What is a stem cell transplant?
A transplant basically refers to the transfer of tissue between two organisms, the donor and the recipient. The donor and recipient can be the same person (autologous transplantation) or two different people (allogeneic transplantation). This is also the case with stem cell transplants – a form of therapy that is used for various cancers and serious diseases of the blood and immune system.
Stem cells are undifferentiated cells that can divide indefinitely. When they divide, a new stem cell and a cell capable of differentiation are created – i.e. a cell that can develop into a specific cell type (e.g. skin cell, blood cell).
- the red blood cells for oxygen transport (erythrocytes)
- White blood cells for immune defense (leukocytes)
- platelets for blood clotting (thrombocytes)
Hematopoietic stem cells are found in the bone marrow of various bones – especially in the bone marrow of the long tubular bones, the pelvis and the sternum. The formation of blood cells (hematopoiesis) is coordinated in the bone marrow by a number of different hormones. The finished cells are then flushed out into the blood.
Treatment with other types of stem cells has so far largely only been carried out in experimental studies.
Hematopoietic stem cell transplantation
If the patient’s own stem cells, which were removed before cancer treatment, are (re)transplanted, this is referred to as an autologous stem cell transplant. However, if the donor and recipient are two different people, it is an allogeneic stem cell transplant.
Doctors around the world perform more than 40,000 hematopoietic stem cell transplants every year. The treatment is necessary for patients with diseases of the hematopoietic system, such as leukemia.
Autologous stem cell transplantation
In autologous stem cell transplantation, the patient is their own donor. The procedure is therefore only suitable for patients with healthy bone marrow.
First, the doctor removes healthy stem cells from the patient in order to freeze them until they are transferred back.
Allogeneic stem cell transplantation
In allogeneic stem cell transplantation, hematopoietic stem cells from a healthy donor are transferred to a patient. As with autologous stem cell transplantation, the patient undergoes myeloablation to remove their own stem cell tissue from circulation. In addition, the patient is given medication to suppress their immune system (immunosuppression) so that it cannot fight too strongly against the foreign stem cells that are later transferred.
After this preparation, the blood stem cells previously removed from the donor are transferred to the patient.
Due to the large number of potential donors (there were already around five million in Germany in 2012), the search is now successful in over 80 percent of cases.
Mini-transplantation
A new development is stem cell transplantation without high-dose therapy (“mini-transplantation”). This involves significantly weaker myeloablation (i.e. less intensive chemotherapy and radiotherapy), which does not completely destroy the patient’s bone marrow. This procedure is used, for example, for patients who suffer from a poor general condition and would therefore hardly survive high-dose chemotherapy and whole-body radiation. However, this procedure is not yet standard and is reserved for studies.
There are different areas of application (indications) for autologous and allogeneic stem cell transplantation. In some cases, the indications overlap – which type of stem cell transplant is then used depends on various factors, for example the stage of the disease, age, general condition or the availability of suitable HLA-compatible donors.
In general, there are the following areas of application for autologous and allogeneic stem cell transplantation:
Autologous stem cell transplantation – application
- Hodgkin’s and non-Hodgkin’s lymphomas
- Multiple myeloma (plasmacytoma)
- Neuroblastoma
- Acute lymphoblastic leukemia (ALL)
- Acute myeloid leukemia (AML)
Lymphoma and multiple myeloma are the main areas of application for autologous stem cell transplantation.
- Acute lymphoblastic leukemia (ALL)
- Acute myeloid leukemia (AML)
- Chronic lymphocytic leukemia (CLL)
- Chronic myeloid leukemia (CML)
- Osteomyelofibrosis (OMF)
- Non-Hodgkin’s lymphoma
- Severe congenital diseases of the immune system (immunodeficiencies such as severe combined immunodeficiency, SCID)
- Congenital or acquired disorders of blood formation such as aplastic anemia, thalassemia and paroxysmal nocturnal hemoglobinuria (PNH)
What does a stem cell transplant involve?
Obtaining stem cells
Hematopoietic stem cells can be obtained from three sources:
Bone marrow
The stem cells are taken directly from the bone marrow (hence the original term “bone marrow donation” or “bone marrow transplantation”). The pelvic bone is usually chosen to aspirate some bone marrow blood via a hollow needle (puncture). Compared to peripheral blood (which circulates in arteries and veins), it has a higher proportion of white blood cells (leukocytes) and their precursor cells – including the desired stem cells. The red blood cells it also contains can be separated and returned to the donor’s body – this minimizes blood loss.
