Stem Cell Transplant Side Effects
Problems soon after transplant
Many of the problems that can happen shortly after the transplant come from having the bone marrow wiped out by medicines or radiation just before the transplant. Others may be side effects of the conditioning treatments themselves.
This is not a complete list and you should tell your doctor or transplant team 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.
Your transplant team can help you cope with side effects. Some can be prevented, and most can be treated to help you feel better.
Mouth and throat pain
Mucositis (inflammation or sores in the mouth) is a short-term side effect that can happen with chemo and radiation. It usually gets better within a few weeks after treatment, but it can make it very painful to eat and drink.
Good nutrition is important for people with cancer. If mouth pain or sores make it hard to eat or swallow, your transplant team will help you develop a plan to manage your symptoms. See Nutrition for the Person With Cancer for more on this.
Nausea and vomiting
Because chemotherapy drugs can cause severe nausea and vomiting, doctors often give anti-nausea medicines at the same time as chemo to try and prevent it. As much as possible, the goal is to prevent nausea and vomiting, because it’s easier to prevent it than it is to stop it once it starts. Preventive treatment should start before the chemo is given and should continue for as long as the chemo is likely to cause vomiting, which can be up to 7 to 10 days after the last dose.
No one drug can prevent or control chemo-related nausea and vomiting 100% of the time. In many cases, two or more medicines are used. You’ll need to tell your transplant team how well the medicines are controlling your nausea and vomiting. If they aren’t working, they will need to be changed.
During about the first 6 weeks after transplant, until the new stem cells start making white blood cells (engraftment), you can easily get serious infections. Bacterial infections are most common during this time, but viral infections that were controlled by your immune system can become active again. Fungal infections can also be an issue. And even infections that cause only mild symptoms in people with normal immune systems can be quite dangerous for you.
You may be given antibiotics to try to prevent infections until your blood counts reach a certain level. For instance, pneumocystis pneumonia (often called PCP) is a common infection that’s easy to catch. Even though the germ doesn’t harm people with normal immune systems, for others it can cause fever, cough, and serious breathing problems. Antibiotics are often used to keep transplant patients from getting this.
Your doctor may check you before the 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 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, see below).
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’re 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.
Your transplant team will tell you and your family in detail about the precautions you need to follow. 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, contact your doctor right away. Tests will be done to look for the cause of the infection (chest x-rays, urine tests, and blood cultures) and antibiotics will be started.
Bleeding and transfusions
After transplant, you’re 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 a certain level, a platelet transfusion may be needed. You’ll need to follow precautions until your platelet counts stay at safe levels.
It also takes time for your bone marrow to start 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 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 if you have graft-versus-host disease (see next section).
You should report any shortness of breath or changes in your breathing to your doctor or transplant team right away. There are many other types of lung and breathing problems that also need to be handled quickly.
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 could have one, both, or neither type of GVHD.
Acute GVHD can happen 10 to 90 days after a transplant, though the average time is around 25 days.
About one-third to one-half of allogeneic transplant recipients will develop 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:
- 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 can be treated. 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, certain 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. Still, mild GVHD will almost always happen in allogeneic transplant patients. Other drugs in different combinations are being tested for GVHD prevention.
The risk of acute GVHD can also be lowered by removing a certain kind of 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 let the donor T-cells destroy any cancer cells left. Preventing and managing GVHD are major priorities for research.
Chronic GVHD can start anywhere from about 90 to 600 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
- 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 painful sores in the mouth
- Burning sensations when eating acidic foods
- Bacterial infections
- Blockages in the smaller 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. Most patients with chronic GVHS can stop the immunosuppressive drugs after their symptoms improve.
Hepatic veno-occlusive disease (VOD)
Hepatic veno-occlusive disease (VOD) is a serious problem in which tiny veins and other blood vessels inside the liver become blocked. It’s not common, and 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 about 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 (this is where the liver is), and quick weight gain (mostly from fluid that bloats 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 prevent and treat this problem are being tested.
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. Still, it’s not very common.
Graft failure can lead to serious bleeding and/or infection. It’s suspected in patients whose counts do not start going 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 rarely fail, but if they do it can result in death.
