SHEDDING LIGHT ON INSOMNIA Dr Larry Lytle Sleep disorders are increasingly becoming a more serious problem. Over 60 million Americans suffer from insomnia or some type of sleep disorder. Diagnostic Sleep Disorder Centers are found in most major cities, many connected with Universities, hospitals and research centers. It is not unusual to have sleep troubles from time to time. People wi
Allinex.orgGraft versus host disease (GvHD) is a complication of allogeneic stem cell transplantation (SCT), in which the cells from the bone marrow or stem cell donor (graft) react to the cells in the patient (host).
This booklet has been written to give you simple, precise definitions of GvHD and to help you to understand the implications of GvHD and its possible treatments. The booklet is designed to compliment the information given by the nurses and doctors, who will be able to give you information specific to you/your child. You should never be afraid to ask questions.
This booklet has a glossary at the back to explain unfamiliar words. Hickman® – a registered trademark of C.R. Bard, Inc. applied to central venous catheter.
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GRAFT vERSUS HOST DISEASE. A GUIDE FOR FAmILIES What is graft versus host disease?
• the conditioning regimes used (pre BmT GvHD can occur following a stem cell transplant whether cells come from bone marrow/peripheral blood or umbilical cord blood. The ‘graft’ is the donor cells and the ‘host’ is the bone marrow transplant (BmT) patient cells.
In GvHD, the donor’s T-cells fight the patient’s organs During and following the transplant drugs are given for and tissue, reducing their ability to work normally.
GvHD treatment. These drugs help towards controlling the donor’s T-cell activity and may prevent/reduce GvHD. T-cells are white cells that can identify “self” (cells This will be discussed with you and your family by your that should be in our bodies) from “non-self” cells that should not be in our bodies for example bacteria and viruses. Once the donated bone marrow begins to grow The main medications used to prevent GvHD are called in the patient’s body the donor’s T-cells become very immunosuppressive drugs in particular a drug called active and identify the patient’s body tissue as ciclosporin. There are other treatments used for GvHD these are discussed later on in the booklet.
T-cells use human leucocyte antigen (HLA) to recognise Types of GvHD
“self” and “non self”. HLA is the inherited genetic material found on the surface of many human cells and Acute GvHD
tissue. The greater the difference between the patient’s This happens up to day 100 after the bone marrow and the donor’s HLA, the quicker and more severe the transplant. This is graded from mild to severe (or grades 1 to 4). Please ask your doctor to explain.
Who gets GvHD?
It is difficult to predict before the transplant exactly This occurs after day 100 and can be limited or extensive.
who will get GvHD and to what extent. When donors are matched to patients, whether related or unrelated, work GvHD can occur in any body part but the most common done in the tissue typing laboratory aims to provide the best match possible. This work can attempt to predict the risk of GvHD. It is worth remembering that most patients will get some GvHD and it is a normal part of There are however some factors which may influence the This booklet will describe each of these separately along Acute GvHD of the skin
Skin GvHD usually starts with a rash. It may be more • female to male sex mismatch of donor and patient, due obvious at certain parts of the day. It often starts on the to female donor T-cells recognising male chromosomes palms of the hands and soles of the feet. The hands and • age of donor, the older the donor the greater the risk feet can become sensitive. The rash may spread, come • if the female donor has had pregnancies Diagnosing acute GvHD of the skin
• exposure to viral infection, particularly Often GvHD of the skin can be diagnosed by looking at the rash. Sometimes your team will get dermatologists (skin doctors) involved for advice, especially to rule out drug reactions. A skin biopsy may be needed to Small to large amounts of diarrhoea may be passed ensure an accurate diagnosis; this allows a small sample several times a day. Often the diarrhoea has a ‘mucus’ of tissue to be collected so it can be examined in the (jelly like) appearance and is green in colour. Sometimes small amounts of blood are present in the diarrhoea. This is caused by the GvHD inflaming the bowel lining and Treating GvHD of the skin
making it delicate. You/your child may experience tummy cramps, pain and sometimes nausea and vomiting with a mild to moderate GvHD (grade 1-2) means the rash may loss of appetite, because attempting to eat often makes cover 50% of the skin surface. Sometimes no treatment is necessary. The skin can become itchy, treatment usually involves emollient creams (special moisturising creams), medication to control the itch and/or steroid Diagnosing acute GvHD of the gut
cream. It may be necessary to add in low doses of Often the symptoms of acute GvHD of the gut and the type of diarrhoea is enough to make a diagnosis. Your stem cell transplantation (SCT) team may also want moderate to severe (grade 3-4) GvHD means the rash you/your child to be assessed by a gastroenterologist covers more than 50% of the skin surface. Treatment will (specialist gut doctor).The gastroenterologist may want involve a combination – intravenous steroid infusions, to view the inside of the bowel with a small camera, (a steroid creams and emollient creams.
