Chronic neutrophilic leukemia is a very rare blood cancer. It starts from the bone marrow, where blood cells are made. In this disease, the body makes too many mature neutrophils, which are a type of white blood cell that normally fight infections. These extra neutrophils build up in the blood and bone marrow and can also collect in organs like the spleen and liver. CNL is grouped with a family of diseases called myeloproliferative neoplasms, and it is BCR::ABL1-negative, which means it is different from classic chronic myeloid leukemia (CML).
CNL is “chronic,” so the extra neutrophils stay high for a long time. The white cell count is usually very high (often above 25,000 cells per microliter), and most of these cells are fully mature neutrophils, not blasts (very young cells). The bone marrow is usually very “crowded” (hypercellular) because the neutrophil cell line is growing too much. There is usually no Philadelphia chromosome and no BCR::ABL1 fusion gene.
Chronic neutrophilic leukemia is a very rare blood cancer in the group of BCR-ABL–negative myeloproliferative neoplasms. In CNL, the bone marrow makes too many mature neutrophils (a type of white blood cell). These cells spill into the blood and can build up in the spleen and liver. Many patients have a mutation in a gene called CSF3R, which drives the over-production of neutrophils and is now part of the diagnostic criteria.[]
People with CNL may feel well at first or may have tiredness, weight loss, night sweats, bone pain, infections, or a very enlarged spleen. Over time, CNL can cause serious problems like blood clots, infections, or transformation to acute myeloid leukemia (AML). Because the disease is rare, there is no single standard treatment, but experts use a mix of cytoreductive drugs (to lower counts), targeted drugs, and sometimes allogeneic stem cell transplant, which is the only known potentially curative option.[]
A very important feature of CNL is that in most patients there is a change (mutation) in a gene called CSF3R. This gene helps control the growth signal for neutrophils. The mutation turns this signal on too strongly, so neutrophils keep growing even when the body does not need them. Other genes, like ASXL1 and SETBP1, may also be changed and can make the disease more aggressive.
CNL is extremely rare. Studies show an incidence around 0.1 to 1 case per 1,000,000 people per year. Most patients are older adults, often in their 60s or 70s, although younger adults and even adolescents have been reported. Many patients are first found by chance when a routine blood test shows a very high neutrophil count.
Other names of chronic neutrophilic leukemia
Doctors and books may use different names for the same disease. Chronic neutrophilic leukemia is often shortened to “CNL.” In British English it may be written as “chronic neutrophilic leukaemia.” Some sources use “neutrophilic leukemia” or “leukemia neutrophilic chronic” as synonyms. All of these terms refer to the same rare myeloproliferative neoplasm with persistent neutrophilia and no BCR::ABL1 fusion.
Types of chronic neutrophilic leukemia
Doctors sometimes divide CNL into “types” based on genetic changes or the situation in which it appears. These groupings help research and treatment planning but all are still considered CNL.
CNL with CSF3R mutation – this is the most common and “classic” type, and CSF3R T618I is the best known mutation.
CNL without CSF3R mutation – much less common; diagnosis needs strong clinical and lab evidence and careful exclusion of other causes of neutrophilia.
CNL with additional mutations (for example ASXL1, SETBP1, SRSF2) – these added mutations may be linked with more aggressive disease or higher chance of progression.
CNL associated with other blood diseases (for example myelodysplastic syndromes or multiple myeloma) – very rare overlap situations where CNL appears together with another marrow disorder.
Even though these types look slightly different under the microscope or in genetic tests, they share the key features: long-lasting very high neutrophils, hypercellular bone marrow, and no BCR::ABL1 fusion.
Causes and risk factors
The exact cause of CNL is not fully known. Doctors think it is a clonal disease, which means it starts from one abnormal stem cell in the bone marrow that grows out of control. Below are 20 factors that are known or suspected to play a role. Some are proven causes (like gene mutations). Others are general risk factors seen in many blood cancers, but not proven only for CNL.
