After Your Islet Transplant

Now what?

Immediately after transplant you will continue to take some insulin, although usually this is at much lower doses than before transplant. Your insulin requirements will change week to week, and the transplant team will help you to make adjustments, so you will need to monitor your blood glucose and insulin use very carefully.

It is important to remember that the islets will take several weeks to settle into their new home in your liver. We call this process  engraftment. During this period we will ask you to keep tour blood glucose levels within quite a tight range so the islets are not overworked. This is similar to when you plant a crop. Not every seed that you put in the ground will grow into a plant. However, if you prepare your soil and feed and water the seeds, you increase your chance for a good harvest.

This is the same with an islet transplant: if you take good care in this initial time period, you have a better chance of good islet function. This includes watching your diet and living a healthy balanced lifestyle.

What about the immune system?

Following discharge you must help with the care of the islets. You will require immunosuppressive drugs for as long as the islets are functioning. If you fail to take the drugs your body will destroy the islets by a process called rejection.

What is rejection?

Rejection is the process when transplanted cells are destroyed by the body's immune system. Normally the immune system is there as a natural defense against bacteria and viruses to prevent infections. Your immune system will identify that your transplanted islet tissue is "foreign" to you and will then activate processes to attack and destroy them. 

It is not easy to tell if you are rejecting your new islet tissue. If your islets are rejected they will no longer produce insulin and your blood sugars will run high. Unfortunately, by the time this happens it will probably be too late to reverse the rejection and the damage may be permanent.

It is therefore very important to prevent rejection by maintaining the levels of anti-rejection (immunosuppression) drugs in their target range.

How do we prevent your body from rejecting the islet cells?

We use medications to dampen down the activity of the immune system. We suppress your immune system just enough so that you do not reject your islet tissue, but still leave it active enough to deal with common infections.

These medications are called immunosuppressants. The drugs we use most commonly for maintenance are tacrolimus (Prograf®) and mycophenolate mofetil (CellCept®). Around the time of transplant we use other drugs, including daclizumab (Zenapax®), Thymoglobulin® and Etanercept®. These drugs work together to attack the immune system from several directions to stop it from being activated. Generally you will take two immunosuppressant drugs to prevent rejection. Your nurse coordinator and a transplant physician will explain these medications to you. Other drugs or antibodies may be used to prevent rejection depending on results of future studies.

We must monitor blood levels of your immunosuppressive drugs closely to make sure you do not have too little of these drugs in your system (so that you do not reject your islet tissue) or have too much which could cause side effects. Once you are at a stable level the frequency of your monitoring will be decreased.

How does the immune system work?

In very simple terms, white blood cells function to identify and neutralize foreign cells and particles. Some white blood cells mainly function to identify invading cells and call for reinforcements; these reinforcements are the killer cells which destroy the foreign cells. After any encounter like this, the immune system remembers the identity of these invaders so it can deal with future attacks much more quickly.

This provides us with immunity. As a general example, when you have a flu shot, a live (but weak) influenza (flu) vaccine is injected into the body and the immune system will fight it off and therefore recognize it more quickly in the future. The immune system protects us from viruses, bacteria, fungus and cancer.

Common side effects of all immunosuppressant medications
Every medication causes alterations in your body. Some of these alterations are the reason that you take the medication. However, each medication can cause undesirable changes known as side effects, which can vary in their seriousness and intensity. We are providing you with information about all the possible side effects that we are aware of.

You are not expected to get all the side effects that are listed for each drug. In fact, you may not experience any side effects at all. However, it is important that you know what to expect should they occur and how to manage them. In addition, it is important to note that you may develop some side effects that are not yet recognized. We learn new information with each transplant and from each patient. 

General decreased ability to fight infection

Specific Drugs

Tacrolimus (Prograf®) — Tacrolimus acts directly on white blood cells to reduce their ability to identify foreign cells.

How to take

Side effects

Sirolimus (Rapamycin®, Rapamune®) — Sirolimus is a relatively new medication that is used to prevent rejection. It has been reported to have anti-tumor activity. It decreases the ability of your body to identify invading cells .

