Stem cell transplantation in the treatment of cancer

There are three main types of treatment for cancer: surgery, medication (chemotherapy and/or hormone therapy) and radiotherapy. You may also have heard of a treatment called bone marrow transplantation, also called blood stem cell transplantation (stem cell transplantation for short) or hematopoietic stem cell transplantation. This type of stem cell transplantation is mainly used to treat various forms of leukemia (or leukaemia).

Stem cell transplantation is not actually a cancer treatment in itself. Instead, the aim is to replace the vitally important blood stem cells that are destroyed during high-dose chemotherapy. This makes it possible to use much higher doses of chemotherapy, and to treat patients who have not responded well to other treatments. Some types of stem cell transplantation can help to fight cancer cells too. This is because donor cells can attack cancer cells that remain after chemotherapy.

Unlike organ transplants, stem cell transplants do not involve surgery. Instead, a liquid containing the stem cells is fed into your blood through a drip, in a similar way to how blood transfusions are done. But this is not a harmless procedure. On the contrary: stem cell transplantation is very demanding, both physically and emotionally, and it can lead to serious, sometimes life-threatening complications. Perhaps you have already had chemotherapy and/or radiotherapy and know how draining and distressing this kind of treatment can be. The time following a stem cell transplant is often unsettling and worrying for patients and their families.

There are different types of stem cell transplantations, so it can be hard to keep track of them all. In this fact sheet we will describe the various types and how they differ. You can also read about possible adverse effects and complications, as well as how people cope with this intensive treatment. You will find a brief overview of the various cancer treatments including stem cell transplantation here.

What are blood stem cells?

Human blood is made up of about half liquid (blood plasma) and half blood cells. Generally speaking, there are three types of blood cells:

• Red blood cells (erythrocytes) transport oxygen and carbon dioxide.
• White blood cells (leukocytes) protect the body from germs.
• Blood platelets (thrombocytes) help blood to clot and wounds to heal.

You can read more about the different types of blood cells and what they do here.

Blood cells do not live long. Depending on the kind of blood cell, they live for anything between several days and several months. Because of this, many billions of blood cells, particularly red blood cells, are replaced every day in the adult human body. The blood stem cells (or simply “stem cells”) are responsible for this. They are in effect the “mother cells” of all blood cells, from which all other blood cells develop. Stem cells are mainly found in bone marrow, and some are found in the blood itself. Bone marrow is a spongy tissue that is found inside certain bones, such as the hip bones.

Stem cells divide and multiply all the time to make sure there are enough blood cells in the body. When a stem cell divides, two new cells arise: one is a new stem cell, and the other goes through several stages of development to finally become a white blood cell, a red blood cell or a blood platelet. The mature blood cell then leaves the bone marrow and enters the bloodstream.

What is blood stem cell transplantation?

There are two reasons why stem cell transplantation is considered as a treatment option. One reason is to replace damaged blood stem cells that no longer work properly. This is the case in, for example, aplastic anaemia – a very rare blood condition where the body does not make enough blood cells. Another reason is to treat certain forms of cancer, such as leukemias. Here, stem cell transplantation is combined with high-dose chemotherapy. This fact sheet is about stem cell transplantation in the treatment of cancer.

Most cancers are treated with surgery, chemotherapy and/or radiotherapy. But sometimes this treatment is not successful. If that is the case, other treatments might be considered, such as stem cell transplantation. Strictly speaking, this is actually high-dose chemotherapy followed by a blood stem cell transplantation. The medically correct term for this is “hematopoietic stem cell transplantation” (HSCT). “Hematopoietic” means “blood-forming”.

High-dose chemotherapy destroys all or most of the stem cells in bone marrow. This means that people can only have high-dose chemotherapy if the stem cells that are destroyed are replaced with healthy stem cells immediately afterwards.

What are the potential benefits of a stem cell transplant?

Good-quality studies have shown that some types of stem cell transplantation can help people with particular forms of cancer to live longer, or even overcome their cancer. This is true, for example, in people with certain forms of acute leukemia who have a transplant where the stem cells are taken from a donor who is related to them. Whether or not a person might benefit from stem cell transplantation depends on various factors, though, so it is not possible to draw any general conclusions about the benefits and harms of stem cell transplantation at this point. You can talk to a specialist doctor about the possible advantages and disadvantages of this treatment in your personal case.

When is a stem cell transplant considered?

Stem cell transplantation is a very demanding and risky treatment that can lead to serious, sometimes life-threatening complications. Because of this, it is generally only considered if other treatments have failed or if the cancer is very likely to come back. Whether or not a stem cell transplant is possible will depend on various factors, such as the person’s age, state of health and whether a suitable donor has been found. Even if stem cell transplantation is possible from a medical point of view, it is a good idea to find out about the advantages and disadvantages of this kind of treatment before making a decision.