CSF3R mutation (main cause)
The most important known cause is an acquired mutation in the CSF3R gene. This mutation gives a constant “grow” signal to neutrophil precursors, so they keep multiplying even when the body does not need them. Most patients with CNL have this mutation.Other gene mutations (ASXL1)
Many patients also have mutations in the ASXL1 gene. This gene helps control how DNA is packaged and read. When ASXL1 is mutated, the bone marrow cells may become more unstable and the disease may behave more aggressively.SETBP1 mutation
SETBP1 mutations are also seen in CNL and can increase cell survival and growth. When present together with CSF3R mutations, SETBP1 may be linked to worse outcomes and a higher chance of progression to acute leukemia.Other myeloid gene mutations (for example SRSF2, TET2, JAK2)
Some patients have additional changes in genes that control RNA splicing, epigenetics, or cell signaling. These changes can add to the abnormal growth signal and make the marrow cells more likely to form a neoplasm like CNL.Clonal stem cell origin
CNL comes from one hematopoietic stem cell in the bone marrow that becomes abnormal and copies itself many times. This “clone” takes over the normal marrow space and makes too many neutrophils. This clonal origin is a core feature of the disease.Older age
Most people with CNL are older adults, often over 60–70 years. As we age, our stem cells collect random DNA errors, and one of these errors can hit a gene like CSF3R and start a clonal disease. Age is therefore a strong risk factor.Slight male predominance
Some studies show a slightly higher number of men with CNL than women. The reason is not clear, but hormones, lifestyle, or environmental exposures might play a role. This is a weak but observed risk pattern.General genetic susceptibility
Even when no family pattern is obvious, some people may have background genetic differences that make their bone marrow more likely to develop clonal mutations. So far no single inherited gene has been clearly proven for CNL, but inherited susceptibility is suspected in some myeloid cancers.Previous myeloid disease (for example MDS or other MPN)
In rare cases, CNL appears in people who already have a myelodysplastic or myeloproliferative disease. Their bone marrow is already unstable, and new mutations, including CSF3R, can give rise to a CNL-type clone.Association with multiple myeloma
Some case reports describe CNL in people with multiple myeloma. The exact link is unclear. In some cases the neutrophilia may be a reaction to the myeloma, and in others there may be two separate clones. This overlap suggests that a disturbed marrow environment may encourage CNL-like changes.Chronic inflammation or infection (possible, not proven)
Long-lasting inflammation or infection can cause repeated activation of neutrophils and their growth signals. Over time, this constant stimulation could increase the chance that a stem cell gains mutations like CSF3R, though this is not firmly proven for CNL.Exposure to radiation (possible general risk)
High-dose radiation can damage DNA in bone marrow cells. For many leukemias, past radiation exposure is a known risk factor. For CNL specifically, direct proof is limited, but radiation is considered a possible general trigger of myeloid neoplasms.Exposure to certain chemicals (for example benzene)
Organic solvents such as benzene are well known to increase the risk of some blood cancers. While specific studies in CNL are lacking, similar myeloid neoplasms are linked to such exposures, so this is treated as a possible contributory factor.Previous chemotherapy for another cancer (possible secondary risk)
Some chemotherapy drugs can damage DNA in stem cells and lead to therapy-related myeloid neoplasms. CNL after chemotherapy is rarely reported, but the principle from other myeloid cancers suggests this could sometimes contribute.Bone marrow microenvironment changes
The “soil” of the marrow (support cells, blood vessels, and chemical signals) may change with age, disease, or treatment. These changes can favor the growth of an abnormal clone with CSF3R mutations over normal stem cells.Immune system changes in older adults
With age, the immune system sometimes becomes less able to remove abnormal cells. This “immune escape” may allow mutated clones to survive and grow, leading to diseases like CNL.Oxidative stress in the marrow
Oxidative stress means damage from reactive oxygen species inside cells. Chronic oxidative stress can injure DNA and favor mutations in genes that control growth, including myeloid genes. This mechanism is suggested in many blood cancers and may also contribute to CNL.Epigenetic changes
Epigenetic changes do not change the DNA code but change how genes are turned on or off. Mutations in genes like ASXL1 affect epigenetic marks and can push stem cells towards uncontrolled growth, supporting the CNL clone.Random (sporadic) mutation events
In many patients, there is no known exposure or family history. The disease may simply result from random DNA damage in one stem cell, followed by survival and expansion of that cell. This “chance” factor is common in rare cancers.Progression from early clonal neutrophilia to full CNL
Some people may have a smaller neutrophil clone for a time, with mild neutrophilia. Over years, extra mutations or changes might allow this clone to grow stronger and fulfill full CNL criteria. This stepwise clonal evolution has been suggested in research on myeloid neoplasms.
Symptoms and signs
Not everyone with CNL has symptoms at diagnosis. Some people feel normal, and the problem is found only on a blood test. When symptoms appear, they often come from very high white cell counts, organ enlargement, or complications such as gout.
