation and hair loss; it can also affect blood counts when combined with other drugs. Dosing is carefully limited to reduce nerve damage.
13. Corticosteroids (e.g., prednisone, dexamethasone)
Steroids are used with chemotherapy in lymphoid blast crisis and to treat some drug-related complications such as severe allergic reactions or autoimmune phenomena. They reduce inflammation, shrink lymphoid masses, and can briefly improve appetite and energy. Long-term use can cause weight gain, diabetes, mood changes, bone thinning and increased infection risk, so they are usually given in short courses.
14. Allopurinol / rasburicase (tumour lysis support)
When starting intensive treatment or rapidly shrinking a very high white cell count, dead cancer cells can release uric acid and electrolytes, causing tumour lysis syndrome. Allopurinol or rasburicase are given with fluids to reduce uric acid levels and protect the kidneys. They do not treat CML directly but make cytoreduction safer. Monitoring blood chemistry closely helps detect tumour lysis early.
15. Broad-spectrum antibiotics
When CML treatment causes neutropenia and a patient develops fever, broad-spectrum intravenous antibiotics are started quickly. These drugs treat life-threatening bacterial infections while the immune system is weak. Choices depend on local resistance patterns and individual allergies. Preventive (prophylactic) antibiotics are sometimes used in very high-risk patients.
16. Antifungal drugs (e.g., fluconazole, posaconazole)
Antifungals prevent or treat fungal infections, which can be serious in people with prolonged neutropenia or prior transplants. They may be given by mouth or intravenously. Many antifungals interact with TKIs through CYP3A4, so dose adjustments and careful drug-interaction checks are essential. Regular liver-function tests help detect toxicity.
17. Antiviral drugs (e.g., acyclovir)
Antivirals protect against reactivation of viruses such as herpes simplex or varicella-zoster in immunocompromised patients. Prophylactic low doses or full treatment doses can be used depending on risk and symptoms. They reduce painful outbreaks and serious complications in vulnerable people. Kidney function must be monitored with some antiviral agents.
18. Granulocyte colony-stimulating factor (G-CSF, e.g., filgrastim)
G-CSF stimulates bone marrow to produce more neutrophils and can shorten the duration of severe neutropenia after intensive therapy. In CML it is used selectively, for example in post-transplant settings or chemotherapy for blast crisis. It is usually given as a small daily injection for a few days. Side effects include bone pain and, rarely, spleen enlargement or rupture, so monitoring is needed.
19. Erythropoiesis-stimulating agents (ESAs)
ESAs such as erythropoietin are sometimes used to treat symptomatic anaemia in cancer patients when transfusions are not enough or not appropriate. They stimulate red blood cell production in the bone marrow. Because ESAs can increase clotting risk and might affect some cancer outcomes, they are used cautiously, following strict guidelines. In CML, their use is individualised.
20. Anti-emetics and supportive symptom drugs (e.g., ondansetron, loperamide)
TKIs and chemotherapy can cause nausea, vomiting or diarrhoea. Anti-emetic drugs like ondansetron help control nausea, and loperamide can reduce diarrhoea when infection is excluded. These medicines do not treat CML itself but make it easier to continue important cancer treatment. Hydration and electrolyte monitoring remain important alongside symptom drugs.
Dietary molecular supplements
Important: None of these supplements cure CML or replace TKIs. Always check for drug interactions, especially with TKIs metabolised by CYP3A4.
1. Vitamin D
Vitamin D supports bone health and immune function. Many people with cancer have low levels, so doctors sometimes prescribe supplements based on blood tests. Usual doses range from daily low doses to short courses of higher doses if deficiency is severe. Adequate vitamin D may help maintain bone strength in patients on long-term TKIs or steroids.
2. Omega-3 fatty acids (fish oil)
Omega-3 fats may have anti-inflammatory and heart-protective effects. They are sometimes used to support cardiovascular health, which is important for patients taking TKIs with vascular risks. Typical supplemental doses are in the 1–2 g/day range in many studies, but exact dosing should be individualised to avoid bleeding risks. People on blood thinners need medical advice before using high doses.
3. Probiotics
Probiotic bacteria in capsules or fermented foods may help maintain gut flora disturbed by antibiotics and TKIs. They can support digestion, reduce some types of diarrhoea and improve general gut comfort. However, in very immunocompromised patients, living bacteria supplements may pose a small risk, so haematology guidance is essential.
4. Curcumin (turmeric extract)
Curcumin is studied for anti-inflammatory and potential anti-cancer effects in laboratory models. In clinical practice it is sometimes used as a general wellness supplement, but it can affect drug-metabolising enzymes and platelets. Doses and product quality vary widely, and evidence in CML is limited. For safety it should only be taken after checking interactions with the treating team.
