Hyper-CVAD is used to treat some types of non-Hodgkin lymphoma (NHL) and acute lymphoblastic leukaemia (ALL).
Hyper-CVAD is used to treat some types of non-Hodgkin lymphoma (NHL) and acute lympho-blastic leukaemia (ALL). It is best to read this information with our general information about chemotherapy and the type of cancer you have.
Hyper is short for hyperfractionated. This means you have more than one treatment of the same drug in a day. The letters CVAD stands for the initials of combination of some of the drugs used:
Hyper-CVAD treatment also includes two other chemotherapy drugs:
This means it is sometimes called hyper-CVAD/MTX-cytarabine. But most people call it hyper-CVAD. Hyper-CVAD is sometimes given with a targeted therapy called rituximab. This treatment is called R-hyper-CVAD.
Your doctor will talk to you about this treatment and its possible side effects before you agree (consent) to have treatment.
You will be given hyper-CVAD during a stay in hospital or in the chemotherapy day unit. A chemotherapy nurse will give it to you.
During treatment, you usually see a cancer doctor, a blood doctor (haematologist), a chemotherapy nurse or a specialist nurse and a specialist pharmacist. This is who we mean when we mention doctor or nurse in this information.
Before or on the day of treatment, a nurse or person trained to take blood (phlebotomist) will take a blood sample from you. This is to check that your blood cells are at a safe level to have chemotherapy.
You will see a doctor or nurse before you have chemotherapy. They will talk to you about your blood results and ask you how you have been feeling. If your blood results are okay, the pharmacist will prepare your chemotherapy. Your nurse will tell you when your treatment is likely to be ready.
Your nurse usually gives you anti-sickness (anti-emetic) drugs before the chemotherapy.
You have the chemotherapy drugs as a drip (intravenous infusion). They can be given through:
- a short thin tube the nurse puts into a vein in your arm or hand (cannula)
- a fine tube that goes under the skin of your chest and into a vein close by (central line)
- a fine tube that is put into a vein in your arm and goes up into a vein in your chest (PICC line).
The nurse will give you the following drugs into your cannula, or central or PICC line separately:
- Cyclophosphamide is given as a drip over 2 hours.
- Vincristine is given as a drip over 10 minutes.
- Doxorubicin (a red fluid) is given as a drip. The time over which you have it may vary between hospitals.
- Dexamethasone is given as tablets or an injection into your line.
- Methotrexate is given as a drip over 24 hours.
- Cytarabine is given as a drip over 2 hours.
You have methotrexate and cytarabine on a different day from the other chemotherapy drugs.
Sometimes methotrexate and cytarabine are given by injection into the fluid around the spinal cord (intrathecally).
Chemotherapy by injection into the spinal fluid
When chemotherapy is injected into the spinal fluid, it is called intrathecal chemotherapy. Your cancer doctor or nurse will tell you more about this.
Intrathecal chemotherapy is when chemotherapy is given into the fluid around the spinal cord during a procedure called a lumbar puncture. A lumbar puncture can be done in an outpatients department or on a ward at the hospital.
Your course of chemotherapy
You usually have a course of several cycles of treatment over a few months Each cycle of hyper-CVAD lasts 21 days.
You usually have hyper-CVAD as two different combinations or schedules of treatment. They are called schedule A and B. You will have 4 cycles of each schedule in a repeating pattern of A then B.
If you have hyper-CVAD before a stem cell transplant, you usually only have 2 cycles of each schedule.
If you have hyper-CVAD with rituximab your treatment plan may be different to the schedules below.
Your nurse or doctor will talk to you about how the treatment will be given. They may give you a copy of a treatment plan to take home with you.
Schedule A (cycles 1, 3, 5 and 7)
You have 2 separate drips (infusions) of cyclophosphamide. The second drip is given 12 hours after the first. You will have fluids through a drip before and after cyclophosphamide. You may also have a drug called mesna (Uromitexan®) to prevent bladder irritation.
You also start taking dexamethasone (steroid) tablets. You take them for 4 days (days 1-4).
You have 2 infusions of cyclophosphamide again, 12 hours apart.
You have the cyclophosphamide treatment again.
You have vincristine and doxorubicin as a drip. You can usually go home the day after it finishes.
Days 5 to 10
You do not have any treatment.
You have vincristine again, usually in the chemotherapy day unit. You also start taking dexamethasone tablets for 4 days (days 11 to 14).
Days 15 to 21
You do not have any treatment. This is the last week in the cycle. Your next cycle will be Schedule B.
Schedule B (cycles 2, 4, 6 and 8)
You have methotrexate as a drip over 24 hours.