Tiredness and low energy (fatigue)
Many people with CNL feel very tired, weak, or “worn out” even after resting. This may be due to anemia (low red blood cells), chronic inflammation, or the general burden of the disease on the body.Fever or feeling hot
Some patients have fevers or episodes of feeling unusually warm. This may come from infections, because the immune system is not working normally, or from the disease itself, which can produce inflammatory substances.Night sweats
Heavy sweating at night, often soaking clothes or sheets, can be a sign of active blood cancer. It is a general “B symptom” seen in many myeloproliferative neoplasms, including CNL.Weight loss without trying
Some people lose weight even though they are not dieting. This can happen because the disease increases metabolism and reduces appetite, and because chronic inflammation uses a lot of energy.Full feeling in the left upper belly (splenomegaly)
The spleen, which sits under the left ribs, often becomes enlarged because it traps extra neutrophils and may be directly infiltrated. Patients may feel fullness, discomfort, or pain in this area, especially after eating.Pain or discomfort in the upper right belly (hepatomegaly)
The liver can also become enlarged and firm because of neutrophil infiltration. This may cause a dull ache or a feeling of heaviness on the right side under the ribs.Easy bruising or bleeding
As the disease progresses, platelets (the cells that help blood clot) can become low or not work well. Patients may bruise easily, have nosebleeds, or notice bleeding from gums.Gout or joint pain
High turnover of blood cells produces extra uric acid. This can form sharp crystals in joints, especially in the big toe, causing sudden painful swelling called gout. CNL patients may have gout attacks or chronic joint pain.Bone pain
Some patients feel deep, aching pain in bones, especially in the legs or back. This may come from the crowded bone marrow where neutrophil precursors are expanding.Frequent infections
Even though there are many neutrophils, they may not work normally. Patients can have repeated infections such as pneumonia, skin infections, or urinary infections. In severe cases, serious infections like sepsis can occur.Headaches or dizziness
Very high white cell counts can make blood thicker and flow less easily. This can cause headaches, dizziness, or a feeling of pressure in the head. Anemia can also contribute to these symptoms.Shortness of breath
Anemia or high cell counts can reduce oxygen delivery and make the heart and lungs work harder. Patients may feel breathless when walking or climbing stairs, even if they were fit before.Pale skin
If red blood cells become low, skin and the inside of the eyelids can look pale. This is a sign of anemia, which often appears as CNL advances.Enlarged lymph nodes (less common)
CNL mainly affects blood, marrow, spleen, and liver. Lymph node enlargement is less common but can occur in some patients and may reflect disease spread or another overlapping condition.No symptoms (found by chance)
Many people with CNL have no symptoms at first. The diagnosis is sometimes made when a routine blood test, done for another reason, shows a very high neutrophil count.
Diagnostic tests for chronic neutrophilic leukemia
Doctors use many tests together to diagnose CNL. They do not rely on only one test. First they confirm that neutrophils are very high and persistent. Then they rule out other causes such as infections, other myeloproliferative neoplasms, and reactive neutrophilia. Finally they look for CSF3R and other mutations.
Physical exam tests
General physical examination
The doctor looks at the whole body. They check the skin, eyes, mouth, breathing, heart sounds, and general condition. They look for signs like pale skin, bruises, or weight loss, which can suggest a chronic blood disease such as CNL.Vital signs check (temperature, pulse, blood pressure, breathing rate)
Basic measurements show how the body is coping. Fever can suggest infection or disease activity. Fast pulse or low blood pressure can show anemia, infection, or strain on the heart from the high cell counts.Abdominal exam for spleen and liver
The doctor feels (palpates) and taps (percusses) the abdomen to check if the spleen or liver is enlarged. A big spleen or liver is very common in CNL and supports the diagnosis when seen together with a high neutrophil count.Lymph node examination
The doctor gently feels the neck, armpits, and groin areas for enlarged lymph nodes. In CNL, lymph nodes are usually normal or only mildly enlarged, which helps to distinguish it from some lymphoid leukemias and lymphomas.
Manual tests (bedside hands-on checks)
Manual spleen palpation (detailed)
The doctor uses their hands to feel carefully along the left upper abdomen while the patient breathes in and out. They judge exactly how far the spleen tip extends below the ribs. This manual test helps track spleen size over time and see if treatment is working.Manual liver palpation
The doctor feels under the right ribs to detect liver enlargement and any tenderness. In CNL, a firm, smooth enlarged liver can occur because of neutrophil buildup. This finding supports the picture of a myeloproliferative neoplasm.Manual bone tenderness check
The doctor presses gently along the bones of the legs, arms, or spine to look for tenderness that may suggest very active bone marrow. Pain in these areas, together with lab results, can suggest a marrow disease such as CNL.Manual joint examination for gout
The doctor bends and moves the joints, especially the big toes and ankles, and looks for redness, warmth, and swelling. If gout attacks are present, this supports a picture of high cell turnover, which is often seen in CNL and other myeloproliferative neoplasms.