5. Green tea catechins (EGCG)
Green tea extracts contain catechins such as EGCG, which show antioxidant and anti-proliferative effects in lab studies. However, concentrated extracts can sometimes affect liver enzymes and drug levels. If used, doses should be modest and part of a monitored plan, not a replacement for standard therapy. Drinking normal amounts of tea is usually safer than high-dose capsules.
6. Selenium
Selenium is a trace mineral involved in antioxidant enzymes and immune function. In moderate amounts it may help support general health, but high doses are toxic. If blood tests show deficiency or diet is very poor, carefully dosed supplements can be considered. Over-supplementation can cause hair loss, nail changes and nerve problems.
7. B-complex vitamins (including folate and B12)
B vitamins are essential for red blood cell production and nerve function. Deficiency can worsen fatigue and anaemia symptoms. Supplementation is usually given only when deficiency is documented or diet is clearly poor, because very high doses can interact with some medicines or mask other problems. A standard multivitamin is usually enough for most patients.
8. Coenzyme Q10
Coenzyme Q10 is sometimes used to support heart and muscle energy metabolism. Evidence in CML is limited, but some people take low–moderate doses to help with fatigue or statin-related muscle symptoms. Since TKIs can have cardiovascular effects, any heart-focused supplement should be discussed with a cardiologist or haematologist.
9. L-glutamine
Glutamine is an amino acid important for gut and immune cell function. In some settings it is used to help manage mucositis or gut side effects from chemotherapy, though data are mixed. In CML, if used, it should be part of a supervised nutrition plan rather than self-prescribed. Kidney and liver function should be considered.
10. Melatonin
Melatonin is a hormone that helps regulate sleep; it also has some experimental anti-cancer and antioxidant actions. In CML, it may be considered at night in low doses to improve insomnia linked to anxiety or steroid use. Because it can interact with other sedatives and has hormonal effects, it should be used under medical advice.
Immunity-boosting, regenerative and stem-cell-related drugs
1. Granulocyte colony-stimulating factor (G-CSF, filgrastim / pegfilgrastim)
G-CSF is given as injections to stimulate the bone marrow to make more neutrophils after intensive chemotherapy or transplant. It reduces the length of severe neutropenia and lowers infection risk, helping the immune system recover faster. Typical schedules are short courses after chemo cycles, with dose based on weight and blood counts. Side effects include bone pain and rarely spleen problems, so monitoring is essential.
2. Erythropoiesis-stimulating agents (ESAs)
ESAs stimulate red blood cell production and can help people with symptomatic anaemia reduce transfusion needs. They mimic natural erythropoietin and are given as injections at intervals. Because of possible risks such as clotting and effects on cancer progression in some settings, their use is careful and guideline-based. In CML they are mainly supportive in complex cases.
3. Thrombopoietin receptor agonists (e.g., eltrombopag – selected cases)
These drugs stimulate platelet production via thrombopoietin receptors and are sometimes used in immune-mediated thrombocytopenia or post-treatment low platelets. Their role in CML is limited and highly specialised, often around transplant or complex immune complications. They require close monitoring for liver effects and thrombotic events.
4. Intravenous immunoglobulin (IVIG)
IVIG contains pooled antibodies from donors and is used in some immune-mediated complications, such as severe immune thrombocytopenia or recurrent infections due to antibody deficiency. It temporarily boosts immune function and modulates immune responses. Side effects can include headache, infusion reactions, kidney strain and, rarely, thrombosis, so it is given in hospital with monitoring.
5. Mesenchymal stem-cell–based therapies (experimental)
Mesenchymal stem cells are being studied for their ability to repair tissue and modulate immunity, especially after transplant-related complications. In CML they are not standard treatment but may be part of clinical trials in transplant centres. Their use is tightly regulated because long-term safety and benefit data are still evolving. Patients should only receive such therapies in recognised research settings.
6. Allogeneic haematopoietic stem cell transplantation (drug-assisted)
Although listed as surgery/procedure, transplant relies on powerful chemotherapy and sometimes radiation plus stem-cell infusion. It replaces the diseased marrow with donor stem cells that can grow a new, healthy immune and blood-forming system. Transplant is usually reserved for advanced-phase or TKI-resistant CML because of high risks such as graft-versus-host disease and infections. Many supportive drugs, growth factors and immunosuppressants are used around transplant to help engraftment and control complications.
Surgeries and invasive procedures
1. Allogeneic haematopoietic stem cell transplantation
This is the main “curative-intended” procedure for CML and involves giving high-dose chemotherapy (sometimes with radiation) followed by infusion of donor stem cells. It requires central venous access, hospital stay in a specialised unit, and long-term follow-up. Transplant is considered when TKIs fail or in aggressive phases, weighing relapse risk against procedure risk.
