Problems that may come up shortly after transplant

This is a review of some of the more common problems that may happen shortly after transplant. Many of them come from having the bone marrow wiped out by medicines or radiation just before the transplant. Others may result from the specific medicines used for the conditioning phase, or from the radiation. Some of these problems tend to happen less often and be less severe in people who get mini-transplants.

This is not a complete list and you should tell your doctor about any problems you have or changes you notice. Some of these problems can be life-threatening, so it’s important to be able to reach your doctor or transplant team at night, on weekends, and during holidays. Be sure you know how to do this.

Infection

During the first 6 weeks after transplant, until the new bone marrow starts making white blood cells (engraftment), you can easily get serious infections. While your white blood cell counts are low, you are said to be neutropenic. (See “White blood cells” in the section called “What are stem cells and why are they transplanted?” for more information.) Bacterial infections are most common during this time, but viral infections that were controlled by your immune system can become active again. And even infections that cause only mild symptoms in people with normal immune systems can be quite dangerous for you.

As discussed in “Recovery” in the section called “The transplant process,” you may be given antibiotics to try to prevent infections until your blood counts reach a certain level. For instance, pneumocystis pneumonia (PCP) is a common infection that is easy to catch. Even though it doesn’t harm people with normal immune systems, for others it can cause fever, cough, and serious breathing problems. Doctors often give antibiotics to keep patients from getting this.

Your doctor may check you before transplant for signs of certain infections that may become active after transplant, and give you special medicines to keep those germs under control. For example, the virus called CMV (cytomegalovirus) is a common cause of pneumonia in people who have had transplants. It mainly happens to people who were already infected with CMV, or whose donor had the virus. If neither you nor your donor had CMV, the transplant team might follow special precautions to prevent infection while you are in the hospital.

After engraftment, the risk of infection is lower, but it still can happen. It takes 6 months to a year after a transplant for the immune systems of most patients to work as well as they should. It can take even longer for patients with graft-versus-host disease (GVHD).

Because of the increased risk, you will be watched closely for signs of infection, such as fever, cough, shortness of breath, or diarrhea. Your doctor may check your blood often, and extra precautions will be needed to avoid exposure to germs. While in the hospital, everyone who enters your room must wash their hands well. They may also wear gowns, shoe coverings, gloves, and masks.

Since flowers and plants can carry bacteria and fungi, they are not allowed in your room. For the same reason, you may be told not to eat certain fresh fruits and vegetables. All your food must be well cooked and handled very carefully by you and family members. Certain foods may need to be avoided for a while.

You may also be told to avoid contact with soil, feces (stool, both human and animal), aquariums, reptiles, and exotic pets. Your team may tell you to avoid being near disturbed soil, bird droppings, or mold. You will need to wash your hands after touching pets. Your family may need to move the cat’s litter box away from places you eat or spend your time. Some transplant teams recommend cleaning carpets, floors, furniture, and drapes before you go home. Your transplant team will tell you and your family in detail about the precautions you need to follow during this time. There are many viruses, bacteria, and fungi that can cause infection after your transplant.

Despite all these precautions, patients often develop fevers, one of the first signs of infection. If you do get a fever or other signs of infection, tests will be done to look for the cause of the infection (chest x-rays, urine tests, and blood cultures) and IV (intravenous) antibiotics will be started right away. Be sure to ask which symptoms you should call the doctor about at nights and on weekends.

Bleeding and transfusions

After a transplant, you are at risk for bleeding because the conditioning treatment destroys your body’s ability to make platelets. (Platelets are the blood cells that help blood to clot.) While you wait for your transplanted stem cells to start working, your transplant team may have you follow special precautions to avoid injury and bleeding. Platelet counts are low for at least 3 weeks after transplant. In the meantime, you might notice easy bruising and bleeding, such as nosebleeds and bleeding gums. If your platelet count drops below 20,000/mm³ (this is called thrombocytopenia), a platelet transfusion may be needed. You will need to follow precautions until your platelet counts stay at safe levels. (See “Platelets ” in the section called “What are stem cells and why are they transplanted?” for more information.)

It also takes time for your bone marrow to begin making red blood cells, and you might need red blood cell transfusions from time to time as you recover.

Interstitial pneumonitis and other lung problems

Pneumonitis is a type of lung inflammation that’s most common in the first 100 days after a stem cell transplant. But some lung problems can happen much later — even 2 or more years after transplant.

Pneumonia caused by infection happens more often, but pneumonitis may be caused by radiation, graft-versus-host disease, or chemo rather than germs. It’s caused by damage to the areas between the cells of the lungs (called interstitial spaces). Pneumonitis can be severe, especially if total body irradiation was given with chemo as part of the conditioning treatment. Chest x-rays will be taken in the hospital to watch for pneumonitis as well as pneumonia. Some doctors will do breathing tests every few months to try to find lung problems early.