What happens during a stem cell transplant?

Before a stem cell transplant is done, doctors do a series of tests to get a clearer picture of the disease and to make sure that the person is physically fit enough to have a stem cell transplantation. In addition, a catheter is placed into one of their large veins (central venous catheter). This is then used to take blood samples, give chemotherapy and transplant the stem cells.

The treatment itself usually starts with a so-called conditioning regimen. This involves high-dose chemotherapy and sometimes radiotherapy too, to destroy as many cancer cells in the body as possible. If the stem cells used in the transplant are taken from a donor, the conditioning regimen has another important function as well: it suppresses the recipient’s immune system so that his or her body is less likely to reject the transplanted stem cells. The conditioning regimen also destroys all or most of the stem cells in the bone marrow.

In order to replace the stem cells that have been destroyed, new stem cells are transplanted into the person’s body following the high-dose chemotherapy. The stem cells are fed into a vein using a drip, in a similar way to how blood transfusions are done. They reach the bone marrow within a few days and then start to make new blood cells. After four weeks people are usually able to make enough blood cells themselves again. Until then, they are given blood cells and blood platelets through blood transfusions.

What are the different types of stem cell transplantations?

In stem cell transplantation, the stem cells used can either be taken from the person having the treatment or from someone else (a donor). This is an important difference because donor stem cell transplants are associated with particular risks. There are also a few newer methods.

Autologous stem cell transplantation involves using a person’s own stem cells
 
When a person’s own stem cells are used for transplantation, the stem cells are taken from their body and frozen before their conditioning regimen starts. The cells are then transplanted back into their body after this treatment. This is only done if there are as few cancer cells as possible in their body when the stem cells are first taken. Because of this, people who have an autologous stem cell transplantation need to have chemotherapy before stem cells are taken from their body. The big advantage of autologous stem cell transplantation is that the body will definitely accept the transplanted stem cells. Even though it cannot completely ruled out that  some diseased cells might get back into the body together with the stem cells, this therapy can still be successful in some people.

Allogeneic stem cell transplantation involves using the stem cells of a donor

Stem cell transplantations using donor stem cells are carried out in a similar way to autologous stem cell transplantations. Using the stem cells of a donor has two advantages, but it also has a big disadvantage. One advantage is that particular immune cells are transplanted along with the donor’s stem cells, and these can help to fight any remaining cancer cells in the recipient’s body. This beneficial effect is called the “graft-versus-leukemia effect” or “graft-versus-tumor effect”. Another advantage is that there are no cancer cells among the transplanted stem cells because they are taken from a healthy person.

The disadvantage of using donor stem cells is that some of the donor’s immune cells that are transplanted might attack cells in the recipient’s body. This reaction, called graft-versus-host disease (GVHD), can damage tissues in the body. The skin, bowels and liver are the most affected. Acute graft-versus-host disease has four degrees of severity. A mild reaction (stage 1), for example, can cause a skin rash but does not influence the success of the transplantation. But more severe reactions (stages 2 to 4) can lead to serious, sometimes life-threatening problems needing intensive treatment.

Sometimes rejection reactions last a long time, or only start after a few months. This is called chronic graft-versus-host disease. It is an immune response that is similar to an inflammation, affecting tissues in the recipient’s body. Although it does not affect the production of new blood cells, it can cause several serious and very distressing problems, such as breathing difficulties, joint ache, diarrhea and problems with the mucous membranes, skin or eyes. The liver and other organs are sometimes affected too. People who have a chronic rejection reaction might have to take long-term medication.

To try to prevent a severe transplant rejection, it is important to find a stem cell donor whose tissue type matches the recipient’s tissue type as closely as possible. The ideal donor would be an identical twin whose tissue type is exactly the same as the recipient’s. But this is only very rarely the case. Other close relatives are considered as donors otherwise. If there is no suitable related donor, unrelated persons can also donate blood stem cells. Here, too, the donor’s tissue type should be as similar as possible to the recipient’s tissue type.

A number of national and international databases have been set up to help people find suitable stem cell donors. People who would like to donate stem cells can register with a database. In Germany, for example, the German Bone Marrow Donor Center (German: Deutsche Knochenmarkspenderdatei, DKMS) helps people find suitable donors. Their database contains information about more than 2 million voluntary donors. The German Registry of Bone Marrow Donors (German: Zentralen Knochenmarkspender Register Deutschland, ZKRD) in Ulm coordinates the cooperation between the various national and international databases.

One form of allogeneic stem cell transplantation is called reduced-intensity or non-myeloablative therapy. This is also sometimes called a mini-transplant. Here the chemotherapy is given at lower doses so that it does not completely destroy the stem cells in the recipient’s bone marrow. The problem with this is that some of the tumor or leukemia cells are left over in the body. But it is hoped that the remaining cancer cells will be destroyed by certain immune cells that are transplanted together with the donor’s stem cells. Mini-transplants are less demanding on the body and are associated with fewer complications. They are mainly used in people who would be very likely to have complications if the cells in their bone marrow were completely destroyed.