Blood
Stem cells are obtained from peripheral blood, i.e. blood that is not in the bone marrow. As it contains fewer stem cells than bone marrow blood, the patient is injected with a growth factor under the skin for several days beforehand. This stimulates the blood stem cells to increasingly migrate from the bone marrow into the blood. A type of blood washing (stem cell apheresis) then takes place – the peripheral stem cells are filtered out of the venous blood using a special centrifuge device.
Disadvantages: The administration of the growth factor can significantly increase the number of white blood cells, which can be associated with bone pain. In addition, two sufficiently large vein accesses must be made to collect the peripheral stem cells – some donors react to this with side effects such as circulatory problems and headaches.
In addition, a peripheral stem cell transplant is more likely to cause a type of rejection reaction (graft-versus-host disease, see below) in the recipient than a transplant of stem cells from other sources.
Umbilical cord
It does not make sense to keep your own child’s umbilical cord blood in case they need a stem cell transplant later on. According to current knowledge, it is not suitable for an autologous transplant. In addition, the probability that a child will need its own stem cells at some point in the future is very low.
Stem cell transplant procedure
The process of a stem cell transplant is roughly divided into three phases:
- Conditioning phase First, the bone marrow with the tumor cells is destroyed by chemotherapeutic agents or total body irradiation, thus “conditioning” the organism for the new stem cells. This phase lasts between 2 and 10 days.
What are the risks of a stem cell transplant?
Characteristic and sometimes serious complications can occur in all phases of stem cell transplantation.
Side effects of conditioning
Chemotherapy and/or total body irradiation during the conditioning phase can lead to considerable side effects. These can affect the heart, lungs, kidneys and liver. Hair loss and inflammation of the mucous membranes are also common.
Infections
Infections are also possible after discharge from hospital. Patients are therefore often given preventative medication against bacteria (antibiotics), viruses (antivirals) and fungi (antifungals).
Transplant rejection
A reaction of the recipient’s immune system against the transplanted stem cells can lead to a rejection reaction. This classic form of organ rejection is also known as donor-versus-recipient reaction (host-versus-graft disease). Depending on HLA compatibility, this occurs in 2 to 20 percent of all allogeneic stem cell transplants. If laboratory values indicate transplant rejection, the patient receives medication that strongly suppresses the immune system (intensive immunosuppression).
- Acute GvHD (aGvHD): This occurs within 100 days of allogeneic stem cell transplantation and leads to a skin rash (exanthema) and blistering, diarrhea and elevated bilirubin levels as a sign of liver damage. Around 30 to 60 percent of all allogeneic stem cell transplants result in aGvHD. The risk is higher for unrelated donors than for related donors.
Chronic GvHD can develop from acute GvHD – either directly or after a symptom-free intermediate phase. However, it can also occur without any previous aGvHD.
To avoid GvHD, the stem cells are filtered after collection to remove the T lymphocytes as far as possible (leukocyte depletion). Various drugs to suppress the immune system (including steroids, cyclosporine A or tacrolimus with methotrexate) are used for the prophylaxis and treatment of both forms of GvHD.
What do I need to consider after a stem cell transplant?
It is important that you pay attention to possible side effects: Immunosuppressive therapy often causes inflammation of the mucous membranes, nausea, vomiting and diarrhea, for example. These side effects can lead to you eating less (e.g. inflamed oral mucosa, nausea) or your body not being able to absorb enough nutrients (in the case of vomiting and diarrhea). They must therefore be treated. In extreme cases, artificial nutrition may be necessary to ensure an adequate supply of nutrients.
After you have been discharged from hospital, there are a few things you need to bear in mind to protect yourself from infection or transplant rejection. Until your immune system has recovered:
- Take your medication regularly.
- If possible, avoid crowds (cinema, theater, public transport) and contact with sick people around you.
- Stay away from building sites and avoid gardening, as spores from soil or building rubble can lead to dangerous infections. For the same reason, remove houseplants with soil and avoid contact with pets.
- Do not have any vaccinations with live vaccines.
- You do not have to follow a special diet, but certain foods are not good for you because of their increased risk of germs. This applies in particular to raw products such as raw milk cheese, raw ham, salami, leafy salads, raw eggs, mayonnaise, raw meat and raw fish.
You should also attend the regular follow-up appointments offered: Your attending physician will examine you and take blood samples to check your blood values and drug concentrations.
In most cases, you can return to work three to twelve months after the stem cell transplant.