procedure called an endoscopy) and take a biopsy of the bowel wall. An accurate diagnosis ensures the correct Other treatments can include additional medication and treatment for acute GvHD of the gut is given.
extracorporeal photochemotherapy or PUvA (see page 10).
Treating acute GvHD of the gut
Your skin can feel uncomfortable at this time. You can Grade 1-2 (mid to moderate) will require low dose steroids (anti-inflammatory drugs) given by mouth or through a drip. Intravenous fluids may be required if the • wearing loose cotton clothing and using cotton bed diarrhoea causes dehydration. Painkillers for tummy cramps and anti-sickness drugs will also be given.
• avoid highly perfumed washing powders and toiletries Grade 2-4 (moderate to severe) will include all of the above treatments plus steroids through a drip • avoid very hot showers and use mild/non perfumed in a higher dose (methylprednisolone) and/or other immunosuppressive agents. As high dose treatment suppresses the immune system antibiotic/antiviral • keeping the skin well moisturised with emollient Sometimes with GvHD the bowel will not tolerate food so you/your child won’t be able to eat. In this case, feeding • care to avoid trauma as the skin may be thin due to • naso-gastric feeding (NG feeding), where a tube is Acute GvHD of the gut
passed through the nose into the stomach, and liquid Acute gut GvHD usually starts with diarrhoea, nausea food enters the stomach directly via the tube and some tummy pain. Remember however, that • total parental nutrition (TPN) is when nutrition is given these symptoms can also be caused by radiotherapy, directly into the bloodstream via the central line, chemotherapy, antibiotics or infection, so a specific diagnosis can sometimes prove difficult.
GRAFT vERSUS HOST DISEASE. A GUIDE FOR FAmILIES Essential measures for caring for you/your child include: Diagnosing acute GvHD of the liver
The SCT team will monitor blood tests to see how well
• good personal hygiene, ensuring that you/your child’s the liver is working. Results will change if liver GvHD happens. If they show that acute GvHD of the liver is • the use of barrier creams around the bottom to prevent occurring it may be necessary to ask hepatologists (specialist liver doctors) to assess any liver damage. A liver scan may be done and a liver biopsy may be taken • regular inspection by the nurses to ensure the skin round the bottom is not broken, damaged or infected • ensuring any sore area is left exposed to fresh air as Treating acute GvHD of the liver
• Low or high dose steroids (anti-inflammatory drugs) • any carer should ensure they wear disposable gloves depending on the grade of acute GvHD of the liver.
when dealing with diarrhoea and thoroughly wash their hands afterwards • medication to help stop itching, which can be given • anti sickness drugs to control nausea and vomiting.
• Blood product support, for example blood and Acute GvHD of the liver
GvHD of the liver affects the small ducts that allow the flow of bile out of the liver. These ducts become inflamed leading to mild, moderate or severe damage. If you/your Chronic GvHD (cGvHD)
child is thought to have early signs of acute GvHD of the cGvHD by definition occurs beyond day 100 from liver, this may only show up as slightly abnormal liver transplantation. It may be a continuation of acute function blood tests. If acute liver GvHD progresses, GvHD or more rarely occur separately. cGvHD can affect almost every organ or system. The most frequently affected areas are the skin, mouth, liver and eyes. It can • jaundice (yellowing of the skin and eyes and darkening also affect the gut (gastrointestinal tract), lungs and How is chronic GVHD diagnosed and treated?
cGvHD can affect more systems than acute GvHD.
• altered bowel actions – stools (poos) may become pale The most common are shown on page 5. Treatment for cGvHD is often the use of steroids with continuing • the clotting mechanism of the blood is made in the cyclosporin or similar drugs such as tacrolimus, though liver. This system can become disturbed in acute GvHD other drugs may be used to help other symptoms. Your of the liver, hence bruising and bleeding can occur SCT team will explain to you how you/your child will be How is chronic GvHD diagnosed and treated?