Transplant problems that may show up later
The type of problems that can happen after a transplant depend on many factors, such as the type of transplant done, the conditioning treatment used, the patient’s overall health, the patient’s age when the transplant was done, the length and degree of immune system suppression, and whether chronic graft-versus-host-disease (GVHD) is present and how bad it is. The problems can be caused by the conditioning treatment (the pre-transplant chemotherapy and radiation therapy), especially total body irradiation, or by other drugs used during transplant (such as the drugs that may be needed to suppress the immune system after transplant). Possible long-term risks of transplant include:
- Organ damage
- Relapse (the cancer comes back)
- Secondary (new) cancers
- Abnormal growth of lymph tissues
- Infertility (the inability to produce children)
- Hormone changes, such as changes in the thyroid or pituitary gland
- Cataracts (clouding of the lens of the eye, which causes vision loss)
The medicines used in transplants can harm the body’s organs, such as the heart, lungs, kidneys, liver, bones/joints, and nervous system. You may need careful follow-up with close monitoring and treatment of the long-term organ problems that the transplant can cause. Some of these, like infertility, should be discussed before the transplant, so you can prepare for them.
It’s important to find and quickly treat any long-term problems. Tell your doctor right away if you notice any changes or problems. Physical exams by your doctor, blood work, imaging tests, lung/breathing studies, and other tests will help look for and keep tabs on organ problems.
As transplant methods have improved, more people are living longer and doctors are learning more about the long-term results of stem cell transplant. Researchers continue to look for better ways to care for these survivors to give them the best possible quality of life.
The goal of a stem cell transplant in cancer is to prolong life and even cure the cancer. But in some cases, the cancer comes back (relapses). Relapse can happen a few months to a few years after transplant. It happens much more rarely 5 or more years after transplant.
After relapse, treatment options are often quite limited. A lot depends on your overall health at that point, and whether the type of cancer you have responds well to drug treatment. Treatment for those who are otherwise healthy and strong may include chemotherapy or targeted therapy. Some patients who have had allogeneic transplants may be helped by getting white blood cells from the same donor (this is called donor lymphocyte infusion) to boost the graft-versus-cancer effect. Sometimes a second transplant is possible. But most of these treatments pose serious risks even to healthier patients, so those who are frail, older, or have chronic health problems are often unable to get them.
Other options may include palliative (comfort) care, or a clinical trial of an investigational treatment. It’s important to know what the expected outcome of any further treatment might be, so talk with your doctor about the purpose of the treatment. Be sure you understand the pros and cons before you decide.
Secondary cancers (new cancers caused by treatment)
Along with the possibility of the original cancer coming back (relapse) after it was treated with a stem cell transplant, there is also a chance of having a second cancer after transplant. Studies have shown that people who have had allogeneic transplants have a higher risk of second cancer than people who got a different type of stem cell transplant.
Cancers that happen a few months after transplant are mainly lymphomas, especially the B-cell types. These seem to be caused by a common virus known as Epstein-Barr virus, or EBV. The immune system can normally keep the virus under control, but EBV can cause cancer — especially when the immune system is being suppressed with drugs, as it is after allogeneic transplant.
Acute leukemia is a type of cancer that can develop a few years after stem cell transplant. Another disorder of the bone marrow called myelodysplasia or myelodysplastic syndrome, in which the bone marrow makes defective blood cells, can also happen a few years after transplant. Myelodysplasia is generally a mild form of cancer, but it can become more aggressive in some people.
Secondary cancers that happen many years later may include solid tumor cancers, often of the skin, mouth, brain, liver, cervix, thyroid, breast, and bone.
Risk factors for developing a second cancer are being studied and may include:
- Radiation (such as total body irradiation) and high-dose chemo as part of the conditioning treatment
- Previous chemo or radiation treatment that was not part of the transplant process
- Immune system problems (such as graft-versus-host disease, HLA-mismatched allogeneic transplant, and immunosuppressant therapy)
- Being older than age 40 at the time of transplant
- Infection with viruses such as Epstein-Barr (EBV), cytomegalovirus (CMV), hepatitis B (HBV), or hepatitis C (HCV)
Some second cancers can show up a few months or a few years after transplant. But second cancers can take many years to develop, so the best studies are in those who have lived a long time after treatment.
Successfully treating a first cancer gives a second cancer time (and the chance) to develop. No matter what type of cancer is treated, and even without the high doses used for transplant, treatments like radiation and chemo can lead to a second cancer in the future.
Post-transplant lymphoproliferative disorder
Post-transplant lymphoproliferative disorder (PTLD) is an out-of-control growth of lymph cells, actually a type of lymphoma, that can develop after an allogeneic stem cell transplant. It’s linked to a malfunction of T-cells (a type of white blood cell that is part of the immune system) and the presence of Epstein-Barr virus (EBV). T-cells normally help rid the body of cells that contain viruses. When the T-cells aren’t working well, EBV-infected B-lymphocytes (a type of white blood cell) can grow and multiply. Most people are infected with EBV at some time during their lives, but the infection is controlled by a healthy immune system. The conditioning treatment given before transplant weakens the immune system, allowing the EBV infection to get out of control, which can lead to a PTLD.
