Stem cell transplantation for treating cancer

Our blood is about 50% liquid (blood plasma) and 50% blood cells. There are three main kinds of blood cells:

• The red blood cells (erythrocytes) transport oxygen and carbon dioxide.
• The white blood cells (leukocytes) protect our bodies from germs.
• The blood platelets (thrombocytes) help to clot our blood and heal wounds.

Blood cells only have a short life span. Some live for just a few days, while others die after a few months. That means that a healthy person's bone marrow replaces billions of blood cells every day, especially red blood cells. The blood stem cells take over this job (for short: stem cells). They are in effect the mother of all blood cells, from which all other blood cells develop.

Stem cells are mainly found in the bone marrow, but some are also in the blood itself. Bone marrow is a spongy tissue that is found inside certain bones, such as the hip bones.

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

A very strong, high-dose form of chemotherapy is used to treat certain types of cancer. This kind of chemotherapy destroys all or most of the stem cells in our bone marrow. The body is then immediately provided with healthy stem cells via the blood, which settle in the bone marrow and produce fresh blood cells.

The medical term for this is “hematopoietic stem cell transplantation” (HSCT). “Hematopoietic” means “blood-forming.” Stem cell transplantation alone is not actually a cancer treatment in its own right. Rather, it replaces the vital blood stem cells that have been destroyed by the high-dose chemotherapy.

But some types of stem cell transplantation can also help to directly combat cancerous cells, because the donor cells actively fight the few remaining cancer cells.

Stem cell transplantation takes a high toll both physically and emotionally, and it can sometimes lead to serious and even life-threatening complications. This is mostly due to the high-dose chemotherapy and the temporary deficiency of vital blood cells. That is why it is generally only carried out if other treatments were not successful or there is a high risk of relapse.

There are a number of factors that influence whether stem cell transplantation is possible, such as age and overall health, or the availability of a suitable donor. It is definitely a good idea to find out about the advantages and disadvantages of this kind of treatment before making a decision.

Before stem cell transplantation, doctors carry out a series of tests to get an accurate picture of the illness and to make sure that the patient is healthy enough to have a transplant. A central venous catheter (CVC) is also fitted in one of the larger veins.  This catheter is used for taking blood samples, giving chemotherapy and supplying stem cells.

The treatment itself begins with what is known as a conditioning regimen. That means that as many cancer cells as possible are destroyed using high-dose chemotherapy and where necessary additional radiotherapy.

The conditioning regimen also has another important function: It suppresses the recipient's immune system, making sure that their body does not reject the transplanted donor stem cells. The conditioning regimen also destroys all or nearly all stem cells in the bone marrow.

New stem cells are transplanted to replace those that have been destroyed by the high dose chemotherapy. Like with a blood transfusion, they are fed into a vein via a drip. The donated stem cells reach the bone marrow within a few days and start to make new blood cells. Within four weeks your body can then produce enough blood cells again. Until then can be given transfusions of red blood cells and platelets if you have a serious lack.

The stem cells used in stem cell transplantation can either be your own or someone else's (donor). That is an important distinction, because transplanting stem cells from another person poses particular risks. There are also a number of newer methods.

If your own stems cells are to be used for transplantation, they will be taken and frozen before treatment begins. They are then put back into your body after chemotherapy. This is only done if there are as few cancer cells as possible in your body when the stem cells are first taken.

If you have an autologous transplantation you will therefore need to have chemotherapy before the stem cells are taken. The major advantage of having autologous transplantation is that your body will always accept your own transplanted stem cells.

Even though there is no guarantee that some diseased cells might get back into your body together with the stem cells, this therapy can be successful in some people.

Transplantation of donor stem cells is carried out in a similar way to autologous transplantation. Allogeneic stem cell transplantation has two advantages, but also one major disadvantage.

One advantage is that certain immune cells are transplanted along with the donated stem cells, and these can help to fight any remaining cancer cells in the recipient’s body. This beneficial effect is called "graft-versus-disease effect." Another advantage is that no cancer cells will be transmitted because the stem cells were taken from a healthy person.

The disadvantage of this kind of transplantation is that the donor's immune cells might start to attack tissue cells in the recipient's body. This kind of reaction is called a "graft-versus-host effect."

It mostly affects the skin, the intestines and the liver. Acute graft-versus-host disease has four degrees of severity. A mild reaction (stage 1) can cause rashes, but will not affect the success of the transplantation. But more severe reactions (stages 2 to 4) can lead to more serious, sometimes life-threatening problems that need 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 tissue in the recipient’s body.

Although it does not affect the production of new blood cells, it can cause several serious and debilitating problems, such as breathing difficulties, joint ache, diarrhea and problems with the mucous membranes, skin or eyes. It can also affect other organs such as the liver. People with 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.

Stem cells from close relatives are a good alternative. 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 find suitable stem cell donors. People who would like to donate stem cells can register with a database. There are currently 29 databases responsible for registering donors in Germany. Their contact details can be found on the German National Bone Marrow Donor Registry (ZKRD) website. This central registry collects all data from the different donor databases and also coordinates cooperation with various international databases.

One form of allogeneic stem cell transplantation is called reduced-intensity or non-myeloablative therapy. 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 immune cells that are transplanted together with the donor’s stem cells. Non-myeloablative 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.

With both autologous and allogeneic stem cell transplantation there is a risk that some of the transplanted cells might damage tissue in the recipient’s body. 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.

Each type of stem cell transplantation has its own advantages and disadvantages. There are some complications that can occur with every type of stem cell transplantation, so there is also a risk of death from treatment. 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 causes the supply of new blood cells produced in the body to decrease. This phase isn’t over until the transplanted stem cells have made enough new blood cells.

The low number of white blood cells makes the body particularly prone to infection. Even the usually harmless bacteria that live on our skin and in our bodies can then cause infections. To stop this from happening, people often take antibiotics as a 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. The number of platelets in the blood is regularly monitored to prevent this. If there are too few, additional platelets can be added to the blood by transfusion.

The number of red blood cells also decreases during treatment. That is one of the reasons why people feel very tired and exhausted after chemotherapy. To relieve symptoms of anemia, it is also possible in this case to replace the lost red blood cells by transfusion.

Because their immune systems are weakened, most people get mouth sores (mucositis) during chemotherapy. This side effect is usually caused by a fungal infection and is often 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. The high-dose chemotherapy can also cause complications like blockage of the hepatic (liver) veins or femoral head necrosis.

One possible late effect of high-dose chemotherapy is infertility. Women and men who are planning on having children should therefore talk to a fertility specialist before having treatment.

The therapy and its consequences can be very distressing overall. Many cancer wards have psychologists who offer emotional support for people who have cancer.

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 support group. Meeting someone who has had a successful stem cell transplant in the past might also help some people stay positive and look to the future with optimism. Last but not least, special psychological (psycho-oncology) care can also be very helpful.

Because people are more prone to infection in the first few days or weeks after 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 you 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, writing letters and emails, or staying in contact via chats and social media.

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.

The treatment can make people feel very lonely at times. 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.