Lab and pathological tests
Complete blood count (CBC) with differential
This key blood test measures the number of red cells, white cells, and platelets. In CNL, the white cell count is very high, and most white cells are neutrophils. The differential shows how many of each type of white cell are present and confirms that neutrophils make up most of the increase.Peripheral blood smear
A smear is a thin layer of blood looked at under the microscope. In CNL, it shows many mature segmented neutrophils and band forms, with few very immature cells. There is usually no significant dysplasia (abnormal shape) in these cells, which helps separate CNL from other diseases.Leukocyte alkaline phosphatase (LAP) score
LAP is an enzyme in neutrophils. In older diagnostic criteria, CNL often showed a high LAP score, while some other leukemias did not. Today LAP is less central but still can support the idea that the neutrophils are reactive and active.Serum uric acid and LDH (lactate dehydrogenase)
These blood tests measure products of cell breakdown. In CNL, both uric acid and LDH are often high because many cells are being produced and destroyed. High uric acid also explains why gout is common in these patients.Serum vitamin B12 level
Vitamin B12 can be very high in CNL and some other myeloproliferative diseases. This happens because white cells release proteins that carry B12. A very high B12 level, together with neutrophilia, supports a myeloproliferative process rather than a simple infection.Bone marrow aspiration and biopsy
A small amount of liquid bone marrow and a tiny core of bone are taken, usually from the hip bone. Under the microscope, CNL marrow is very crowded with neutrophil precursors and mature neutrophils, but blasts remain low. There is no marked dysplasia, and other cell lines may be relatively reduced.Cytogenetic testing (karyotype and FISH, including BCR::ABL1)
These tests study the chromosomes of marrow cells. In CNL, there is usually no Philadelphia chromosome and no BCR::ABL1 fusion, which helps rule out chronic myeloid leukemia. Other chromosomal changes are rare but may be seen in some cases.Molecular testing for CSF3R and other mutations
DNA from blood or bone marrow is checked for specific gene mutations. Finding an activating CSF3R mutation, especially CSF3R T618I, is now a key part of the diagnosis. Testing may also look for ASXL1, SETBP1, and other gene changes that give extra prognostic information.
Electrodiagnostic tests
Electrocardiogram (ECG)
An ECG records the heart’s electrical activity. It does not diagnose CNL directly, but it helps see how the heart is coping with anemia, high blood thickness, or any treatment side effects. It is important to check the heart when planning medicines that might affect heart rhythm.Nerve conduction study (if there is nerve-related symptom)
In some patients with tingling or numbness, nerve conduction tests may be done. They measure how quickly signals travel along nerves. These tests do not diagnose CNL but help see if symptoms are from nerve damage, which could be related to high uric acid, treatment, or other overlapping conditions.
Imaging tests
Abdominal ultrasound
Ultrasound uses sound waves to create pictures of internal organs. It is painless and can clearly show the size of the liver and spleen. In CNL, ultrasound often confirms splenomegaly and hepatomegaly and helps follow these over time.CT scan of chest and abdomen (sometimes PET-CT)
CT scans give detailed cross-section images of the body. They show organ size, lymph nodes, and any unusual masses. In CNL, CT can confirm organ enlargement, look for complications like infections, and help exclude other causes of neutrophilia such as hidden cancers or deep abscesses. PET-CT may be used in complex cases to see metabolic activity.
Non-Pharmacological Treatments (Therapies and Others)
Below are supportive and lifestyle treatments that work together with medicines, not instead of them. Always discuss them with your hematologist.
Regular hematology follow-up and monitoring
Close follow-up with a blood cancer specialist is one of the most important “non-drug” treatments. Frequent blood counts, spleen checks, and mutation tests help your team see if CNL is stable, progressing, or transforming. Early action allows dose changes, switch of therapy, or referral for transplant before serious complications appear.[]Infection-prevention measures
Even when neutrophils are high, their function may be abnormal, and some treatments lower immunity. Good hand-washing, dental care, safe food handling, staying away from sick contacts, and up-to-date vaccines (influenza, COVID-19, pneumococcus, etc.) reduce infection risk and hospital admissions and are recommended in most leukemia care pathways.[]Vaccination under specialist guidance
Inactivated vaccines are usually encouraged, especially before major treatments like transplant. Live vaccines may be restricted. A vaccination plan helps prevent pneumonia, flu, and other serious infections in CNL, particularly in patients on JAK inhibitors or post-transplant.[]Nutrition counselling and weight management