You usually have a drug called leucovorin (folinic acid) as a drip. This helps to reduce the side effects of methotrexate. You have it regularly until the methotrexate is out of your system. You also have 2 infusions of cytarabine, 12 hours apart.
You have 2 more infusions of cytarabine. You can usually go home after this if your methotrexate levels are okay.
Days 4 to 21
You do not have any treatment. This completes the cycle of hyper-CVAD. Your next cycle will be schedule A again.
We explain the most common side effects of this treatment here. We also include some less common side effects. You may get some of the side effects we mention, but you are unlikely to get all of them.
You may also have some side effects that we have not listed here. Always tell your doctor, nurse or pharmacist about any side effects you have.
Your doctor can give you drugs to help control some side effects. It is important to take them exactly as your nurse or pharmacist explains. This means they will be more likely to work for you. Your nurse will give you advice about managing your side effects. After your treatment is over, most side effects start to improve.
Serious and life-threatening side effects
Some cancer treatments can cause severe side effects. Rarely, these may be life-threatening. Your cancer doctor or nurse can explain the risk of these side effects to you.
Contact the hospital
Your nurse will give you telephone numbers for the hospital. If you feel unwell or need advice, you can call them at any time of the day or night. Save these numbers in your phone or keep them somewhere safe.
We cannot list every side effect for this treatment. There are some rare side effects that are not listed. You can visit the electronic Medicines Compendium (eMC) for more detailed information.
Some people have an allergic reaction while having this treatment. Signs of a reaction can include:
- feeling hot or flushed
- a skin rash
- feeling dizzy
- a headache
- feeling breathless or wheezy
- swelling of your face or mouth
- pain in your back, tummy or chest.
Your nurse will check you for signs of a reaction during your treatment. If you feel unwell or have any of these signs, tell them straight away. If you do have a reaction, it can be treated quickly.
Sometimes a reaction happens a few hours after treatment. If you develop any signs or feel unwell after you get home, contact the hospital straight away.
The drug leaks outside the vein
The drug may leak outside the vein. If this happens it can damage the surrounding tissue. This is called extravasation. Extravasation is not common but if it happens it is important to treat it quickly. Tell your nurse straight away if you have any stinging, pain, redness or swelling around the vein.
You may suddenly feel warm and your face may get red while the doxorubicin is being given. This should only last a few minutes.
Risk of infection
This treatment can reduce the number of white blood cells in your blood. These cells fight infection. If the number of white blood cells is low, you are more likely to get an infection. A low white blood cell count is sometimes called neutropenia.
An infection can be very serious when the number of white blood cells is low. It is important to get any infection treated as soon as possible. Contact the hospital straight away on the 24-hour contact number you have been given if:
- your temperature goes over 37.5°C (99.5°F)
- you suddenly feel unwell, even with a normal temperature
- you have symptoms of an infection
- your temperature goes below 36°C (96.8°F).
Symptoms of an infection include:
- feeling shivery and shaking
- a sore throat
- a cough
- needing to pass urine (pee) a lot, or discomfort when you pass urine.
It is important to follow any specific advice your cancer treatment team gives you.
The number of white blood cells will usually return to normal before your next treatment. You will have a blood test before having more treatment. If your white blood cell count is low, your doctor may delay your treatment for a short time, until your cell count increases.
You may be given a drug called G-CSF. This encourages the body to make more white blood cells. You have it as a small injection under the skin.
Bruising and bleeding
This treatment can reduce the number of platelets in your blood. Platelets are cells that help the blood to clot.
If the number of platelets is low, you may bruise or bleed easily. You may have:
- bleeding gums
- heavy periods
- blood in your urine (pee) or stools (poo)
- tiny red or purple spots on the skin that may look like a rash.
Tell your doctor if you have any unexplained bruising or bleeding. You may need a drip to give you extra platelets. This is called a platelet transfusion.
Anaemia (low number of red blood cells)
Chemotherapy can reduce the number of red blood cells in your blood. Red blood cells carry oxygen around the body. If the number of red cells is low, this is called anaemia. You may have symptoms such as:
- pale skin
- lack of energy
- feeling breathless
- feeling dizzy and light-headed.
Tell your doctor or nurse if you have these symptoms.
If you are very anaemic, you may need a drip to give you extra red blood cells. This is called a blood transfusion.
Sometimes doctors prescribe a drug called erythropoietin. This helps the body to make more red blood cells. It is given as an injection under the skin. But it is more common to have a blood transfusion for anaemia.
