DA – and Ara-C () – for Acute Myeloid Leukaemia (AML)

A Guide for Patients Introduction

In this booklet we focus on DA treatment, the combination of daunorubicin and ara-C, also known as cytarabine, as well as the liposomal formulation of daunorubicin and cytarabine (also known as CPX-351 or Vyxeos). Although some healthcare professionals may use the term ara-C when referring to the generic cytarabine, we will use cytarabine throughout this booklet. Acute myeloid leukaemia (AML) This booklet was compiled is one of the types of leukaemia by Saloua Najjam, PhD. where patients produce too many (Haematology). Thank you to our immature myeloid blast cells. former nurse Shirley Aston, as Blast cells are immature cells well as Nicole Clack, CNS at Guy’s found in the bone marrow which Hospital, for further input and are not fully developed. This insight into this booklet and to type of leukaemia progresses Dr Steve Knapper of University of rapidly. To know more about the Wales, Cardiff for peer reviewing symptoms and diagnosis of AML, the booklet. We are also grateful please view our booklet titled to Julie Quigley for her valuable Acute Myeloid Leukaemia (AML). contribution as a patient reviewer. This booklet was updated by our Patient Information Writer, Isabelle Leach.

If you would like any information on the sources used for this booklet, please email [email protected] for a list of references.

Version 2 Printed: 11/2019 2 www.leukaemiacare.org.uk Review date: 11/2021 In this booklet

Introduction 2

In this booklet 3

About Leukaemia Care 4

What is DA? 6

Who receives DA? 8

How is DA administered? 9

What are the side effects of DA? 12

What happens if DA doesn’t work for me? 17

Glossary 18

Useful contacts and further support 19

Helpline freephone 08088 010 444 3 About Leukaemia Care

Leukaemia Care is a national charity dedicated to ensuring that people affected by blood have access to the right information, advice and support.

Our services has been affected by a blood cancer. A full list of titles – both Helpline disease specific and general Our helpline is available 8:30am information titles – can be – 5:00pm Monday - Friday and found on our website at www. 7:00pm – 10:00pm on Thursdays leukaemiacare.org.uk/support- and Fridays. If you need someone and-information/help-and- to talk to, call 08088 010 444. resources/information-booklets/

Alternatively, you can send Support Groups a message via WhatsApp on Our nationwide support groups 07500068065 on weekdays are a chance to meet and talk 9:00am – 5:00pm. to other people who are going Nurse service through a similar experience. For more information about a We have two trained nurses on support group local to your area, hand to answer your questions go to www.leukaemiacare.org. and offer advice and support, uk/support-and-information/ whether it be through emailing support-for-you/find-a-support- [email protected] or group/ over the phone on 08088 010 444. Buddy Support Patient Information Booklets We offer one-to-one phone We have a number of patient support with volunteers who have information booklets like had blood cancer themselves this available to anyone who or been affected by it in some

4 www.leukaemiacare.org.uk way. You can speak to someone Website who knows what you are going You can access up-to-date through. For more information information on our website, on how to get a buddy call www.leukaemiacare.org.uk. 08088 010 444 or email [email protected] Campaigning and Advocacy Online Forum Leukaemia Care is involved in campaigning for patient well- Our online forum, being, NHS funding and drug www.healthunlocked.com/ and treatment availability. If you leukaemia-care, is a place would like an update on any of for people to ask questions the work we are currently doing or anonymously or to join in the want to know how to get involved, discussion with other people in a email advocacy@leukaemiacare. similar situation. org.uk Patient and carer conferences Patient magazine Our nationwide conferences Our quarterly magazine includes provide an opportunity to inspirational patient and carer ask questions and listen to stories as well as informative patient speakers and medical articles by medical professionals: professionals who can provide www.leukaemiacare.org.uk/ valuable information and support. communication-preferences/

Helpline freephone 08088 010 444 5 What is DA?

DA – Daunorubicin and ara-C (cytarabine) – is a combination of two . Cytarabine is also known as arabinoside (ara-C). Each works in a slightly different way and in the DA regime they are used at the optimum doses to allow the maximum effects in terms of killing cancer cells.