2. Central venous catheter (port or Hickman line) placement
Long-term intravenous access devices are implanted under the skin or into a large vein to allow repeated blood tests, chemotherapy and transfusions. The procedure is usually done under local or light general anaesthesia. It reduces the need for repeated needle sticks but can be complicated by infection or thrombosis, so good line care is vital.
3. Splenectomy (removal of the spleen)
Before modern TKIs, an enlarged spleen causing pain or blood-cell destruction sometimes required removal. Today it is rare, but may still be considered in selected cases with massive splenomegaly not responding to drug therapy. The operation requires general anaesthesia and carries risks of bleeding and infection, so patients receive special vaccines before or after surgery.
4. Leukapheresis
Leukapheresis is a machine-based procedure that removes excess white cells from the blood when counts are extremely high and causing symptoms such as vision changes or breathing difficulty. Blood is taken from one line, white cells are filtered out, and the rest is returned. It is a short-term emergency measure used alongside drugs like hydroxyurea and TKIs.
5. Surgical management of treatment complications
Occasionally, complications such as severe infections, bowel perforation, or bone damage may need surgical treatment. These are not specific to CML but to its treatments and associated risks. Decisions are made by multidisciplinary teams including haematologists, surgeons and intensivists, aiming to stabilise the patient while continuing cancer control.
Prevention and risk-reduction tips
Avoid tobacco: Never start smoking, and seek help to stop if you already smoke to lower cardiovascular and secondary cancer risks.
Limit alcohol: Keep alcohol intake low or avoid it, especially if liver tests are abnormal or you take hepatotoxic drugs.
Maintain healthy weight and regular activity: Aim for a healthy BMI and regular physical activity to support heart health and general resilience.
Avoid unnecessary radiation and harmful chemicals: Limit exposure to benzene, strong solvents, and avoid unneeded CT scans or x-rays where safe alternatives exist.
Stay up to date with recommended vaccines: Follow your haematology team’s vaccine plan for flu, COVID-19, and pneumococcal infections.
Adhere strictly to TKI therapy: Take TKIs exactly as prescribed and do not stop without specialist advice to prevent progression.
Avoid grapefruit, Seville oranges, starfruit and St John’s wort: These foods and herbs can dangerously change levels of many TKIs.
Review all medicines and supplements with your team: This includes OTC drugs and herbal products to prevent harmful interactions.
Protect skin and mouth: Daily gentle skin and oral care lowers risk of infections and treatment interruptions.
Attend all follow-up appointments and blood tests: Regular molecular monitoring of BCR-ABL1 levels helps detect resistance early and improve long-term outcomes.
When to see doctors or seek urgent care
People with BCR-ABL positive CML should contact their haematology team urgently or go to emergency care if they have fever above local thresholds (often around 38°C), chills, or feel suddenly very unwell, because neutropenic sepsis can be life-threatening. New or rapid-onset shortness of breath, chest pain, severe headache, weakness on one side of the body, or sudden vision changes may signal blood clots or bleeding and need immediate assessment, especially in patients on TKIs with vascular risks. Unusual bruising, nosebleeds that do not stop, blood in urine or stools, or very heavy menstrual bleeding suggest low platelets or clotting problems. Persistent severe abdominal pain, very swollen spleen feeling, confusion, or reduced urine could indicate tumour lysis, splenic issues or serious infection. Any unexpected and severe side effect after starting or changing TKIs should be reported quickly so doses can be adjusted safely.
What to eat and what to avoid
Eat a rainbow of fruits and vegetables to supply vitamins, minerals and antioxidants that support general health and recovery.
Choose lean proteins such as fish, poultry, eggs, beans and lentils to help repair tissues and maintain muscle mass during treatment.
Include whole grains like brown rice, oats and whole-wheat bread for energy and fibre to support bowel function.
Stay well hydrated with water, herbal teas and clear soups, especially if you have diarrhoea, fever or are on drugs that affect kidneys.
Avoid grapefruit, Seville oranges, starfruit and their juices, because they inhibit CYP3A4 and can dangerously increase TKI levels.
Avoid unpasteurised dairy, raw eggs, raw fish and undercooked meat, especially if your neutrophil count is low, to reduce infection risk.
Limit very processed meats, sugary drinks and deep-fried fast foods, which add calories but little nutrition and may worsen cardiovascular risks.
Be careful with herbal supplements such as St John’s wort, kava or strong citrus extracts, which can strongly alter TKI metabolism.
Use small, frequent meals and nutrient-dense snacks (nuts, yogurt, shakes) if you have nausea or poor appetite.
Ask for a dietitian referral if you lose weight, have diabetes, kidney disease, or persistent gut problems, so your diet can be tailored to your needs.