Your doctor will give you anti-sickness drugs to help prevent or control sickness during your treatment. Take the drugs exactly as your nurse or pharmacist tells you. It is easier to prevent sickness than to treat it after it has started.If you feel sick, take small sips of fluids often and eat small amounts regularly. It is important to drink enough fluids. If you continue to feel sick, or are sick (vomit) more than once in 24 hours, contact the hospital as soon as possible. They will give you advice. Your doctor or nurse may change the anti-sickness drug to one that works better for you.
Loss of appetite
This treatment can affect your appetite. Do not worry if you do not eat much for a day or two. But if your appetite does not come back after a few days, tell your nurse or dietitian. They will give you advice. They may give you food or drink supplements.
Feeling tired is a common side effect of this treatment. It is often worse towards the end of treatment and for some weeks after it has finished. Try to pace yourself and plan your day so you have time to rest. Gentle exercise, like short walks, can give you more energy.
If you feel sleepy, do not drive or use machinery.
Muscle or joint pain
You may get pain in your muscles or joints for a few days after treatment. If this happens, tell your doctor so they can give you painkillers. Tell them if the pain does not get better. If you have painkillers you would like to use at home, check with your doctor, nurse or pharmacist whether they are suitable for you.
If you have muscle or joint pain, try:
- placing a heat pad or covered hot water bottle against the painful area
- taking warm baths
- planning your activities to include regular rests.
You usually lose all the hair from your head. You may also lose your eyelashes and eyebrows, as well as other body hair. Hair loss usually starts after your first or second treatment.
Your nurse can talk to you about ways to cope with hair loss. There are ways to cover up hair loss if you want to. Your scalp may be sensitive. It is important to cover your head to protect your skin when you are out in the sun.
Hair loss is usually temporary. Your hair will usually grow back after treatment finishes.
Sore mouth and throat
This treatment may cause a sore mouth and throat. You may also get mouth ulcers. This can make you more likely to get a mouth or throat infection. Use a soft toothbrush to clean your teeth or dentures in the morning, at night and after meals.
If your mouth or throat is sore:
- tell your nurse or doctor – they can give you a mouthwash or medicines to help
- try to drink plenty of fluids
- avoid alcohol, tobacco, and foods that irritate your mouth and throat.
Sucking ice chips may sometimes help relieve mouth or throat pain. But if you are having radiotherapy to the head or neck, do not suck on ice. It can cause damage.
This treatment may cause severe diarrhoea. Diarrhoea means passing more stools (poo) than is usual for you, or having watery or loose stools. If you have a stoma, it will be more active than usual.
Your hospital team may give you anti-diarrhoea drugs to take at home.
If you have diarrhoea or a mild increase in stoma activity:
- follow any advice from your cancer team about taking anti-diarrhoea drugs
- drink at least 2 litres (3½ pints) of fluids each day
- avoid alcohol, caffeine, milk products, high-fat foods and high-fibre foods.
Contact the hospital straight away if:
- you have diarrhoea at night
- you have diarrhoea more than 4 times in a day
- you have a moderate or severe increase in stoma activity
- the anti-diarrhoea drugs do not work within 24 hours.
You may need to go to hospital to have fluids through a drip.
This treatment can cause constipation. Constipation means that you are not able to pass stools (poo) as often as you normally do. It can become difficult or painful. Here are some tips that may help:
- Drink at least 2 litres (3½ pints) of fluids each day.
- Eat high-fibre foods, such as fruit, vegetables and wholemeal bread.
- Do regular gentle exercise, like going for short walks.
If you have constipation, contact the hospital for advice. Your doctor can give you drugs called laxatives to help.
Urine (pee) changing colour
Cyclophosphamide may irritate your bladder and cause discomfort when you pass urine (pee). You will be given fluids through a drip to help prevent this. Some people may also be given a drug called mesna as a drip (infusion) or tablets.
Make sure you drink plenty of fluids during the 24 hours following chemotherapy. Try to drink at least 2 litres (3 ½ pints).
It is also important to empty your bladder regularly and to try to pass urine as soon as you feel the need to go. Contact the hospital straight away if you:
- find it difficult to pass urine
- feel any discomfort or stinging when you pass urine
- notice blood in your urine.
Tummy pain and indigestion
Steroids can irritate the stomach lining. Let your nurse or doctor know if you have pain in your tummy or indigestion. They can give you drugs to help. Taking steroids with food can help to protect your stomach.
Raised blood sugar levels
Steroids can raise the levels of sugar in your blood. Your nurse will check your blood regularly for this. They may also test your urine for sugar. Symptoms of raised blood sugar include:
- feeling thirsty
- needing to pass urine (pee) more often
- feeling tired.
Tell your doctor or nurse if you have these symptoms.