Many patients lose weight or appetite because of splenomegaly, fatigue, or treatment side effects. A dietitian can design a high-protein, energy-dense diet with safe foods, limit alcohol, and address nausea or taste changes. Good nutrition supports immunity, wound healing, and tolerance of chemotherapy or transplant.[]Moderate physical activity and physiotherapy
Gentle exercise (walking, stretching, light resistance work) helps maintain muscle mass, improves fatigue, mood, and sleep. Supervised physiotherapy is valuable if there is de-conditioning, bone pain, or post-transplant weakness. Activity levels are adapted to anemia, platelet counts, and general fitness.[]Fatigue management and energy-saving strategies
Simple strategies like pacing, planned rest breaks, prioritizing tasks, and using assistive devices help people cope with severe tiredness, which is common in CNL and myeloproliferative neoplasms. Occupational therapists can teach practical methods to continue daily life safely.[]Psychological support and counselling
Living with a rare leukemia brings anxiety, fear of relapse, and social stress. Access to psycho-oncology services, support groups, and counselling improves quality of life, treatment adherence, and coping, especially around transplant and long hospital stays.[]Social work and financial counselling
CNL care may require travel, time off work, and expensive medicines. Hospital social workers can assist with insurance, disability benefits, reimbursement programs, transport, and accommodation near transplant centers, reducing non-medical barriers to treatment.[]Smoking cessation and alcohol moderation
Smoking and heavy alcohol use increase infection risk, liver problems, and cardiovascular disease, all of which can worsen outcomes in myeloproliferative neoplasms. Stopping smoking and moderating alcohol supports overall health and reduces problem-bleeding or clotting.[]Splenic symptom management (non-surgical)
Before considering surgery or radiation, non-drug measures such as small frequent meals, avoiding heavy lifting, and protecting the abdomen help reduce pain and risk of splenic injury when the spleen is enlarged. These strategies are often combined with cytoreductive therapy that shrinks the spleen.[]Careful use of NSAIDs and antiplatelet drugs
Many CNL patients have low platelets or are at bleeding risk. Non-pharmacological pain approaches (heat, cold packs, physiotherapy, relaxation) may allow reduced use of NSAIDs or aspirin, lowering bleeding risk. Pain plans are tailored with the hematology team.[]Oral and dental care programs
Regular dental checks, soft toothbrushes, fluoride toothpaste, and prompt treatment of mouth infections lower the chance that oral bacteria become bloodstream infections, especially during neutropenia or after transplant.[]Safe pregnancy and fertility planning
Some drugs used in CNL are teratogenic or affect fertility. Early reproductive counselling, fertility preservation before chemotherapy or transplant, and careful planning of pregnancy with hematology and obstetrics teams are important non-drug interventions.[]Sun protection and skin surveillance
Hydroxyurea and some other therapies increase skin-cancer risk. Using sunscreen, protective clothing, and regular skin checks helps reduce the risk of cutaneous malignancies in long-term survivors.[]Bone health support
Long-term steroids (for graft-versus-host disease) and inactivity can weaken bones. Bone-strengthening lifestyle measures include weight-bearing exercise within limits, calcium-rich foods, vitamin D adequacy, and fall-prevention strategies.[]Sleep hygiene techniques
Pain, night sweats, and anxiety may disturb sleep. Simple methods like regular sleep times, limiting screens before bed, relaxation breathing, and a cool dark bedroom can improve rest, which in turn supports immunity and mood.[]Palliative care and symptom-control clinics
Palliative care is not only for end of life. Symptom-control teams help with pain, breathlessness, nausea, psychological distress, and advance-care planning throughout the disease course, improving quality of life even when active treatment continues.[]Patient education about “red flag” symptoms
Teaching patients and families to recognize fever, sudden left-sided abdominal pain, bleeding, or new neurologic symptoms leads to faster emergency care and better outcomes. Education is a powerful non-drug treatment.[]Telemedicine and remote monitoring
For patients who live far from specialized centers, telehealth appointments, remote symptom reporting, and local lab testing help keep CNL under control while limiting travel and exposure to infections.[]Multidisciplinary team conferences
Regular meetings between hematologists, transplant physicians, radiologists, pathologists, and nurses help review complex CNL cases, integrate new evidence (for example, about CSF3R-targeted strategies or JAK inhibitors), and choose the safest individualized plan.[]
Drug Treatments
Very important: Doses and schedules below are general examples from FDA labels or published studies in other diseases, not specific prescriptions for you. CNL is rare, and many drugs are used off-label. Always follow the exact plan from your hematologist.