Signs and symptons
cleansers and regular emollient cream use • dry/flaky especially on knees, elbows and in • hair and eyebrows may have streaks of white • difficulty in breathing following exercise • you/your child may be referred to an ophthalmologist (your specialist eye doctor) GRAFT vERSUS HOST DISEASE. A GUIDE FOR FAmILIES The effect of GvHD on bone marrow
How is alemtuzamab given?
It is given through a drip in hospital, with the first dose Chronic GvHD and the immunosuppressive drug treatment used to treat it, means that you/your child will be at risk of infections. Information on how infection Side effects
can be prevented will be given to you by your SCT team. Reactions are most commonly seen during the first dose, During this time you/your child will not be able to form less frequently with following doses. These may include: a response to certain types of immunisation/vaccination and therefore NO ImmUNISATION / vACCINATION SHOULD BE GIvEN UNTIL INSTRUCTED BY THE SCT Vaginal GvHD
vaginal GvHD is a rare complication that can present as vaginal discomfort and itching or may not be apparent • hypotension (low blood pressure) may also occur until sexual activity commences. It can cause narrowing of the vaginal opening and dryness which may cause pain and/or discomfort during intercourse. If you wish A pre-medication can be given to reduce the severity to have further discussions with you SCT Team as you of these reactions; drugs often used for this include are concerned about this or you wish to have more paracetamol, hydrocortisone or other steroid and an information to give to your child then please contact us. anti-histamine (e.g. chlorphenamine).
Graft versus leukaemia effect
Although GvHD is seen as a complication for some Globulin (ALG/ATG)
children, when children have a stem cell transplant because they have leukaemia or lymphoma, GvHD may actually be useful. As part of the process, donor They selectively destroy T-lymphocytes. They are used T-cells may also recognise host blood cells, including before and during SCT to prevent graft rejection, or to leukaemia, lymphoma cells, and seek to destroy them. So if there are any leukaemic lymphoma cells left after the stem cell transplant, GvHD may destroy these cells How is ATG/ALG given?
and reduce the chance of the disease coming back.
A pre-medication is always given prior to the infusion of ATG/ ALG. It is always given as an intravenous infusion Drugs used in stem cell transplantation
and is infused over a minimum of six hours. Regular (SCT) to prevent/treat GvHD
observations take place throughout the infusion in order The following information on drug treatment is used as a general guide. Your own SCT team will discuss in detail the appropriate medication given to you/your child. Side effects on the administration of ATG/ALG
These drugs are listed in alphabetical order, not their Alemtuzamab
An immunosuppressant used to prevent and treat graft rejection and GvHD, given before the transplant.
very rarely patients can become shocked, causing a low blood pressure, high pulse rate, and breathing difficulties. While ATG/ALG is being used you/your child will be very carefully monitored for these signs.
Particularly used for gut GvHD.
Azathioprine helps to prevent graft rejection by
How is budesonide given?
suppressing the body’s immune or defence system.
Only available in oral capsules. Usually three doses per day are given.
How is azathioprine given?
Available in tablet or injection form.
• Tiredness, muscle weakness
An immunosuppressive drug used to prevent and treat How is ciclosporin given?
Usually twice daily, but can be more or less frequent.
In hospital it will be given through a drip, but changed to tablets or liquid given by mouth when you/your child can tolerate medicines and is free of diarrhoea.
Basiliximab and Dacluzimab
Ciclosporin capsules should be swallowed whole.
They are antibodies used to prevent T-lymphocytes
Ciclosporin liquid can be taken neat or mixed by stirring from reproducing. They are normally used alongside well with water, chocolate powder, or orange/apple juice ciclosporin/mycophenolate mofetil and steroids.
for preferred taste. If diluted with something, this should be done just before the drug is given.
How is it given?
By a 30 minute infusion twice a week on consecutive
days. Both are given by intravenous infusion – Do not use grapefruit juice to dilute ciclosporin or drink grapefruit juice or eat grapefruit within one hour of taking ciclosporin as this interferes with the action of the Side effects
drug. Watch out for mixed fruit juice drinks, for example Five Alive, as they may contain grapefruit juice.