Daunorubicin their growth and reproduction. Cytarabine is commonly used in Daunorubicin, like other the treatment of several acute , is an leukaemias including AML and originally derived from the acute lymphoblastic leukaemia. peucetius bacteria and found to be an effective Key terms to remember: anticancer drug. chemotherapy continues to be Anthracycline – A drug a key component of anticancer originally used as an regimes today. antibiotic, but that was subsequently found to be an Daunorubicin interferes with effective anticancer drug. the DNA and reproduction of white blood cells, including the – A drug that leukaemia cells. It has antimitotic interferes with the (stops ) and cytotoxic necessary for DNA synthesis, (kills cancer cells) activity. and therefore prevents the growth or reproduction of Cytarabine cells. Cytarabine is an antimetabolite Antimitotic – A drug that drug which works by disrupting inhibits mitosis, or cell the DNA of cancer cells, thereby division. slowing or stopping their growth. Cytotoxic – A drug that is Like daunorubicin, cytarabine is toxic to cancer cells and one of a group of drugs known as prevents their growth and cytotoxics. Cytotoxics are drugs reproduction. toxic to cancer cells and prevent

6 www.leukaemiacare.org.uk Helpline freephone 08088 010 444 7 Who receives DA?

The DA combination is If you wish to have given to newly-diagnosed AML further information on patients who are considered to be AML please view our medically fit enough to be treated collection of patient with intensive chemotherapy. information booklets that are available on This is generally patients below our website at www. the age of 60 years and fitter leukaemiacare.org.uk patients aged between 60 and 75 years.

8 www.leukaemiacare.org.uk How is DA administered?

Before starting cytarabine being given in two main ways, either spread over ten treatment days with two doses per day or as Prior to starting day one of your a continuous infusion for seven treatment with DA, your doctor days. These regimens have been will perform a Full Blood Count used for many years and continue (FBC), Liver Function Tests to be the standard induction (LFTs) and Urea and Electrolytes regimen in many countries. (U&Es) tests to confirm your liver and kidneys are functioning In some circumstances, correctly. You may also have an gemtuzumab ozogamicin echocardiogram (ultrasound (also called by the trade name scan of the heart) to assess your Mylotarg) is now added to the heart function prior to starting DA regimen. Mylotarg has a treatment. chemotherapy drug attached to an antibody directed at CD33 on These tests will be performed to the surface of leukaemia cells; ensure that you are medically between one and three doses of fit to start your treatment. Mylotarg can be added to the first Anthracyclines can potentially cycle of DA treatment. have an effect on your heart. For more information on the Usually a central line (PICC line, drug Mylotarg, you can read Hickman line or temporary central our booklet. This is available line) will be inserted, through on our website www. which the chemotherapy can be leukaemiacare.org.uk or can administered. Alternatively, a be ordered by calling 08088 small cannula can be used in your 010 444. arm or hand.

Induction therapy with the DA drug combination given in the UK generally consists of daunorubicin for three days with

Helpline freephone 08088 010 444 9 How is DA administered? (cont.)

Recently, an alternative daunorubicin and cytarabine formulation of DA: daunorubicin (liposomal) that you will receive and cytarabine (liposomal), depends on many factors, (also referred to as CPX-351 or including your height, weight, by its trade name Vyxeos) has general health or any other been approved for use in some health problems. Your doctor will newly-diagnosed AML patients. determine your exact dosage and Vyxeos is the combination of schedule. these two drugs encapsulated in fat-like particles called . If you are well and your blood The liposomes remain in the counts are improving, you patient’s body for longer than will be discharged following the conventional daunorubicin your first treatment of DA. and cytarabine combination, The doctors will review and protect daunorubicin your white cell count (WCC) and cytarabine from being and let you home when the broken down early. This makes neutrophils are greater than daunorubicin and cytarabine 1x109/L. Ask your medical (liposomal) potentially more team if you would like more effective against the cancer cells. information. If, following recovery from your first cycle Daunorubicin and cytarabine of DA or Vyxeos therapy, (liposomal) is given as an it is confirmed that your intravenous infusion over leukaemia is responding to 90 minutes, with antinausea treatment, then it is likely approximately 30 that you will be given a minutes before the infusion second cycle. The second to reduce the risk of nausea cycle of DA may be shorter or vomiting. Three of these (eight days rather than ten; 90-minute infusions are given or three days in the case of over five days (on days one, Vyxeos) and can sometimes three and five). The amount of be given as an outpatient.