There are many other types of lung and breathing problems that also need to be handled quickly. You should report any shortness of breath or changes in your breathing to your doctor or transplant team right away.

Graft-versus-host disease

Graft-versus-host disease (GVHD) can happen in allogeneic transplants when the immune cells from the donor see the recipient’s body as foreign. (Remember: The recipient’s immune system has mostly been destroyed by conditioning treatment and cannot fight back — the new stem cells make up most of the immune system after transplant.) The donor immune cells may attack certain organs, most often the skin, gastrointestinal (GI) tract, and liver. This can change the way the organs work and increase the chances of infection.

GVHD reactions are very common and can range from barely noticeable to life-threatening. Doctors think of GVHD as acute or chronic. Acute GVHD starts soon after transplant and lasts a short time. Chronic GVHD starts later and lasts a long time. A person may have one, both, or neither type of GVHD.

Acute GVHD

Acute GVHD can happen 10 to 70 days after a transplant, though the average time is around 25 days.

About one-third to one-half of allogeneic transplant recipients develops acute GVHD. It’s less common in younger patients and in those with closer HLA matches between donor and recipient.

The first signs are usually a rash, burning, and redness of the skin on the palms and soles. This can spread over the entire body. Other symptoms include:

• Nausea
• Vomiting
• Stomach cramps
• Diarrhea (watery and sometimes bloody)
• Loss of appetite
• Yellowing of the skin and eyes (jaundice)
• Abdominal (belly) pain
• Weight loss

Most cases are mild, and those who develop it usually have no long-term effects. How well a person does depends on how bad the GVHD is. Some cases of GVHD can lead to death.

Doctors try to prevent acute GVHD by giving drugs, such as steroids, monoclonal antibodies, methotrexate, cyclosporine, and tacrolimus to lessen the immune response. These drugs are given before acute GVHD starts and can help prevent serious GVHD, but mild GVHD will almost always happen in allogeneic transplant patients. New and old drugs in different combinations are being tested for GVHD prevention.

The risk of acute GVHD can also be decreased by removing some of the immune cells (called T-cells) from the donor stem cells before the transplant. But this can also increase the risk of viral infection, leukemia relapse, and graft failure (which is discussed later). Researchers are looking at new ways to remove only certain cells, called alloactivated T-cells, from donor grafts. This would reduce the severity of GVHD and still allow the donor T-cells to destroy any cancer cells left. Preventing and managing GVHD are major priorities for research.

Chronic GVHD

Chronic (ongoing) GVHD can start anywhere from about 70 to 400 days after the stem cell transplant. A rash on the palms of the hands or the soles of the feet is often the earliest sign. The rash can spread and is usually itchy and dry. In severe cases, the skin may blister and peel, like a bad sunburn. A fever may also develop. Other symptoms of chronic GVHD can include:

• Decreased appetite
• Diarrhea
• Abdominal (belly) cramps
• Weight loss
• Yellowing of the skin and eyes (jaundice)
• Enlarged liver
• Bloated abdomen (belly)
• Pain in the upper right part of the abdomen (belly)
• Increased levels of liver enzymes in the blood (seen on blood tests)
• The skin feels tight
• Dry, burning eyes
• Dryness or sores in the mouth
• Burning sensations when eating acidic foods
• Bacterial infections
• Blockages in airways of the lungs

Chronic GVHD is treated with medicines that suppress the immune system, much like those used for acute GVHD. These drugs can increase your risk of infection for as long as you are treated for GVHD (see the “Infection” section).

Hepatic veno-occlusive disease

Hepatic veno-occlusive disease (VOD) is a serious problem in which blood flow inside the liver is blocked. It only happens in people with allogeneic transplants, and mainly in those who got the drugs busulfan or melphalan as part of conditioning.

VOD usually happens within 3 weeks of conditioning. It’s more common in older people who had liver problems before the transplant, and in those with acute GVHD. It starts with yellowing skin and eyes, dark urine, tenderness below the right ribs, and quick weight gain (mostly from bloating in the belly). Sometimes it can result in liver failure and death.

Doctors have found that giving busulfan in the vein (IV) rather than by mouth may reduce the risk of VOD. New ways to treat this problem are being tested.

Graft failure

Grafts fail when the body does not accept the new stem cells (the graft). The stem cells that were given do not go into the bone marrow and multiply like they should. Graft failure is more common when the patient and donor are not well matched and when patients get stem cells that have had the T-cells removed. It can also happen in patients who get a low number of stem cells, such as a single umbilical cord unit.

Graft failure can lead to serious bleeding and/or infection. It’s suspected in patient’s whose counts do not begin to go up within 3 to 4 weeks of a bone marrow or peripheral blood transplant, or within 7 weeks of a cord blood transplant.

It may be treated by a second dose of stem cells, if available. Grafts very rarely fail, but if they do it can result in death.