If you have diabetes, your blood sugar levels may be higher than usual. Your doctor will talk to you about how to manage this. You may need to adjust the dose of your insulin or diabetes tablets.
Steroids can make you feel more hungry than usual and you may gain weight. Your appetite will go back to normal when you stop taking them. If you are worried about gaining weight, talk to your doctor or nurse.
Hyper-CVAD may affect your skin. Your doctor or nurse can tell you what to expect. If your skin feels dry, try using an unperfumed moisturising cream every day. Hyper-CVAD can cause a rash, which may be itchy.
During, and for some months after treatment, you will be more sensitive to the sun. This means that your skin may burn more easily. If you are out in the sun, use a sun cream with a high sun protection factor (at least SPF 30) to protect your skin. Cover up with clothing and a hat. Your skin may darken. But it will return to its normal colour after you finish treatment. If you have had radiotherapy, the area that was treated may become red or sore.
Always tell your doctor or nurse about any skin changes. They can give you advice and may give you creams or medicines to help. Any changes to your skin are usually temporary and improve when treatment finishes.
This treatment can affect your nails. They may grow more slowly or break more easily. You might notice ridges or white or dark lines across your nails. Sometimes nails can become loose or fall out. When treatment finishes, any changes usually disappear as the nails grow out.There are things you can do to look after your nails:
- Moisturise your nails and cuticles regularly.
- Keep your nails clipped short.
- Wear gloves to protect your nails when you are doing things in the house or garden.
- Keep your hands and nails clean to help avoid infection, but avoid bathing in very hot water.
- Do not use false nails, gels or other acrylics during this treatment, as they may increase the risk of infection.
- It is fine to wear nail varnish, but try to use a water-based polish. Avoid using harsh chemicals, such as acetone, when taking off the polish.
- If your toenails are affected, wear well-fitted shoes to cushion them.
Tell your doctor or nurse if you notice changes to your nails. They can give you advice or arrange for you to see a podiatrist for foot care advice if needed.
Numb or tingling hands or feet (peripheral neuropathy)
This treatment may affect the nerves, which can cause numb, tingling or painful hands or feet. You may find it hard to fasten buttons or do other fiddly tasks.
Tell your doctor if you have these symptoms. They sometimes need to lower the dose of the drug. The symptoms usually improve slowly after treatment finishes. But for some people they may never go away. Talk to your doctor if you are worried about this.
Build-up of fluid
Steroids may cause your ankles and legs to swell. This is because of fluid building up. Tell your doctor or nurse if fluid builds up. If your ankles and legs swell, it can help to put your legs up on a foot stool or cushion. The swelling gets better after the treatment ends.
This treatment may make your eyes feel sore, red and itchy. This is called conjunctivitis. Your doctor will prescribe eye drops to help prevent this. It is important to use these as you are told to.
This treatment may also make your eyes more sensitive to light and cause blurry vision. If you have pain or notice any change in your vision, always tell your doctor or nurse.
Effects on the kidneys
This treatment can affect how your kidneys work. This is usually mild and goes back to normal after treatment finishes. You will have blood tests to check how well your kidneys are working. Tell your doctor or nurse if you have blood in your urine (pee) or you are passing urine less than usual.
It is important to drink at least 2 litres (3½ pints) of non-alcoholic fluid each day to help protect your kidneys.
Changes in the way the liver works
Hyper-CVAD may affect how your liver works. This is usually mild and goes back to normal after treatment. You will have blood tests to check how well your liver is working.
Mood and behaviour changes
Steroids can affect your mood. You may feel anxious or restless, have mood swings or have problems sleeping. Taking your steroids in the morning may help you to sleep better. Tell your doctor or nurse if you have any of these side effects.
Tumour lysis syndrome (TLS)
This treatment may cause cancer cells to die and break down very quickly. When cancer cells break down, it can lead to a sudden release of chemicals into the blood. This is called tumour lysis syndrome (TLS).
Your kidneys can usually keep these chemicals in balance, but they might not be able to cope with very large amounts. The chemical imbalance can affect how well your kidneys work and cause problems with your heart rhythm.
You will have regular blood tests to check the levels of these chemicals.
If you are at risk of TLS, your doctor can give treatment to help prevent it. You may have:
- extra fluids through a drip
- medicines such as rasburicase or allopurinol
Drinking at least 2 litres (3½ pints) of fluid a day will also help.
Sore and red palms of hands and soles of feet
You may get sore and red palms of hands and soles of feet. The skin may also begin to peel. This is called palmar-plantar or hand-foot syndrome. It usually gets better after treatment ends.