10 www.leukaemiacare.org.uk Your chemotherapy nurse will take every precaution possible while administrating DA to avoid any extravasation. This is when chemotherapy leaks out of the vein into the tissues under the skin. In the rare event that this should happen, your nurse will contact a senior member of the medical team such as your haematologist and follow local protocol for dealing with cytotoxic extravasation.

You will have daily routine blood tests while you are in hospital to monitor the effects of the chemotherapy, but tell your nurse if you experience any symptoms that you are worried about.

Helpline freephone 08088 010 444 11 What are the side effects of DA?

This treatment can have serious and possibly life-threatening side effects. Therefore, it is very important that you report any side effects to your doctor straight away.

Chemotherapy is the most ••Perform regular temperature commonly prescribed anticancer checks using a thermometer. treatment. While you are If your temperature exceeds receiving DA treatment, you 37.5°C, contact your doctor and/ may become more vulnerable or hospital team immediately (if to infection. Side effects with you cannot contact them for any the conventional combination reason, go the hospital directly). of daunorubicin and cytarabine Stay extra clean. and the liposomal daunorubicin •• and cytarabine combination are ••If you have a central line (also similar. Symptoms of infection known as a Hickman line), keep like fever, shivering, discomfort the area around it clean and when you pass urine, sweats, dry. This advice should also sore throat, diarrhoea, coughing be followed if you have a PICC or breathlessness should be (Peripherally Inserted Central reported to your doctor or nurse Catheter) line. to prevent them from becoming life-threatening if they are left ••Clean your teeth every day and untreated. check for sores in the mouth or other signs of infection. You can try the following methods to try and minimise the risk of ••If you get injured and have a infection: scratch or cut, make sure you clean it well. ••Hand washing. ••Let your doctor or hospital team ••Avoidance of people with know if you have a sore bottom, infections. or whether it bleeds. If this happens, this could increase

12 www.leukaemiacare.org.uk your risk of infections. occur. Everyone will experience different ••Bruising and bleeding – side effects with DA treatment. It This treatment will reduce is very important that you report the production of platelets any new symptoms to the medical which help the blood clot. Let team so that these symptoms your doctor know if you have can be properly assessed and, if any unexplained bruising or necessary, treated. You will have bleeding, such as nosebleeds, routine blood tests on most days bloodspots or rashes on the while you are in hospital to monitor skin, or bleeding gums. You the effects of chemotherapy. are likely to need platelet transfusions at least twice per Side effects and week until your bone marrow frequencies recovers from the chemotherapy (usually after four to five weeks). There are three frequencies of side effects that you may get with DA ••Anaemia (low number of red treatment: very common (may blood cells – DA chemotherapy affect more than 1 in 10 people), will cause you to become more common (may affect up to 1 in 10 anaemic (reduces the number people) and uncommon (may affect of red blood cells being made in up to 1 in 100 people). the bone marrow). This is often associated with tiredness and Very common side effects breathlessness. Red blood cell ••Infections and low neutrophil transfusions will need to be white blood cell counts with given until your bone marrow fever – These are the most recovers from chemotherapy common effects seen in (after four to five weeks). patients. Because of the low neutrophil white cell counts, ••Hypersensitivity reactions – infections of various types These include skin rashes and such as bacterial infections, itching. pneumonia and sepsis can ••Pain in the muscles and joints.