Hydroxyurea – oral cytoreductive agent
Hydroxyurea is the most commonly used first-line drug to lower very high neutrophil counts and relieve spleen-related symptoms in CNL. It is an antimetabolite that blocks DNA synthesis in rapidly dividing cells.[] FDA-approved products (HYDREA, DROXIA, SIKLOS, XROMI) use starting doses around 15 mg/kg/day in sickle-cell disease, adjusted by counts, with bone-marrow suppression, GI upset, and skin cancer risk as key side effects.[]Ruxolitinib (Jakafi) – JAK1/2 inhibitor
Ruxolitinib blocks JAK-STAT signaling and is FDA-approved for myelofibrosis, polycythemia vera, and some graft-versus-host disease cases.[] In CNL, small studies and case reports show that 10–20 mg orally twice daily (dose adjusted to platelets) can reduce leukocytosis and spleen size, especially in CSF3R-mutated disease, but with risks of anemia, thrombocytopenia, infections, and herpes zoster.[]Pegylated interferon-alpha
Peg-IFN-α is an injectable immune-modulating drug used in some myeloproliferative neoplasms. Case reports show that pegylated interferon combined with ruxolitinib controlled neutrophil counts in CNL with germline CSF3R mutation.[] Dosing is individualized (for example, weekly injections), and side effects include flu-like symptoms, mood changes, thyroid dysfunction, and cytopenias.Cytarabine (Ara-C)
Cytarabine is a cytotoxic chemotherapy that interferes with DNA synthesis in dividing cells. It is mainly used when CNL accelerates or transforms to acute myeloid leukemia or in transplant conditioning. Side effects include severe bone-marrow suppression, mucositis, hair loss, and infection risk.[]Azacitidine
Azacitidine is a hypomethylating agent approved for myelodysplastic syndromes and some AML cases. In CNL with overlapping MDS/MPN features or high-risk mutations, azacitidine may be used to control disease or as a bridge to transplant. It is given by injection in cycles and can cause cytopenias, GI upset, and injection-site reactions.[]Decitabine
Decitabine is another hypomethylating drug used for higher-risk myeloid neoplasms. In selected CNL cases with disease evolution, it may help reduce blast percentage or stabilize counts before more intensive therapy. Main toxicities are neutropenia, thrombocytopenia, and infection.[]Busulfan
Busulfan is an alkylating agent mostly used now in conditioning regimens before allogeneic stem cell transplant. It damages DNA in bone-marrow cells so that donor cells can engraft. Side effects include prolonged cytopenias, lung toxicity, seizures (so anti-seizure prophylaxis is often used), and long-term malignancy risk.[]Fludarabine
Fludarabine is a purine analog chemotherapy, often combined with busulfan as reduced-intensity transplant conditioning. It suppresses the patient’s immune system and marrow to allow donor graft acceptance. Toxicities include profound immunosuppression, infections, and neurologic effects at high doses.[]Cyclophosphamide
Cyclophosphamide is used in some transplant protocols and occasionally for auto-immune complications. It cross-links DNA and is activated in the liver. Side effects include nausea, hair loss, bone-marrow suppression, infertility, and bladder toxicity (hemorrhagic cystitis).[]Antithymocyte globulin (ATG)
ATG is an immune-suppressive antibody preparation used in some transplant protocols and graft-versus-host prophylaxis. It reduces host T-cells to lower graft rejection. Infusion reactions, serum sickness, and infection risk are important side effects.[]Broad-spectrum antibiotics
When CNL patients develop neutropenic fever (for example, from treatment), early IV antibiotics are life-saving supportive drugs. They are not anti-leukemia medications but are essential to survive episodes of sepsis and severe infection.[]Antifungal and antiviral prophylaxis
Drugs such as azoles (antifungals) or acyclovir (antiviral) may be given during intensive chemotherapy or after transplant to prevent opportunistic infections. Doses are adjusted to kidney and liver function, and interactions with other drugs (including ruxolitinib) must be checked.[]Allopurinol
Allopurinol decreases uric acid production and is used to prevent or treat tumor lysis syndrome, which can occur when counts are rapidly lowered with chemotherapy or JAK inhibitors. Side effects include rash, liver test changes, and rarely severe hypersensitivity.[]Low-dose aspirin (in selected patients)
Low-dose aspirin may be used to reduce thrombotic risk in some myeloproliferative neoplasm patients, but in CNL it must be weighed carefully against bleeding risk, platelet count, and other drugs. It is not universal and should only be used under specialist advice.[]Granulocyte colony-stimulating factor (G-CSF)
In special situations after intensive chemotherapy or transplant, G-CSF may be used to speed neutrophil recovery. In classic untreated CNL it is usually not given, because it can worsen neutrophilia, but it has a role in post-treatment support.[]Intravenous immunoglobulin (IVIG)
IVIG can support immunity in patients with recurrent severe infections and low antibody levels, especially post-transplant. It is given by infusion and may cause headache, chills, or infusion reactions.[]Corticosteroids
Steroids such as prednisone or methylprednisolone are used mainly for graft-versus-host disease after transplant or for certain autoimmune complications. They help control inflammation but can cause weight gain, diabetes, bone loss, mood changes, and infection risk when used long term.[]Tyrosine kinase inhibitors (TKIs) in selected off-label cases
Some case reports have tried drugs such as dasatinib when specific signaling pathways are involved, but experience is limited and not standard. Benefit has been variable, and TKIs may cause cytopenias, fluid retention, and cardiac effects.[]Clinical-trial investigational agents (e.g., ruxolitinib phosphate)
Phase II trials have studied ruxolitinib formulations in CNL and atypical CML; enrollment in trials can give access to new targeted agents and careful monitoring.[]Supportive transfusion therapy (RBCs and platelets)
Red cell and platelet transfusions are drugs in the broader sense and are often needed when CNL or its treatment causes severe anemia or thrombocytopenia. They improve symptoms and prevent bleeding but can cause reactions and iron overload with repeated use.[]
Dietary Molecular Supplements (Supportive, Not Curative)
These supplements do not treat CNL directly but may support general health. Always check with your doctor for interactions with chemotherapy or JAK inhibitors.