Tell your doctor or nurse about any changes to your hands or feet. They can give you advice and prescribe creams to improve any symptoms you have. It can help to:
- keep your hands and feet cool
- moisturise your hands and feet regularly
- avoid tight-fitting socks, shoes and gloves.
Effects on the lungs
This treatment can cause changes to the lungs. Tell your doctor if you develop:
- a cough
You should also tell them if any existing breathing problems get worse. You may have tests to check your lungs.
Effects on the heart
This treatment can affect how the heart works. You may have tests to see how well your heart is working. These may be done before, during and after treatment.
If the treatment is causing heart problems, your doctor may change the type of treatment you are having.Contact your doctor straight away on the 24-hour number the hospital has given you if you have any of these symptoms during or after treatment:
- pain or tightness in your chest
- changes to your heartbeat.
Other conditions can cause these symptoms, but it is important to get them checked by a doctor. If you cannot get through to your doctor, call the NHS urgent advice number on 111.
Effects on the nervous system
Rarely, hyper-CVAD can affect the nervous system. Tell your doctor or nurse straight away if you notice that you feel:
It is important not to drive or operate machinery if you notice these effects.
Rarely, hyper-CVAD can cause seizures (fits). Your doctor or nurse will explain more about this.
Side effects of intrathecal hyper-CVAD
The side effects of intrathecal hyper-CVAD may be different from those mentioned here. Your doctor or nurse will talk to you about this.
When methotrexate and cytarabine are given this way, it can cause:
- blurred vision
- loss of balance for a few hours.
Tell your nurse or doctor straight away if you have any of these.
It is important to tell your doctor or nurse straight away if you feel ill or have severe side effects. This includes any we do not mention here.
Blood clot risk
Cancer and some cancer treatments can increase the risk of a blood clot. Symptoms of a blood clot include:
- throbbing pain, redness or swelling in a leg or arm
- suddenly feeling breathless or coughing
- sharp chest pain, which may be worse when you cough or take a deep breath.
If you have any of these symptoms, contact the hospital straight away on the 24-hour contact number you have been given. If you cannot get through to your doctor, call the NHS urgent advice number on 111.
A blood clot is serious, but it can be treated with drugs that thin the blood (anticoagulants). Your doctor or nurse can give you more information.
You can help reduce the risk of developing a blood clot by:
- staying active during treatment
- drinking plenty of fluids, especially water.
You may be given anticoagulants to help prevent a clot.
Other medicines and food
Some medicines can affect chemotherapy or be harmful when you are having it. This includes medicines you can buy in a shop or chemist. Tell your cancer doctor about any medicines you are taking, including vitamins, herbal drugs and complementary therapies.
It is important to avoid eating grapefruit or drinking grapefruit juice during your course of chemotherapy. This is because a chemical in grapefruit can affect how well the treatment works or can make side effects worse.
Vaccinations can reduce your risk of getting certain infections. Your doctor or nurse may talk to you about having vaccinations.
Doctors usually recommend that people with cancer have a flu vaccination and a coronavirus vaccination. These are both inactivated vaccinations that can help reduce the risk of infection. People with weak immune systems can have these, as they are not live vaccinations.
If your immune system is weak, you need to avoid live vaccinations. This is because they can make you unwell. Live vaccines, such as shingles, contain a very weak version of the illness they are vaccinating you against. Your cancer doctor or GP can tell you more about live and inactivated vaccinations.
Your doctor will advise you not to:
- get pregnant while having this treatment and for at least 1 year afterwards
- make someone pregnant while having this treatment and for at least 6 months afterwards.
This is because the drugs may harm the developing baby. It is important to use effective contraception.
You are advised not to breastfeed while having this treatment, or for some time after treatment finishes. This is because the drugs could be passed to the baby through breast milk.
Your doctor or nurse can give you more information.
Some cancer drugs can affect whether you can get pregnant or make someone pregnant.
If you are a woman, your periods may become irregular or stop. This may be temporary, but for some women it is permanent. Your menopause may start sooner than it would have done.
If you have sex in the first few days after this treatment, you should use barrier protection such as a condom or dental dam. This will protect your partner if any of the drug is in your semen or vaginal fluids.
Medical and dental treatment
If you need medical treatment for any reason other than cancer, always tell the doctors and nurses you are having cancer treatment. Give them the contact details for your cancer doctor so they can ask for advice.
If you think you need dental treatment, talk to your cancer doctor or nurse. Always tell your dentist you are having cancer treatment.
This information has been written, revised and edited by Macmillan Cancer Support’s Cancer Information Development team. It has been reviewed by expert health professionals and people living with cancer.
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