Helpline freephone 08088 010 444 13 What are the side effects of DA? (cont.)

varies from person to person. Top tips if you experience Your doctor can provide you bleeding: with antinausea • Apply direct pressure on alongside your chemotherapy the bleeding site (this to prevent this. If you continue will apply if it is an open to feel or be sick, tell your area of bleeding skin). nurse and your doctor may increase the dose of antinausea • If you have a nosebleed, medication or change it apply pressure below the completely. bridge of your nose. Top tips for managing nausea: • After applying pressure (where possible), contact • Eat little and often rather your doctor or hospital than large meals. immediately. • Eat foods that appeal to • If you are unable to you rather than forcing control the bleeding, yourself to eat things you go to your hospital do not fancy. immediately. • Eat dry food throughout the day such as toast or Skin changes – DA treatment •• crackers. can cause a skin rash that leaves the skin red and dry and • Try to avoid skipping it might be itchy. Rashes are meals as much as you can. very commonly seen following Vyxeos (CPX-351). • Sip liquids slowly. ••Nausea and vomiting • Avoid foods that have a – Daunorubicin causes strong smell, are overly considerably more nausea sweet, fried or fatty. and vomiting compared to • If you experience vomiting, cytarabine, and this side effect take sips of clear liquids such as water to replace any fluids you have lost.

14 www.leukaemiacare.org.uk ••Effects on the lungs – You may when you feel tired and lacking develop shortness of breath, in energy. First, talk to your a cough, wheezing (fluid in nurse or doctor about it, then the lungs) or a lung infection try to manage it by giving (pneumonia). This is more yourself more rest when needed, common when treatment is learning how to relax and maybe given at higher doses. If this adopting some simple changes is the case, your doctor can to your diet and exercise arrange tests to check your routine. lungs. Tell your doctor or inform your Diarrhoea – As this may be a •• hospital immediately if you sign of infection, you should let develop the following signs your nurse know if this becomes and symptoms of low blood a problem during or after your counts while you are home: treatment. • Fever (a temperature over Mouth problems – Your mouth •• 37.5°C) may become sore or dry, or you may notice small mouth • Infection ulcers during this treatment. Drinking at least two litres of • Nosebleeds on a regular fluids a day and keeping a high basis standard of oral hygiene can • Easy bruising help to reduce the risk of this happening. Your doctor can prescribe a mouthwash for ••Hair loss – This is called you to use during treatment. alopecia and is caused by the Occasionally during treatment, toxicity of chemotherapy. It you may experience a strange can be partial or total, but it is taste, sometimes described as completely reversible as your metallic or bitter that can be hair will grow back when your treated with strongly flavoured treatment is completed. Hair sweets or mints. does not always return to its ••Lethargy/Fatigue – This is pre-chemotherapy state and

Helpline freephone 08088 010 444 15 What are the side effects of DA? (cont.)

can grow back a different colour Serious and potentially life- or style. This hair loss happens threatening side effects gradually usually starting 10 to In a small proportion of patients, 14 days into your first course chemotherapy can result in very of treatment. If you would like severe side effects. Side effects an appointment with the wig that may be serious or potentially service, this can be arranged life-threatening include for you. Ask a member of your infections, hypersensitivity and medical team. bleeding side effects. The medical ••Tumour lysis syndrome – This team caring for you will discuss is an increase in blood uric acid the risk of these side effects with levels which may cause damage you in more detail. to the kidneys, heart or liver. It is Late side effects a result of a very large of cancer cells. Some side effects may only become obvious after a number Uncommon side effects of years. Accordingly, you should ••Numbness and rash in the discuss the details and likelihood hands and feet. of these late side effects with your doctor before starting treatment. ••Heart problems – DA treatment, Your doctor will help you assess especially daunorubicin, may the benefit you receive from the have a toxic effect on the heart. treatment against the risk of This may cause an irregular serious side effects. With some heartbeat, breathlessness drugs there is also a small but or swelling of the legs. You real risk of developing another should inform your nurse or cancer. If any of these problems doctor of any pain in the chest, apply to you, the doctor will palpitations or breathlessness discuss these with you and note that you experience during the this on your consent form. treatment.