Frequently asked questions
1. Is BCR-ABL positive CML curable?
For many people, CML is now a long-term, very controllable condition rather than a rapidly fatal cancer. TKIs can drive the disease into deep molecular remission, and in some carefully selected patients, treatment can even be safely stopped under strict monitoring. Allogeneic stem cell transplantation can be curative but has higher risks, so it is reserved for specific situations.
2. How long do I need to take TKIs?
Most patients need to take TKIs daily for many years. Some people with stable deep responses for a long time may enter carefully supervised “treatment-free remission” programmes. Stopping on your own is dangerous, because disease can return or progress silently; decisions must always be guided by a specialist.
3. What is BCR-ABL monitoring and why is it important?
Regular blood or marrow tests measure BCR-ABL1 transcripts using sensitive PCR methods. These results show how well the TKI is working and help doctors decide whether to continue, change dose or switch to another TKI. Hitting early milestones (like BCR-ABL1 ≤10% at 3 and 6 months) is linked with better long-term outcomes.
4. Can lifestyle changes replace drug treatment?
No. Healthy lifestyle choices like not smoking, eating well and exercising are very helpful, but they cannot replace TKIs, which directly block the cancer-driving BCR-ABL protein. Lifestyle changes are best seen as partners to drug treatment, improving strength, heart health and overall wellbeing.
5. Is it safe to become pregnant while on TKIs?
Most TKIs can harm an unborn baby and are not considered safe in pregnancy. People who may wish to have children should have detailed counselling about timing, temporary drug changes, and fertility preservation before intensive therapy. Each case is individual, and decisions must be made with both haematology and obstetric specialists.
6. What if I forget a dose of my TKI?
In general, if you realise fairly soon, you may be told to take the missed dose, but if it is almost time for the next one, you usually skip it and continue as normal. You should not double up to “catch up,” because this can raise side-effect risk. Exact advice differs between drugs and should follow the patient leaflet and your doctor’s instructions.
7. Why must I avoid grapefruit and similar fruits?
Grapefruit, Seville oranges, starfruit and some other fruits contain compounds that block CYP3A4, a key enzyme that breaks down many TKIs. If this enzyme is blocked, drug levels can rise several-fold, increasing risks like heart rhythm problems or liver damage. Because the effect is unpredictable, complete avoidance is recommended.
8. What side effects should I report immediately?
You should urgently report fever, chills, bleeding, chest pain, shortness of breath, severe headaches, sudden neurological symptoms, or swelling and pain in one leg. These may signal infection, low counts, clots or bleeding, especially with second- and third-generation TKIs. Early reporting allows quick treatment and may prevent serious outcomes.
9. Can CML come back after a good response?
Yes, relapse or loss of response can occur, especially if medicines are missed, drug levels are too low, or resistance mutations develop in BCR-ABL. Regular BCR-ABL testing and clinic visits help detect relapse early. If resistance appears, switching to another TKI or adding other therapies can often regain control.
10. Do TKIs increase my heart and blood vessel risk?
Some TKIs, particularly nilotinib and ponatinib, are linked with higher rates of arterial events such as heart attacks and strokes in some patients. Doctors therefore check blood pressure, cholesterol, diabetes and smoking status, and treat risk factors aggressively. Choosing the right TKI involves balancing cancer control with each person’s cardiovascular profile.
11. Is transplant still needed now that TKIs exist?
Transplant is now used much less often than before TKIs, but it remains important for advanced-phase disease, T315I mutation not controlled by TKIs, or multiple TKI failure. It offers a chance of cure but carries high short- and long-term risk, so it is reserved for selected higher-risk patients. Many people with chronic-phase CML never need a transplant.
12. Can children and teenagers get CML?
Yes, CML can occur at any age, though it is more common in adults. Treatment principles are similar, but doses, side-effect monitoring and long-term growth and fertility issues need special attention. Paediatric or adolescent–young-adult (AYA) haematology teams usually coordinate care for younger patients.
13. How often will I need blood tests and visits?
Early in treatment, blood tests and BCR-ABL monitoring are quite frequent (for example every 3 months or sooner) to check response and safety. As responses deepen and stabilise, intervals may lengthen, but regular monitoring continues for years. Your exact schedule follows guideline recommendations and your individual situation.
14. Can complementary therapies like yoga or acupuncture help?
Gentle complementary therapies such as yoga, relaxation, massage or acupuncture (when platelets are safe) can help with stress, sleep and pain. They should not replace TKIs or medical treatment and should always be discussed with your team, especially if they involve herbs or supplements. Safe mind–body therapies can improve quality of life when integrated with standard care.
15. Where can I get reliable information and support?
Trusted sources include national cancer societies, leukaemia foundations, and patient-guideline organisations such as NCCN. They provide up-to-date information on treatments, side effects, clinical trials and practical living tips. Support groups, both local and online, can offer emotional help and shared experiences alongside professional advice.
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.