Do not rinse the measure with water or any other liquid. Wipe it clean with a dry tissue between doses.
GRAFT vERSUS HOST DISEASE. A GUIDE FOR FAmILIES How long will I/my child have to take
Applying emollients can be hard work and tedious but is ciclosporin?
worthwhile in preventing skin from drying out.
Blood levels will be checked regularly. This is to make sure that the correct dose of ciclosporin is given to Dry cracked skin can be a route for infection. Your SCT you/your child. You will need to delay giving the dose team will give you advice on how to apply your emollient of ciclosporin until after a blood sample has been taken on days that you/your child has levels measured, as the doctors want to measure the ‘trough’ level. Your SCT How are emollients used?
team will discuss with you exactly how long you/your Emollients are applied externally to the skin. You may be child needs to take it for; this will vary from one month to given a bath oil and/or cream/ointment to apply to your one year, or even longer if severe GvHD develops.
Side effects and precautionary checks
• Kidney and liver function may be affected. Regular It is uncommon to have side effects to emollient creams. blood tests will be taken to check these and determine However some people can become allergic to an ingredient. There are many different emollients. If you • Hypertension (raised blood pressure). Regular blood are concerned speak to your SCT team.
pressure measurements will be taken and drugs to reduce the blood pressure prescribed if needed.
• Tremor or shaky hands. This can be due to high levels Photopheresis is an “extracorporeal photoimmune” of ciclosporin in the blood and if so will reduce as the therapy. Whilst this may sound complicated, broken ciclosporin is reduced and stopped. Some children can develop excess shakiness, slurring of their speech, or unsteadiness on standing or walking even when the Extracorporeal – means outside the body drug level is not high. Please inform your doctor of any of these side effects urgently, as the drug may need to Pheresis – a procedure in which the blood is filtered • Burning hands and feet. This usually only occurs at the Therefore photopheresis is light activated treatment taking place outside the body, where blood cells are • Abdominal pain, nausea, vomiting and diarrhoea.
treated by ultraviolet light as they pass through a special machine. They are then returned to the body where they • Low blood magnesium level. magnesium supplements tend to calm down some of the immune reactions, which can be given to maintain normal levels and your cause GvHD to persist. This is only available in certain dietician can offer advice about foods rich in centres in the UK and patients may need to travel to • Increased hair growth, often around the neck and back and on the arms and legs. This will disappear as the drug is reduced.
Infliximab works by binding to and preventing the activity of a specific protein in the body called tumour necrosis factor alpha (TNF), a chemical that causes inflammation.
Emollients prevent the skin from becoming dry. You would normally be asked to apply the emollients two to three times a day. However, this can be more if your skin How is infliximab given?
Infliximab is given by intravenous infusion.
• increased hair growth (hirsuitism) particularly on • puffy cheeks (a “Cushingoid” appearance – named after Cushing’s disease where your body naturally Methotrexate
• risk of ulcers developing in the gastrointestinal tract Purpose
Used to prevent GvHD by killing the T-cells that are
• higher blood glucose levels – in severe instances Often methotrexate is given with ciclosporin to prevent GvHD. It is given on certain days following the BmT • increased risk of infection – particularly Cmv (often some, or all, of days one, three, five and 11 post- Important: If any of these problems
Occasionally it may be used on a weekly basis after occur you should seek medical advice.
transplant to treat acute GvHD, which is responding Do not stop taking or giving the drug
poorly to steroids, or in an attempt to aid faster reduction of steroid dosage.
How is methotrexate given?
As an intravenous injection through your child’s central
This drug is used to treat and prevent graft rejection and GvHD.
Although methotrexate is given in fairly small doses,
How is mycophenolate mofetil given?
it can cause significant mucositis, gut and liver Two to three times daily via a drip in your arm/Hickman® disturbances and delayed engraftment.
How long will I need to take this medication?
Usually as long as you have symptoms of graft versus
How is it given?
host disease. It may be different from patient to patient.
Often used when ciclosporin and steroids don’t appear methylprednisolone is the intravenous equivalent of to be working or when ciclosporin is not tolerated. may prednisolone and can be given in much higher doses.
be used in conjunction with ciclosporin if you are having a cord stem cell transplant.
