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Side effects of stem cell transplant

Infection

Bleeding

Anemia

Graft-versus-host disease

Veno-occlusive disease

Digestive system problems

Skin and hair problems

Pain

Inflammation of the parotid gland

Engraftment syndrome

Capillary leak syndrome

Lung problems

Kidney problems

Nerve and muscle problems

Graft failure

Graft (stem cell) rejection

Heart problems

Eye problems

Thyroid problems

Developmental problems

Bladder problems

Central nervous system problems

Fertility problems

Second cancers

 

Side effects can occur with any type of treatment, but not everyone has them or experiences them in the same way. Side effects of a stem cell transplant will depend mainly on:

  • the type of chemotherapy drug(s) used
  • whether radiation therapy was given before the transplant
  • the type of transplant
    • autologous (the person’s own stem cells are used)
    • allogeneic or syngeneic (stem cells come from a donor)
  • the person’s overall health

 

A stem cell transplant is a very complex procedure. The side effects can be very serious and may be life-threatening. The chance that serious problems will develop depends on the recipient’s age and general physical condition before the transplant.

 

Side effects can happen at any time during, immediately after or days to months after treatment. Short-term side effects (sometimes called acute site effects) generally occur during the first 100 days after a stem cell transplant. Long-term side effects (also called chronic side effects) generally appear 100 days or more after the transplant. Some side effects of stem cell transplant can last a long time or be permanent. Late side effects can occur months or years after treatment.

 

It is important to report side effects to the healthcare team. Doctors may grade (measure) how severe certain side effects are. The healthcare team will monitor people receiving transplants very closely, and will take measures to prevent and quickly deal with side effects.

 

All types of stem cell transplants share some of the same side effects. Many common side effects, such as nausea, vomiting, fatigue and temporary hair loss, are due to chemotherapy or radiation therapy. Some other side effects are unique to high-dose therapy and stem cell transplant. The following are the most common side effects that people tend to experience with stem cell transplant. Some people may experience all, some or none of these side effects. Others may experience different side effects.

Infection

Infection is one of the most common early side effects of a stem cell transplant. It can also be a very serious problem. Infection occurs after stem cell transplant because the white blood cell count is very low and the immune system is very weak. This risk of infection is highest until the bone marrow starts to produce white blood cells (engraftment), which takes 2–4 weeks.

 

The most common sites of infection include:

 

Bacterial infections are the most common. Viral or fungal infections can also occur. Recipients of allogeneic transplants have the highest risk of infection because their immune system may be suppressed to prevent graft-versus-host disease (GVHD). The healthcare team carefully monitors transplant recipients for signs of infection. Fever is often the first sign.

 

Special precautions are taken until the white blood cell count is back to normal and the body can fight infections. Different transplant units may have different precautions and guidelines. Precautions include:

  • The recipient may be restricted to a room of their own (protective isolation) with special ventilation.
  • Visitors may be limited. They have to wash their hands before visiting the recipient. Anyone who feels unwell and children exposed to an infectious disease (such as chicken pox or measles) should not visit.
  • The recipient often has to follow dietary restrictions and food safety guidelines.

 

Even if there is no sign of infection, antibiotics or antiviral drugs are often given until white blood cell counts start to rise. Colony-stimulating factors (CSFs), such as filgrastim (Neupogen) or pegfilgrastim (Neulasta), may be given following a stem cell transplant to help lower the risk of infection and speed up engraftment.

 

Infection can also occur long after a stem cell transplant. Late infections commonly occur in the skin, upper respiratory tract and lungs. The risk of late infection is related to:

  • how quickly the recipient’s immune system recovers
  • GVHD, which is a major risk factor for infection
  • whether or not the recipient needs to take immune-suppressing drugs

 

The recipient is taught what signs to watch for and what to do if they occur. Medicines may be needed when infections do occur. It takes the immune system 6–12 months to recover after a transplant. Recipients should talk to their doctor about being re-vaccinated 1–2 years after the transplant. Most people need to be immunized with vaccines that are commonly given in childhood (such as polio and measles vaccines) to help restore the immune system.

 

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Bleeding

Bleeding is another common side effect of stem cell transplant. It occurs because conditioning or intensive therapies can cause a low platelet count, which reduces the blood’s clotting ability. Serious bleeding problems (hemorrhage) can occur. The red blood cell count can also be lowered, which can lead to anemia.