How to take

Side effects

Daclizumab (Zenapax®) — Daclizumab is a genetically engineered antibody that inactivates the building blocks of the immune system. This protection for your islet tissue lasts approximately four months, decreasing the risk of acute rejection at the most vulnerable time period following the transplant procedure.

How to take

Daclizumab is given intravenously in 50 to 100 ml of normal saline over fifteen to thirty minutes, once before transplant and once four to five days after transplant. This is administered in the Medical Outpatient Unit of the University Hospital. Pulse and blood pressure are taken pre-infusion, post-infusion and fifteen minutes post-infusion.

Side effects

There are no known side effects directly linked to daclizumab, but there may be side effects due to the administration of a foreign protein including itching, rash, fevers, shortness of breath, back or flank pain or low blood pressure.

Three serious side effects have occurred with patients taking daclizumab - shortness of breath, low oxygen levels in the blood and renal vein thrombosis (clotting) - however, these could also be due to many other underlying factors and therefore are not proven to be caused by Zenapax® itself.

At our centre, most patients have not experienced any major side effects from this drug. However, some have experienced fatigue after the daclizumab infusion.

As we gather new information, and new medications become available, there may be other immunosuppressant medications that will be prescribed to you. Other medications that have been used for some patients include Thymoglobulin® and CellCept® (mycophenolate mofetil).

Anti-thymocyte Globulin (Rabbit) (Thymoglobulin®) Anti-thymocyte Globulin (ATG) is a medication which modifies your immune system, so your body will accept the islet tissue. It is a mixture of antibodies that recognizes key receptors on T-cells (part of the immune system, which are responsible for attacking and rejecting foreign substances within the body) ATG destroys these T-cells and decreases the risk of rejection. The drug remains active in your system for days to weeks following treatment. This medication has been used extensively in kidney, liver, heart, lung, bowel and bone marrow transplantation.

How to take

ATG is given intravenously in the hospital at the time of transplant, as a continuous infusion.

Side effects

As with any medication, use of ATG can result in serious infusion-related reactions which could be life threatening. You will be given medications prior to infusion to decrease the risk of the infusion-related reaction.

Common side effects associated with ATG include fever and chills. To a lesser extent, people have also experienced diarrhea, headache, aches/pains, nausea, swelling of extremities, shortness of breath, weakness, increased pulse and increased blood pressure.

Mycophenolate Mofetil (CellCept®) —CellCept® is a medication used to prevent your body from rejecting your transplanted islets. It does this by lowering the activity of the immune system.

How to take

Side effects

Call your doctor right away if you notice any of these side effects:

Infection is a common complication after transplantation. As you have already learned, your suppressed immune system has less ability to fight the organisms in your body that cause infection. Your immune system attacks any organisms that are identified as not belonging in the body. When the immune system is unable to control an organism, infection occurs. We use medications to prevent infection (prophylaxis) and to treat infections (therapy). You will know when you have an infection. When the body is fighting an infection, there is cell damage and there are chemicals released that cause symptoms. These symptoms are signs that your immune system is fighting an organism, so it is important to know what to look for.

Increased temperature (higher than 38.5C), chills and/or shivering, pain, swelling, redness and heat in any area of the body. Feeling very tired, achy or weak. Vomiting or diarrhea. Frequent, painful urination or change in color, amount or odor of your urine. Cold symptoms, green sputum (phlegm). Sores on your lips, mouth or face.

Bacteria, viruses and other organisms are everywhere: on your skin, on surfaces you touch, in the air you breathe and in the food you eat. They also live in our bodies. However, only a small number of organisms cause illness. Organisms can enter your body from an injury to your skin or through body cavities such as your nose or mouth that are exposed to the environment. That is why good hygiene is an important way to prevent infection.

Hand washing is the most effective way of reducing your risk of infection. Avoiding contact with those who are ill is another common sense way to stay healthy. Ensuring your body is healthy by eating a good diet, getting adequate rest, exercising regularly and having regular dental care also help prevent infection.

Even with our best efforts to stay healthy, we still get infections. Sometimes our immune systems need help in keeping infection under control. The following is a description of the types of organisms that cause infection. You will also learn about the most common infections that occur after a transplant. Finally, we will tell you about the drugs that you might need to manage infection.

