After-transplant problems that may show up later

The type of problems that can happen after 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 at the time of transplant, the length and degree of immune system suppression, and whether chronic GVHD is present and how bad it is. The problems can be caused by the conditioning treatment (the pre-transplant chemo 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). Potential long-term risks of transplant include:

• Organ damage (to the liver, kidneys, lungs, heart and/or bones and joints)
• 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)

Organ problems

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 early in the transplant process, so you can prepare for them.

It’s important to find and quickly treat any long-term problems. Physical exams by your doctor, blood work, imaging studies, and telling your doctor about any changes or problems you’ve noticed will help with this. Your breathing may also be tested regularly to see if your lungs are showing signs of GVHD.

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.

Cancer relapse

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. 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 (new) cancers

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. The general risk of getting another cancer after a transplant is estimated to be 4 to 11 times that of people who have not had transplants.

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 transplants. Another disorder of the bone marrow called myelodysplasia (my-uh-lo-dis-PLAY-zhuh) or myelodysplastic syndrome (my-uh-lo-dis-PLAS tick), in which the bone marrow makes defective blood cells, can also happen a few years after transplant. Myelodysplasia is not really a cancer, but it can develop into cancer in some people. For more, see our document called Myelodysplastic Syndromes.

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. For more information on this, please see our document called Second Cancers Caused by Cancer Treatment.

Post-transplant lymphoproliferative disorder

Post-transplant lymphoproliferative (lim-fo-pruh-LIH-fer-uh-tiv) disorder (PTLD) is an out-of-control growth of lymph cells that can be seen 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 rare. It most often happens in recipients of T-cell-depleted stem cells. It can happen in recipients of stem cells that came from a mismatched or unrelated donor. It also happens in people who need anti-thymocyte globulin (ATG) or anti-CD3 monoclonal antibody for treatment of acute graft-versus-host disease (GVHD). Recipients who got stem cells from older donors and recipients who had severe immune problems before transplant may also have a higher risk of developing a PTLD.

PTLDs most often happen within 1 to 6 months after 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 is 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 Rituxan to kill the B cells, and giving anti-viral drugs to treat the EBV.

Even though PTLD doesn’t happen a lot after transplant, it’s likely to happen more as the use of less-matched donors and the need for strong suppression of the immune system goes up. Studies are being done to identify risk factors for PTLD and look for ways to watch for 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 transplant itself, 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 save 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.

Men might consider storing their sperm before having a transplant. Sperm samples are collected, then frozen and stored in a sperm bank. This process can take several days. The stored sperm can later be thawed and used to fertilize a partner’s egg using artificial insemination.

Other kinds of reproductive techniques, including cryogenic preservation (freezing) of embryos, sperm, and eggs are available for future donation. Adoption is another of the many possibilities for couples who want to have families after transplant.

For more information see our document called Fertility and Cancer: What Are My Options?

Weigh the risks before transplant

Despite the possible long- and short-term problems, stem cell transplant has been used to cure thousands of people with otherwise deadly cancers. Still, the possible risks and complications can threaten life, too; and they must be weighed carefully before transplant. Research today is being done to not only to cure cancer, but also to improve transplant methods and reduce the chance of problems after transplant.