 

Blood tests are done daily to check the number of the different types of blood cells. The healthcare team monitors recipients for signs of bleeding, such as nosebleeds, easy bruising and bleeding gums.

 

The healthcare team takes measures to lower the chance of bleeding. Platelet transfusions may be needed until transplanted stem cells start to work, especially during the first month after the transplant.

 

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Anemia

Conditioning or intensive therapies can cause a low red blood cell count and a lower concentration of hemoglobin, which is called anemia. Anemia can cause fatigue, paleness and malaise.

 

Colony-stimulating factors, such as epoetin alfa (Eprex, erythropoietin) or darbepoetin (Aranesp), may be given to help increase red blood cell counts. Red blood cell transfusions may also be needed if blood cell counts drop too low.

 

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Graft-versus-host disease

Acute graft-versus-host disease (GVHD) occurs when the donor’s transplanted stem cells (graft) see the recipient’s (host) cells as different and attack them. Chronic GVHD is the most common late problem that can occur after a stem cell transplant. Many other late problems are related to GVHD.

 

Immune-suppressing drugs are used to prevent and treat GVHD. The recipient may have to take these drugs for months or years after an allogeneic transplant. The donor’s T cells may be removed (T-cell depletion) from the stem cells before the transplant to help reduce the chance of GVHD.

 

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Veno-occlusive disease

Veno-occlusive disease (VOD) can develop in the first few weeks after stem cell transplant. Small blood vessels that lead to the liver can become blocked, which can lead to liver damage. VOD is more common after an allogeneic transplant. There is no definite way to prevent or treat VOD, but most people can manage symptoms with medicines, lowering salt intake and monitoring their fluids.

 

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Digestive system problems

Digestive system problems frequently occur shortly after a stem cell transplant. Digestive system problems include:

  • inflammation and sores in the mouth (stomatitis or oral mucositis)
  • nausea
  • vomiting
  • loss of appetite
  • weight loss
  • diarrhea

 

Digestive system problems occur because tissues in the mouth, stomach and intestines are affected by different aspects of the stem cell transplant process. Digestive problems can be caused by:

  • the conditioning therapy
  • infection
  • GVHD

 

The recipient is encouraged to eat small meals and snacks. Nutritional or food supplements may be used. For severe eating problems, a special fluid (total parenteral nutrition, or TPN) may be given through the central venous catheter to provide nutrition. Special mouthwashes or lozenges and pain medicines are used for a sore mouth. Good mouth care is needed. Medicines are used to control diarrhea, nausea and vomiting.

 

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Skin and hair problems

Skin rash is common when certain chemotherapy drugs (such as busulfan) and total body irradiation (TBI) are used for conditioning or intensive therapy. Temporary hair loss (alopecia) can also occur after conditioning.

 

The healthcare team may encourage recipients to have daily baths or showers to remove bacteria from the skin and lower the chances of skin rash. Scarves, hats and wigs can be worn until hair grows back, which usually happens within 3–6 months after the transplant. Hair loss is rarely permanent.

 

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Pain

Pain occurs when tissues or nerves are inflamed. Pain can be caused by:

  • the conditioning or intensive therapy
  • infection
  • veno-occlusive disease (VOD)
  • medicines
  • mouth sores
  • skins sores or rashes
  • intestinal problems

 

Pain medicines are used to relieve the pain. Other therapies (such as relaxation or visualization) may also be used to help relieve pain.

 

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Inflammation of the parotid gland

The parotid gland produces saliva. It is near the ear. It can become inflamed soon after the first or second treatment of total body irradiation (TBI). This causes pain and swelling on both sides of the jaw. It looks like the swelling that happens with mumps. It can be relieved by warm compresses and pain medicines. The inflammation usually goes away within several days.

 

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Engraftment syndrome

Engraftment syndrome includes fever (not due to infection), skin rash, diarrhea, weight gain and fluid in the lungs (pulmonary edema). It is thought to be due to the immune system releasing chemicals (cytokines) in response to the high-dose conditioning therapy. Engraftment syndrome may occur before the bone marrow starts to work on its own. Steroid medicines may be used to treat engraftment syndrome.