In-vitro manipulation

With both autologous and allogeneic stem cell transplantation there is a risk that some of the transplanted cells might damage tissues in the recipient’s body. Nowadays it is possible to prepare stem cells in a laboratory before they are transplanted, removing the cells that could be dangerous. This is called in-vitro manipulation.

What are the potential adverse effects and complications of stem cell transplantations and what can be done against them?

Each type of stem cell transplantation has its own specific advantages and disadvantages, as described above. There are also some complications that could arise with every type of stem cell transplantation, as well as a treatment-related risk of mortality. Several factors influence these risks, including the exact underlying disease and the treatment used. The risks are usually related to the fact that high-dose chemotherapy practically destroys all of people’s own blood cells. This means that their blood is unable to do its job properly for some time, until the transplanted stem cells have made enough mature blood cells.

The low number of white blood cells in the body means that the risk of infection is particularly high. Bacteria that normally live on our skin and in our bodies and are usually good for us can then cause infections. To stop this from happening, people often take antibiotics for prevention.

Because high-dose chemotherapy also reduces the number of blood platelets, people might experience bleeding, such as bleeding gums or nose bleeds. Sometimes the bleeding is more serious. To prevent this, regular tests are done to monitor the number of platelets in the blood. If there are too few, people can have a transfusion to get more platelets.

The number of red blood cells decreases during chemotherapy too. That is one of the reasons why people feel very tired and exhausted for some time after they have had this treatment. Here, too, the number of red blood cells can be increased through a blood transfusion, supporting the body and relieving the symptoms of anaemia.

Because their immune systems are weakened, most people get mouth sores (mucositis) during chemotherapy. This adverse effect is usually caused by a fungal infection and is normally very unpleasant and painful. It can become difficult to swallow and take much of the joy out of eating. The treatment might also result in hair loss.

Other possible complications include graft-versus-host disease, as described above, blockage of the hepatic (liver) veins, and femoral head necrosis. The therapy and its consequences can be very distressing overall. Cancer wards sometimes have clinical psychologists who offer emotional support for people who have cancer. One possible late effect of high-dose chemotherapy is infertility. Women and men who would like to have children need to talk to a fertility specialist doctor.

What can be done to help people cope with the treatment?

Stem cell transplantation is a very demanding treatment, both physically and emotionally. It involves a lot of time in hospital and facing a lot of tests and treatments. Everything revolves around the disease, and for most people it is a time filled with anxiety and worries about the future. This is often not only very distressing for the person having the treatment, but also for their family and other people close to them. Many people find it helpful to talk to others who are in a similar situation, for example in a self-help group. Meeting someone who has had a successful stem cell transplant in the past could also help some people stay positive and look to the future with optimism. Last but not least, special psychological support for people with cancer (psycho-oncology) can be helpful too.

Because people are more likely to get infections in the first few days or weeks following a stem cell transplantation, they usually have to spend this time in medical isolation to avoid germs. This is often the hardest part of therapy. Their body is still very weak, and they are only allowed a limited number of visitors because of the risk of infection. Many people feel powerless and helpless during this time. There are various things that people can do to try to cope with this situation and these depressing feelings. Some find a daily routine helpful, such as talking to their friends and family on the phone, or writing letters and emails. In this way they can stay in contact with the people they are close to, helping them to feel less isolated. Others find strength in faith and religion. Taking personal things such as photos into the hospital can also help to create a more familiar atmosphere and make the hospital stay as pleasant as possible.

This treatment can make people feel very lonely sometimes. How do other patients cope during this very difficult time? They often say that staying positive and concentrating on the future helped them. Many patients also say that their family and friends gave them strength.

If you would like more information on cancer and cancer treatments, or if you are looking for self-help groups or other forms of support, you can contact the free German Cancer Information Service (Krebsinformationsdienst) hotline (in German) at 0800 – 420 30 40 in Germany.

Related topics: here

This additional information has been provided by the U.S. National Library of Medicine:

In the U.S., the National Cancer Institute provides cancer information specialists, Monday through Friday, 8am to 8pm, Eastern Time at 1-800-4-CANCER (1-800-422-6237). Also in the U.S., the National Marrow Donor Program (NMDP) maintains an international registry of volunteers willing to be donors for all sources of blood stem cells used in transplantation: bone marrow, peripheral blood, and umbilical cord blood. http://www.marrow.org

Author: German Institute for Quality and Efficiency in Health Care (IQWiG)

© IQWiG (Institute for Quality and Efficiency in Health Care)