Vitamin D – helps bone health, muscle function, and immune regulation; deficiency is common in cancer patients.
Omega-3 fatty acids (fish oil) – may support cardiovascular health and anti-inflammatory pathways, but high doses can affect bleeding.
High-protein oral nutrition supplements (whey/soy blends) – help maintain weight and muscle during treatment.
Probiotics (selected strains) – may help gut microbiome balance but must be used cautiously in immunocompromised patients.
Vitamin B12 – supports red-blood-cell production and nerve health when deficient.
Folate (folic acid) – important for DNA synthesis; supplementation is guided by lab levels and chemotherapy plan.
Iron (only if deficient) – replaces iron stores in true iron-deficiency anemia but must be avoided in iron overload.
Zinc – supports wound healing and immunity; overdose can disturb copper levels.
Selenium – trace mineral with antioxidant roles; excessive intake can be toxic.
Oral glutamine – sometimes used to support gut mucosa during chemotherapy, though evidence is mixed.
(Your team should individualize doses based on blood tests, kidney and liver function, and overall plan.)
Immunity-Boosting / Regenerative / Stem-Cell-Related Drugs
Again, these are specialist-only therapies used in defined settings.
Granulocyte colony-stimulating factor (G-CSF) – promotes neutrophil recovery after intensive therapy or transplant.
Thrombopoietin receptor agonists (e.g., eltrombopag) – can raise platelets in some marrow-failure settings; rarely used in classic CNL but may be considered post-transplant or in overlapping conditions.
Intravenous immunoglobulin (IVIG) – provides pooled antibodies to help prevent or treat serious infections in immunodeficient patients.
Mesenchymal stromal cell infusions – used experimentally or in severe steroid-refractory graft-versus-host disease to support tissue repair.
Donor lymphocyte infusions (post-transplant) – give extra donor T-cells to boost graft-versus-leukemia effect when relapse is suspected.
Allogeneic hematopoietic stem cell graft itself – the ultimate “regenerative” treatment, replacing the diseased marrow with healthy donor cells and offering a chance of cure.[]
Surgeries and Procedures
Allogeneic hematopoietic stem cell transplantation (allo-HSCT)
This complex procedure replaces the patient’s bone marrow with donor stem cells after high-dose conditioning chemotherapy (and sometimes radiation). It is currently the only treatment with curative potential in CNL but carries significant risks of infection, graft-versus-host disease, organ damage, and treatment-related death, so it is reserved for carefully selected patients.[]Splenectomy (surgical removal of spleen)
Rarely, when the spleen is massively enlarged, painful, destroying blood cells, and not controlled by drugs, removal may be considered. It can relieve pain and improve counts but increases lifelong infection risk, so vaccines and prophylactic antibiotics are important afterward.[]Splenic irradiation
Low-dose radiation to the spleen can temporarily shrink it and relieve pain in patients who are not surgical candidates. Effects are often short-lived, and cytopenias can worsen, so this is usually a palliative option.[]Central venous catheter insertion
Long-term lines or ports are placed surgically to allow repeated blood draws, chemotherapy, transfusions, and stem cell infusions. They improve treatment convenience but increase infection and clot risks, so strict line care is needed.[]Bone marrow biopsy and aspiration
This minor surgical procedure is essential for diagnosis, monitoring mutation status, and assessing transformation to AML. It guides key treatment decisions such as when to consider transplant or change systemic therapy.[]
Key Preventions and Lifestyle Safeguards
Keep all scheduled hematology and lab appointments.
Follow infection-prevention routines (hand hygiene, masks in crowded places during treatment, food safety).
Stay current with recommended vaccines after discussing timing with your team.
Avoid smoking and limit alcohol.
Tell your doctor before taking new over-the-counter medicines or supplements.
Protect your skin from the sun, especially if using hydroxyurea.
Maintain a balanced, nutrient-dense diet and adequate hydration.
Stay active within your limits to prevent clots and de-conditioning.
Keep an updated list of all medications and allergies with you.
Seek emergency care quickly for fever, heavy bleeding, sudden abdominal pain, or neurological symptoms.[]
When to See a Doctor Urgently
You should contact your doctor or emergency services immediately if you have:
Fever ≥ 38 °C (100.4 °F) or chills
Sudden or worsening shortness of breath or chest pain
New confusion, severe headache, or weakness on one side of the body
Heavy bleeding (vomiting blood, black stools, blood in urine, nosebleeds that do not stop)
Sudden, sharp pain or fullness under the left ribs (possible splenic crisis or rupture)
Any rapid change in symptoms that feels alarming or different from your usual pattern[]
For non-emergency issues (slow weight loss, mild fatigue, new aches), arrange an earlier clinic visit and blood tests.
Things to Eat and Things to Avoid
What to eat (general guidance):
Plenty of fruits and cooked vegetables for vitamins and fiber.