 

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Capillary leak syndrome

Conditioning or intensive therapy can damage different tissues in the body, including blood vessels. If tiny blood vessels (capillaries) are damaged, fluids can leak out of the capillaries into the body and upset the fluid balance in the body. This can result in fluid retention, weight gain, buildup of fluid in the abdomen (ascites), cough, shortness of breath and buildup of fluid in the lungs (pulmonary edema). Capillary syndrome usually occurs about 1–2 weeks after stem cell transplant. Medicines and other treatments, such as oxygen therapy, are given to treat this side effect.

 

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Lung problems

Lung problems can develop because of the conditioning or intensive therapy or infection. They can also occur if the person is given too much fluid after a stem cell transplant. Damage to the lungs can result in:

  • lung congestion (pulmonary edema)
  • pneumonia (occurs after exposure to bacteria, viruses or fungi)
  • interstitial pneumonia
    • Interstitial pneumonia is a type of pneumonia that commonly occurs within the first 100 days of a stem cell transplant. It is caused by a tissue reaction. Late interstitial pneumonia is often associated with GVHD.
  • restrictive disease or obstructive lung diseases
    • The cause of restrictive or obstructive lung diseases is not fully known. These diseases affect lung function and can be a serious long-term problem.

 

Lung problems are common in people with GVHD. The healthcare team monitors the recipient for lung problems. They may take chest x-rays and check lung function. Medicines may be used to prevent infection right after a stem cell transplant. Medicines are also used to treat certain lung conditions.

 

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Kidney problems

Kidney (renal) problems can occur when the kidneys are damaged. Kidneys can be damaged by:

  • chemotherapy drugs used in conditioning or intensive therapy
  • antibiotic therapy
  • cyclosporine (Neoral) – a drug used to suppress the immune system

 

Sometimes kidney problems become so severe that they can lead to kidney failure, which is a long-term problem. The healthcare team monitors the amount of fluids the recipient takes in and puts out. They also assess kidney function. Measures are taken to reduce damage to the kidneys as much as possible.

 

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Nerve and muscle problems

Nerve and muscle problems can occur because of the conditioning or intensive therapy or infection. Immune-suppressing drugs (such as cyclosporine or steroids) can also cause nerve and muscle problems.

 

Nerve and muscle problems may occur about 3 weeks after stem cell transplant. They may cause:

  • sleepiness (somnolence)
  • confusion
  • disorientation
  • numbness, tingling or burning in the hands or feet (peripheral neuropathy)
  • muscle weakness

 

The healthcare team monitors the recipient for any neurological signs so that they can be treated quickly.

 

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Graft failure

Graft failure is a rare side effect of stem cell transplant. It occurs when donated stem cells (graft) don’t start to produce new blood cells or they start to function but then suddenly stop. It may be necessary to give more stem cells from the same donor.

 

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Graft (stem cell) rejection

Graft or stem cell rejection occurs if the recipient’s body rejects the transplanted stem cells. This is more common in allogeneic transplants, especially when the donor is unrelated or less well matched to the recipient.

 

Graft rejection is a serious problem. Sometimes it can be treated with growth factors. In some cases, a second transplant can be done.

 

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Heart problems

Heart (cardiac) problems are not common, but they can occur after stem cell transplant. Certain chemotherapy drugs, such as cyclophosphamide (Cytoxan, Procytox), can cause the heart to function less efficiently or cause inflammation of the tissue surrounding the heart (pericarditis).

 

A multigated acquisition (MUGA) scan checks how well the heart is working and assesses any damage to the heart muscle. It may be done before high-dose therapy is given. Chemotherapy drugs that are less damaging to the heart may be used during conditioning. Medicines can be used to treat heart problems that develop after stem cell transplant.

 

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Eye problems

Eye problems, mainly cataracts, can occur in people who received total body irradiation (TBI) as conditioning or intensive therapy. These problems usually develop 1 year after stem cell transplant, but they can also happen several years later. Chemotherapy and steroids may also increase the chance of developing cataracts. The chance of developing cataracts also increases with age. A cataract clouds the lens of the eye and can cause vision loss. Stem cell transplant recipients are encouraged to have regular eye examinations.