Organisms that Cause Infection

Bacteria
Most bacteria are harmless or natural helpers to our bodies. We have bacteria that live in and on our bodies that we need to stay healthy - our natural "bacterial flora". For example, bacteria that live in your gut help digest your food. Natural bacteria normally use the resources in our body that harmful bacteria need to become established and cause infection. Bacterial infections occur when harmful bacteria do become established. We also get infections in our bodies when our natural bacteria move to places they should not be. For example, your natural skin bacteria are healthy on the outside of your body but can make you very ill if they become established inside. Bacterial infections are treated with antibiotics. There are many different kinds that are effective against only some bacteria. We will select the best antibiotic for the type of bacterial infection that you have.

Viruses
Viruses are organisms that cause the common cold, influenza (flu) and many childhood illnesses. Most viral infections last only a short time. However, some viruses remain in our bodies forever. For example, the virus that gave you chicken pox as a child remains in the nerve roots of the spine and can cause shingles in adulthood. Herpes simplex, the cold sore virus, resides in the nerves of the face, causing flare-ups of new sores. These "resident viruses" can be problematic after a transplant, especially in the early months when the immunosuppression levels are high. The following provides more detailed information about specific viruses we are concerned about.

Varicella Zoster
This virus causes chicken pox during the initial infection and shingles later in life. If you have not had chicken pox, it is important to notify the transplant team as soon as you know that someone you have been around in the previous two weeks has developed the infection. We will arrange for a shot of antibodies against the virus (VZIG). The antibodies last about six months. After your transplant, do not get vaccinated against chicken pox. The vaccine has live, but very weakened chicken pox viruses. Since you are immunosuppressed, even the weakened chicken pox viruses can cause infection. If you develop shingles, we will treat the illness. Shingles usually starts with a burning pain in your back, followed by a breakout of very painful, fluid-filled blisters. Notify the transplant team immediately of symptoms. Prompt treatment is important.

Herpes Simplex
This virus causes painful sores on the mouth and genitalia. They can spread to other parts of the body if left untreated. The sores usually start with a burning, itchy feeling and development of redness and swelling, followed by a fluid-filled vesicle, then a painful sore. The sores usually take about two to three weeks to heal. Notify the transplant team as soon as you develop the sores so that we can start treatment.

Cytomegalovirus (CMV)
This is a very common virus that causes severe flu-like symptoms. Most people eventually contract the virus, but are unaware that the "flu" was a CMV infection. This virus flares up again in people who are immunosuppressed. Your donor organ can also infect you. The virus may cause muscle pain, weakness, tiredness, respiratory symptoms, diarrhea, nausea, vomiting, hepatitis and a variety of other symptoms. We monitor your blood work and provide preventative medications if your donor was positive for CMV.

Epstein-Barr Virus (EBV)
EBV is commonly referred to as "mono" or "the kissing disease". Like CMV, this virus is contracted eventually by most people. It causes a flu-like illness and most people are not aware they have had it. Some individuals become very ill (infectious mononucleosis) with severe fatigue, sore throat, headache, hepatitis, possibly a rash, painful muscles, fever and aches. You can become infected by your donor organ if you have not already had the virus. If you are negative for EBV, but your donor was positive, we monitor your blood work for the virus and use preventative medications.

Fungus
Fungi also cause infections in our body. "Athlete's foot" is an example of a fungus that causes infection. Yeast infection in the mouth caused by an overgrowth of this naturally occurring fungus sometimes occurs after a transplant. It is commonly called "thrush". Symptoms include a sore mouth and white spots on the insides of your cheeks and on your tongue. You should examine your mouth daily before you brush your teeth. Once home, if you develop symptoms, we will treat the infection. In addition, women will be at an increased risk of vaginal yeast infections and are asked to alert the doctors if this becomes a problem. Do not treat yeast infections yourself with over-the-counter medications due to the negative interaction with the immunosuppressant medications.

Parasites
We have parasites that live in our lungs called Pneumocystis carinii. Given the opportunity, these parasites may cause pneumonia (PCP). For the first six months after your transplant when immunosuppression levels are highest, we will give you medication to prevent the development of pneumonia from this organism.

You may be worried about these organisms and the risk of infection. Remember that common sense is the best approach to caring for yourself. Report any symptoms of infection to the transplant team, follow the infection control suggestions, and relax. Even though you are immunosuppressed, your body can still fight and control infection, especially with a little help from you and your transplant team.