Lean proteins (fish, eggs, poultry, beans, lentils) to support muscle and immune function.
Whole grains (oats, brown rice) for steady energy.
Healthy fats from nuts, seeds, and olive or canola oil.
Calcium-rich foods (dairy or fortified plant milks) for bone health.
Adequate fluids (water, herbal teas, soups) to prevent dehydration.
Small, frequent meals if the spleen is large and appetite is low.
Foods high in iron only if you are iron-deficient and your doctor agrees.
Soft, easy-to-chew foods during mouth sores or after intensive therapy.
Culturally familiar foods prepared safely, to maintain enjoyment and intake.[]
What to avoid or limit:
Raw or undercooked meat, eggs, and seafood (infection risk).
Unpasteurized dairy products and juices.
Raw sprouts and poorly washed salads during high-risk treatment periods.
Excessive alcohol, which strains the liver and marrow.
Very salty processed foods that worsen blood pressure and fluid retention.
High-dose herbal products or supplements without medical review.
Grapefruit or Seville oranges if using drugs with known interactions (for example, ruxolitinib).
Smoking or vaping of any kind.
Energy drinks in large amounts, which may affect heart rhythm.
Crash diets or extreme fasting that cause weight loss and weakness.[]
Frequently Asked Questions (FAQs)
Is chronic neutrophilic leukemia curable?
The only treatment that currently offers a realistic chance of cure is allogeneic stem cell transplant. Many patients are not candidates because of age, other illnesses, or personal choice, but modern transplant outcomes in CNL are improving.[]How common is CNL?
CNL is extremely rare, making up a tiny fraction of all myeloproliferative neoplasms. Because it is so uncommon, much of our knowledge comes from small case series and registries rather than large randomized trials.[]What causes CNL?
Most cases are linked to acquired mutations in the CSF3R gene in bone-marrow stem cells. Other cooperating mutations in genes like SETBP1 or ASXL1 may influence prognosis. These mutations are not usually inherited, though rare germline cases exist.[]What is the role of hydroxyurea?
Hydroxyurea is often the first drug used to rapidly control very high neutrophil counts and spleen enlargement. It is convenient (oral) and relatively inexpensive but does not cure the disease and may lose effectiveness over time.[]What is the role of ruxolitinib?
Ruxolitinib is a JAK1/2 inhibitor approved for other myeloproliferative neoplasms. In CNL, small studies and reports show it can improve symptoms and blood counts, especially in CSF3R-mutated disease, but it remains an off-label, evolving option.[]Can CNL turn into acute leukemia?
Yes. A significant proportion of patients eventually progress to acute myeloid leukemia, especially those with high-risk mutations. Regular monitoring of blasts in blood and marrow helps detect this early.[]How is CNL different from chronic myeloid leukemia (CML)?
CML usually has the BCR-ABL1 (Philadelphia) chromosome and responds to tyrosine kinase inhibitors like imatinib. CNL lacks BCR-ABL1, shows persistent neutrophilia, and has different mutations (like CSF3R), so treatment strategies are different.[]How often will I need blood tests?
At diagnosis and when changing treatment, blood tests may be weekly or even more frequent. Once stable, they may be spaced to monthly or longer. Your schedule is tailored to your disease behavior and therapies.[]Can I live a normal life with CNL?
Many patients can work, study, and enjoy family life, especially during periods of disease stability. However, fatigue, hospital visits, and treatment side effects often require adjustments. Good support and flexible planning help maintain quality of life.[]Should my family members be tested?
Most CNL cases are not inherited, so routine family screening is not usually needed. In rare cases with suspected germline CSF3R mutation, a genetics consultation may be offered.[]What is the prognosis?
CNL has a variable but generally serious course, with median survival in older series measured in years, not decades. Outcomes depend on age, comorbidities, mutation profile, response to therapy, and transplant eligibility.[]Are clinical trials important in CNL?
Yes. Because CNL is so rare, clinical trials and registries are essential to discover new treatments and refine transplant strategies. Participation, when available and safe, contributes to better knowledge for future patients.[]Can diet or supplements cure CNL?
No food or supplement has been proven to cure CNL. Diet and supplements can support general health, but the core of treatment is medical therapy and, in some patients, stem cell transplant. Be cautious of unproven “miracle” cures.[]Is pregnancy possible with CNL?
Some patients can have successful pregnancies, but planning is complex because many CNL drugs are harmful to a fetus. Any pregnancy should be planned in advance with hematology and high-risk obstetrics teams, and some therapies may need to stop or change.[]What should I tell new doctors or dentists?
Always tell any healthcare provider that you have chronic neutrophilic leukemia, list your current medications (including hydroxyurea, ruxolitinib, and any anticoagulants), and mention your most recent blood counts and transplant status, so they can plan safe procedures and avoid risky drug interactions.[]
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.