 

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Thyroid problems

The risk of developing thyroid problems is quite high when total body irradiation (TBI) is used for conditioning or intensive therapy before a stem cell transplant. Hypothyroidism is the most common thyroid problem. This is a condition in which the thyroid does not make enough thyroid hormone. Symptoms of hypothyroidism include fatigue, weight gain, hair loss, brittle nails, dry skin and feeling cold.

  • In adults, thyroid function may be checked each year. Thyroid hormone replacement therapy may be needed if the thyroid is not working properly (is underactive).
  • In children, thyroid hormone deficiency will lead to lowered metabolism and slowed physical and mental development.
    • The child’s thyroid function is checked often. Medicine (thyroid hormone replacement) may be needed daily to regulate the thyroid gland.
    • Hypothyroidism in children usually develops 3–4 years after treatment and can become a long-term problem.

 

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Developmental problems

In children, developmental and growth delays are long-term effects of total body irradiation (TBI). This occurs because the hypothalamus in the brain controls the release of growth hormones. The hypothalamus is affected by radiation therapy to the head, which leads to lower levels of growth hormones. Low levels of growth hormone will result in shortened stature, shortened limbs and lessened overall physical development. Steroid medicines and GVHD can also affect growth. Treatment with growth hormones may be needed.

 

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Bladder problems

Bladder problems can occur when chemotherapy drugs used during conditioning or intensive therapy scar the bladder wall. This can lead to frequent urination or blood in the urine. Drugs that suppress the immune system can cause recurring bladder infections. Medicines or surgery may be needed to treat bladder problems.

 

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Central nervous system problems

The central nervous system (CNS) is made up of the brain and spinal cord. Several aspects of the stem cell transplant process can affect brain tissue, including:

  • chemotherapy used in conditioning or intensive therapy
  • radiation therapy to the brain
  • chronic GVHD
  • infection
  • cancer that comes back (recurs)

 

CNS problems can include damage to the brain (leukoencephalopathy) and problems with mental (cognitive) functioning. This can result in poor concentration, difficulty with memory and difficulty learning new tasks. CNS problems can develop months or years after stem cell transplant.

 

Report changes in mental functioning to the doctor or healthcare team. They may refer the person for neurological assessment. Many people deal with cognitive changes by changing the way they manage information.

 

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Fertility problems

Infertility (inability to conceive a child) can occur because of chemotherapy or radiation therapy used for conditioning or intensive therapy. Not all people having stem cell transplants will become infertile. If the person received extensive treatment for their cancer before a transplant, they may already be infertile.

  • After high-dose chemotherapy or radiation therapy, a woman’s menstrual periods may become irregular or stop. Premature menopause can occur. Measures can be used to help cope with menopausal symptoms, such as hot flashes.
  • Women may choose to freeze and store fertilized eggs (embryos) to be implanted after transplant and recovery.
  • Men may choose to freeze and store their sperm for future use.

 

In children, sexual development and fertility problems may mean that sexual development starts at a later date or doesn’t progress at a normal rate. This can happen when the hypothalamus, which produces hormones that regulate sexual development, is affected by total body irradiation (TBI).

  • At any age, TBI can cause the reproductive organs (also called gonads) to stop working in boys and girls. This is called primary gonad failure. Gonad failure and infertility can be permanent. Hormone replacement therapy may be needed.
  • Some chemotherapy drugs can affect the function of the reproductive organs.
  • Girls who were treated before puberty may have fewer problems with ovarian function and regular menstruation than girls treated after puberty.
  • Boys who were treated before puberty may have fewer problems with fertility than boys treated during or after puberty. A boy may become sterile, have an absence of sperm in the semen (azoospermia) and experience premature ejaculation.

 

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Second cancers

Other cancers can develop because of the amount of chemotherapy and radiation therapy given during conditioning or intensive therapy. These can include:

  • acute leukemia
  • solid tumours (melanoma, head and neck cancers, brain cancer, liver cancer, bone cancer and sarcoma)
  • myelodysplastic syndrome (MDS)
  • lymphoma (particularly B-cell lymphoma)

 

These second cancers can develop several years after a stem cell transplant. Doctors will check  for  cancer that has come back (recurs) or any new cancers during follow-up.

 

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References

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