Medications for Preventing and Treating Infection

Co-trimoxazole (Septra®, Bactrim®) Co-trimoxazole is part of the family of medications commonly called "sulfa drugs". It is used to prevent pneumonia from Pneumocystis carinii. You will take the medication for six months after your transplant.

How to take
Taken once daily at the time you prefer.

Side Effects

Pentamidine® — This medication is used as an alternative to co-trimoxazole when it is not suitable (example: allergy). It is used to prevent pneumonia from Pneumocystis carinii.

How to take
Pentamidine® is given by inhalation once a month for six months after your transplant. You will go to the Respiratory Department where a respiratory technician will administer the drug. It is important to keep your appointments for the medication inhalation, as long breaks between doses place you at risk for pneumonia.

Side effects

Ganciclovir (Cytovene®) — This medication is taken by mouth and is used to prevent CMV and EBV infections from your donor organ. In the event you develop infection, larger doses given intravenously will be used to control the infection. You may not require this medication depending on whether or not you or your donor have been previously exposed to these viruses, and the type of immunosuppressant medication you are taking.

How to take
When taken orally, you will take three doses daily: morning, afternoon and evening. You will be on the medication for twelve weeks. If you develop an infection, the oral medication will be stopped and you will be placed on intravenous ganciclovir for fourteen days. The medication is given twice per day, about twelve hours apart.

Side effects

Your Post Transplant Schedule

Blood testing
Every Monday, Wednesday and Friday you will have blood drawn before 8:00 am. For these tests you must be fasting. Do not administer your morning insulin until after the tests have been completed. In addition, do not take your tacrolimus or sirolimus until after your blood work is done.

The frequency of blood testing will decrease over time as your islet tissue begins to work and your drug levels are stabilized. Eventually, you can have your bloodwork done in a lab closer to your home.

For the first blood work of every month, you will have your lipids tested. You will not be able to eat or drink anything other than water for twelve hours before the test. No alcohol for thirty-six hours before the blood test and no caffeine for 12 hours before the test.

Keep track of your daily blood sugars and bring your records to the appointments.

Clinic appointments
You will meet a physician at the Transplant Follow-up Clinic every week. You will be told what changes to make to your medication and how often you have to come for blood work and appointments.

Medication
Always keep a two-week supply of your medication on hand. Tacrolimus and sirolimus can only be obtained at the University of Alberta Hospital Outpatient Pharmacy and Foothills Hospital Pharmacy or at major transplant centres across Canada. If you live outside of Edmonton special arrangements must be made for you to obtain the drug in your area. These arrangements must be made before you leave Edmonton.

Glucose monitoring
Initially, you must monitor your blood glucose levels seven times daily. The frequency will be decreased over time as your glucose levels stabilize. We will obtain the values when your glucometer is downloaded. You are also required to keep written records of your blood sugars and daily insulin use that you will need to bring to each clinic.

Rejection
We will know you are rejecting your new islet tissue when the islets no longer produce insulin. By the time this happens it will probably be too late to treat the rejection medically. It is therefore very important to prevent rejection by maintaining adequate immunosuppression and staying healthy.

Infection
The drugs you are on to stop rejection suppress your immune system. This means that you must take care to prevent or get early treatment for infections. If you have any symptoms of infection such as fever, vomiting, diarrhea or pain, please see your doctor immediately and notify your transplant team.

Additional tests
There are a variety of other tests that will be completed throughout the next five years after your transplant. We will work with you to schedule the appointments as conveniently as we can. Here is an example of a schedule:

An example of follow-up studies and time required

Here is an example of the post transplant yearly schedule:

ADDITIONAL TESTS / APPOINTMENTS: Please book these yourself.

Fundal Photography, Ophthalmologist (Eye Doctor), Family Physician, Dentist, E.C.G. (Electrocardiogram).

For more information contact the Clinical Islet Transplant Program:

Clinical Islet Transplant Program
2000 College Plaza
8215-112th Street Edmonton, Alberta, Canada T6G 2C8
780-407-1501(phone)
780-407-3850(fax)
Email: isletprogram@islet.ca