16 www.leukaemiacare.org.uk What happens if DA doesn’t work for me?

Approximately 70-85% of In these circumstances, your younger patients will achieve haematologist will be able to complete remission following discuss alternative treatments. DA chemotherapy. The rates of This may involve further intensive remission are somewhat lower chemotherapy, discussion of in older patients and those with options or a switch secondary AML. to less intensive or palliative treatments. Therefore, some patients have a form of disease that is more resistant to treatment.

Leukaemia Care offers nationwide support groups for people affected by a diagnosis of a blood or lymphatic cancer. Visit www.leukaemiacare.org.uk, or call 08088 010 444, to find out more and to find a group near you.

Helpline freephone 08088 010 444 17 Glossary

Anthracycline injection site at any time please let your doctor or nurse know An anthracycline is a drug straightaway. originally used as an antibiotic, but it was subsequently found to Induction Therapy be an effective anticancer drug. Examples of anthracycline are Treatment intended to kill the daunorubicin and . majority of the leukaemia blasts in the blood and bone marrow Antimitotic and to restore normal blood cell production. An antimitotic drug is a drug that inhibits mitosis, or cell division. Leukaemia Bilirubin A group of that usually An orange-yellow substance made begin in the bone marrow during the normal breakdown and result in high numbers of of red blood cells. A raised blood abnormal blood cells. These cells bilirubin level can lead to jaundice are not fully developed and are and may be an indication of called blasts or leukaemia cells. problems with the liver which Depending on the type of blood excretes bilirubin. cell involved, there are different types of leukaemia with varying Creatinine characteristics, such as being A waste product in the body acute (develops quickly) or that comes from normal wear chronic (develops slowly). and tear on muscles. High levels Tumour Lysis Syndrome of creatinine in the body may indicate poor function of the The rapid destruction of a large kidneys as they excrete creatinine. number of white blood cells that can increase blood uric acid levels Cytotoxic which may cause damage to the Drugs that are toxic to cancer kidneys, heart or liver. cells and prevent their growth and Prophylaxis reproduction. Treatment given, or action taken, Extravasation to prevent disease. Accidental leakage of certain medicines into the body from an IV drip in the vein. If you develop redness, soreness or pain at the

18 www.leukaemiacare.org.uk Useful contacts and further support

There are a number of helpful Bloodwise sources to support you during Bloodwise is the leading charity your diagnosis, treatment and into the research of blood cancers. beyond, including: They offer support to patients, ••Your haematologist and their family and friends through healthcare team patient services. ••Your family and friends 020 7504 2200 ••Your psychologist (ask your www.bloodwise.org.uk haematologist or CNS for a Cancer Research UK referral) Cancer Research UK is a leading Reliable online sources, •• charity dedicated to cancer such as Leukaemia Care research. Charitable organisations •• 0808 800 4040 There are a number of www.cancerresearchuk.org organisations, including ourselves, who provide expert Macmillan advice and information. Macmillan provides free practical, Leukaemia Care medical and financial support for people facing cancer. We are a charity dedicated to 0808 808 0000 supporting anyone affected by www.macmillan.org.uk the diagnosis of any blood cancer. We provide emotional support Maggie’s Centres through a range of support Maggie’s offers free practical, services including a helpline, emotional and social support patient and carer conferences, to people with cancer and their support group, informative families and friends. website, one-to-one buddy service and high-quality patient 0300 123 1801 information. We also have a nurse www.maggiescentres.org on our help line for any medical Citizens Advice Bureau (CAB) queries relating to your diagnosis. Offers advice on benefits and Helpline: 08088 010 444 financial assistance. www.leukaemiacare.org.uk [email protected] 08444 111 444 www.adviceguide.org.uk

Helpline freephone 08088 010 444 19 Leukaemia Care is a national charity dedicated to providing information, advice and support to anyone affected by a blood cancer.

Around 34,000 new cases of blood cancer are diagnosed in the UK each year. We are here to support you, whether you’re a patient, carer or family member.

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