Side effects of steroids
These will be discussed with your BmT team, but some
GRAFT vERSUS HOST DISEASE. A GUIDE FOR FAmILIES Rituximab
Rituximab works by killing B-lymphocytes (B-cells), All of these side effects will be monitored and explained How is rituximab given?
very often used in steroid resistance acute graft versus
The side effects of rituximab are generally mild and some of these can be reduced with medicines. Side effects can How is muronomab-CD3 given?
begin during the first dose of the drug and may continue for a few hours afterwards, but are usually milder with Side effects
PUvA is the name given to a skin treatment involving sensitising the skin with psoralens and then exposing it to ultraviolet A rays. Psoralens can be taken by tablet or Used for GvHD prevention and treatment.
applied to the skin in bath. The skin is then exposed to the Uv light.
How is sirolimus given?
PUvA therapy is generally given two to three times per It is given as an oral solution or tablets.
week as an outpatient – for a course of around 6-10 weeks.
• Can drop the blood counts
• TTP (thrombotic thrombocytopenic purpura) Steroids (prednisolone)
• Abnormal kidney function. Regular blood tests will be Steroids lower the production of white cells.
• Abnormal blood electrolytes. Regular blood tests will How is it given?
Prednisolone is available in tablets, dissolvable tablets Thalidomide
This drug is used to treat chronic GvHD.
How is thalidomide given?
may be used to treat GvHD that does not respond to Side effects
How is tacrolimus given?
main side effects are peripheral neuropathy and Tacrolimus should be given orally if possible. Capsules should be swallowed with fluid, preferably water.
Remove the capsule from its blister pack immediately before taking. Once opened the pack must be used within three months.
Tacrolimus may be given via a nasogastric tube if not tolerated by mouth and may be given through a central line if necessary.
Tacrolimus may be given by intravenous infusion over a 24 hour period.
Tacrolimus is given in two doses per day, 12 hours apart and should be taken on an empty stomach for maximum absorption, i.e. one hour before, or two to three hours after a meal.
• Hypertension (raised blood pressure). Regular blood
pressure measurements will be taken and drugs will be given to reduce the blood pressure if required GLOSSARY
Biopsy – the removal of a tiny piece of skin, liver or lining
Immunosuppressive – reducing the effectiveness of the
of the gut to examine it under a microscope. A biopsy IV/Intravenous – a method of giving medication directly
Chromosomes – a thread like structure in the nucleus of
into the vein, either by a drip, central line or an injection.
Hypertension – high (or raised) blood pressure.
Central line – a tube which goes into the child’s chest for
Hypotension – low blood pressure.
Lymphocyte – a white blood cell.
Conditioning – treatment before the bone marrow
transplant used to get rid of the patient’s bone marrow.
Magnesium – an element needed for muscles and
This may involve the use of chemotherapy, radiotherapy Mucus – a slippery, sticky substance.
Dermatologist – a doctor who specialises in the skin.
Nausea – a feeling of the need to be sick.
Diarrhoea – frequent loose stools (poos).
NG feeding/Nasogastric – where a soft, narrow tube is
Emollients – moisturisers.
passed up the nose and into the stomach, through which liquid food and drugs can be given.
Endoscopy – looking inside the body using a very small
Ophthalmologist – a doctor who specialises in the eyes.
Enteric coated – a tablet covered in a sugar coating.
Steroids – a group of drugs used to reduce swelling/
Gastroenterologist – a doctor who specialises in the
stomach and gut.
TPN/Total Parental Nutrition – when the child’s
nutrition is given directly into the bloodstream via the
Genetic – relating to something that is linked to genes.
Gastrointestinal (GI) tract – the mouth, throat, stomach
Tremor – shaking.
and intestines are all from the GI tract.
Hepatologist – a doctor who specialises in the liver.
The RCN represents nurses and nursing, promotes excellence in practice and shapes health policies.
November 2008 second edition
Published by the Royal College of Nursing 0 Cavendish Square London WG 0RN The RCN represents nurses and nursing, promotes excellence in practice and shapes health policies.
La Lettre de MG France RA Mars 2009 COTATION EN CS : LA BELLE VICTOIRE DES GENERALISTES DROMOIS POUR L’EQUITE La Cour d’Appel de Grenoble vient de donner raison à délégation l’honneur de tous les Médecins neuf médecins de MG26 : elle reconnaît le droit aux spécialistes en médecine générale de coter leurs consultations CS. Devant cette victoir