Still, PTLD after allogeneic stem cell transplant is fairly rare. It most often happens within 1 to 6 months after allogeneic stem cell transplant, when the immune system is still very weak.
PTLD is life-threatening. It may show up as lymph node swelling, fever, and chills. There’s no one standard treatment, but it’s often treated by cutting back on immunosuppressant drugs to let the patient’s immune system fight back. Other treatments include white blood cell (lymphocyte) transfusions to boost the immune response, using drugs like rituximab to kill the B cells, and giving anti-viral drugs to treat the EBV.
Even though PTLD doesn’t often happen after transplant, it’s more likely to occur with less well-matched donors and when strong suppression of the immune system is needed. Studies are being done to identify risk factors for PTLD and look for ways to prevent it in transplant patients who are at risk.
Stem cell transplant and having children
Most people who have stem cell transplants become infertile (unable to have children). This is not caused by the cells that are transplanted, but rather by the high doses of chemo and/or radiation therapy used. These treatments affect both normal and abnormal cells, and often damage reproductive organs.
If having children is important to you, or if you think it might be important in the future, talk to your doctor before treatment about ways to protect your fertility. Your doctor may be able to tell you if a particular treatment will be likely to cause infertility.
After chemo or radiation, women may find their menstrual periods become irregular or stop completely. This doesn’t always mean they cannot get pregnant, so birth control should be used before and after a transplant. The drugs used in transplants can harm a growing fetus.
The drugs used during transplant can also damage sperm, so men should use birth control to avoid starting a pregnancy during and for some time after the transplant process. Transplants may cause temporary or permanent infertility for men as well. Men might consider storing their sperm before having a transplant. This process can take several days. Fertility returns in some men, but the timing is unpredictable.
For more information on having children after being treated for cancer or sexual problems related to cancer treatment, see Fertility and Sexual Side Effects.
Bhatia S, Bhatia R. Transplantation-Related Malignancies. In: DeVita VT, Lawrence TS, Rosenberg SA, eds. Cancer: Principles and Practice of Oncology, 9th ed. Philadelphia, Pa: Wolters Kluwer/Lippincott Williams & Wilkins; 2011: 2113-2122.
Childs RW. Allogeneic stem cell transplantation. In: DeVita VT, Lawrence TS, Rosenberg SA, eds. Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Wolters Kluwer/Lippincott Williams & Wilkins; 2011:2244-2261.
Gallagher G, Forrest DL. Second Solid Cancers After Allogeneic Hematopoietic Stem Cell Transplantation. Cancer. 2007;109:84-92.
Harper JL, Corbacioglu S. Veno-occlusive Hepatic Disease, 6/22/10. Accessed at http://emedicine.medscape.com/article/989167-overview on August 30, 2013.
Harrison N, Mitterbauer M, Tobudic S, et al. Incidence and characteristics of invasive fungal diseases in allogeneic hematopoietic stem cell transplant recipients: a retrospective cohort study. BMC Infect Dis. 2015;15:584.
Solano C, Giménez E, Piñana JL, et al. Preemptive antiviral therapy for CMV infection in allogeneic stem cell transplant recipients guided by the viral doubling time in the blood. Bone Marrow Transplant. 2015 Dec 7.
Sundin M, Le Blanc K, Ringden O, et.al. The role of HLA mismatch, splenectomy and recipient Epstein-Barr virus seronegativity as risk factors in post-transplant lymphoproliferative disorder following allogeneic hematopoietic stem cell transplantation. Haematologica/The Hematology Journal. 2006;91:1059-1067.
Vargo MM, Smith RG, Stubblefield MD. Rehabilitation of the Cancer Patient. In: DeVita VT, Lawrence TS, Rosenberg SA, eds. Cancer: Principles and Practice of Oncology. 8th ed. Philadelphia, Pa: Wolters Kluwer/Lippincott Williams & Wilkins; 2008:2857-2883.
Williams KM, Chien JW, Gladwin MT, Pavletic SZ. Bronchiolitis obliterans after allogeneic hematopoietic stem cell transplantation. JAMA. 2009;302(3):306-314.
Zamkoff KW, Bergman S, Beaty MW, et. al. Fatal EBV-related post-transplant lymphoproliferative disorder (LPD) after matched related donor nonmyeloablative peripheral blood progenitor cell transplant. Bone Marrow Transplantation. 2003;31:219-222.
Last Medical Review: May 11, 2016 Last Revised: May 11, 2016