With a transfer of stem cells from the bone marrow, leukemia and other diseases of blood formation can be cured. A suitable donor is crucial for the success of the therapy.
- Stem cell transplantation is a treatment option for serious diseases of the blood formation system such as leukemia. For this, the bone marrow of a healthy person is transferred.
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In medicine, a transplant is the transplantation of tissue from a donor to a recipient. Hematopoietic stem cells are usually transferred during stem cell transplantation. This becomes necessary if the blood formation is disturbed. Because the recipient's entire bone marrow is destroyed prior to the stem cell transplant, this treatment is very risky for him and can only be considered if other therapies do not work.
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What are stem cells?
Stem cells are body cells from which different tissues or cells can arise. The blood-forming stem cells are also called hematopoietic stem cells. From them, the red and white blood cells (erythrocytes and leukocytes) and the platelets (thrombocytes) develop in the bone marrow. They are therefore a reserve of the body, from which missing blood cells are regenerated.
Hematopoietic stem cells are mainly found in the bone marrow of the iliac crest, sternum and in the large long bones, only a few stem cells circulate with the blood flow through the body. Therefore, they are mostly obtained from the bone market – a stem cell transplant is also called bone marrow donation or bone marrow transplant. If the stem cells are obtained from the blood like umbilical cord blood, one speaks of a peripheral blood stem cell transplantation.
Areas of application and forms of stem cell transplantation
Stem cell transplantation is most commonly used to treat various forms of leukemia. Blood formation is disturbed in this cancer, which leads to a deficiency of all types of healthy blood cells. Leukemia and related diseases are usually treated with chemotherapy or radiation – if these therapies are unsuccessful, stem cell transplantation is used. For example, this is the case with:
Acute myeloid leukemia (AML)
Acute lymphoblastic leukemia (ALL)
Myelodysplastic Syndrome (MDS)
Non-Hodgkin's lymphoma
Myeloma / plasmacytoma
Chronic lymphoblastic leukemia (CLL)
Chronic myeloid leukemia (CML)
Hodgkin's disease
When autologous and when allogeneic stem cell transplantation?
Blood stem cells can either come from a suitable donor (allogeneic) or from the patient (autologous).
In the autologous stem cell transplant the patient's own stem cells are removed and transferred again after treatment. This ensures that blood formation continues to function even after chemotherapy or radiation, since both treatments damage the bone marrow. Autologous stem cell transplantation is rarely used in the treatment of acute and chronic leukemia, but is mainly used in the treatment of multiple myeloma and lymphoma.
For the allogeneic stem cell transplantation the stem cells in the patient's bone marrow are completely removed and then replaced by stem cells from a healthy donor. In order that these are not rejected, certain tissue characteristics of the donor (so-called HLA characteristics) must match those of the recipient as completely as possible. Blood relatives are more likely to match than strangers, which is why the search for a suitable donor begins within the family. If there is no suitable donor there, the search is expanded to databases in which potential bone marrow donors are registered. Although the probability that the HLA characteristics of two strangers match 100 percent ranges from 1 in 20,000 to 1 in several million, thanks to the now large number of potential donors, this route is now successful in over 80 percent of cases.
Stem cell transplant procedure
In peripheral stem cell transplantation, the donor is given a special medication for five days. This causes stem cells to multiply and pass into the blood. The cells are removed on an outpatient basis as in dialysis. This procedure takes about three to four hours and sometimes has to be repeated the following day.
With classic bone marrow donation, about one to one and a half liters of bone marrow are taken from the donor under general anesthesia – mostly from the hip bone. This takes about an hour, and the hospital can usually be left the day after. The removed bone marrow will completely replicate in a few weeks.
On the recipient side, stem cell transplantation consists of two phases: conditioning and the actual transplantation.
Conditioning destroys the bone marrow
Before the healthy donor stem cells can be transferred, the patient's entire hematopoietic system must be destroyed. This process is called conditioning. It takes place about seven to ten days before the actual stem cell transmission. The patient is then already admitted to the clinic's transplant ward.
The bone marrow, or more precisely the blood-forming cells, can be destroyed in two ways: by strong chemotherapy with drugs that particularly damage the bone marrow, or by high-dose radiation to the entire body. In both treatments, the pathological, degenerate stem cells are also destroyed.
At the time of the actual stem cell transmission, the patient can no longer form new blood cells and only has an extremely weakened immune system. In addition, platelets are no longer formed and there is an increased risk of bleeding.
The relatively new intensity-reduced conditioning (RIC) is not so aggressive. The primary aim is to switch off the immune system in order to minimize the risk of rejection of the donor stem cells. After the transplantation, these should then take over the control of the degenerate cells. This type of conditioning is more suitable for older recipients because it is not so stressful for the body.
The transfer of stem cells
The actual transfer of blood stem cells is amazingly simple: They are administered as an infusion like a blood preserve. The cells find their way into the bone marrow automatically, settle there, multiply and gradually build up a new blood formation and immune system. This process takes about two to four weeks, in which phase infections with viruses, bacteria and fungi are life-threatening. Those affected are therefore treated in specially shielded rooms and protected as much as possible from infection by medication.
Risks and side effects of stem cell transplantation
In addition to the rejection of the new cells, the time between killing the old and functioning of the new defense system is particularly dangerous. Those affected are therefore in specially shielded rooms in the transplant clinic. They are also protected against infections with strong medication. Most can leave the clinic after about four weeks.
However, it takes up to two years for the blood and the immune system to fully recover. During this time, strict precautionary rules must be observed. This applies, for example, to the handling of food, where strict hygiene must be observed. In addition, plants and soil should be banned from the living area and crowds of people should be avoided at first.
The background to these measures is that the new defense system – similar to that of a newborn – first has to learn to deal with germs from the environment. This learning process is completed after about two years, and those affected can lead a completely normal life in every respect. To prevent the new immune system from attacking the transplanted body, they are dependent on taking lifelong medications that have a depressing effect on the immune system. These drugs in turn can lead to side effects and damage to the organism.
Graft versus host disease as a serious complication
After an allogeneic stem cell transplant – especially if there is a lack of agreement between donor and recipient – the transplanted cells can target the recipient's cells (GvHD or graft-versus-host reaction). This reaction mainly targets the recipient's skin, liver and intestines and can potentially be life-threatening. Basically, the acute is differentiated from the chronic GvHD reaction.
The acute GvHD reaction sets in during the hospital stay. In a lighter form, it can be treated with drugs that dampen the immune system (immunosuppressants). However, this also increases the risk of infection. In addition, it is highly desirable that the new defense system is directed against leukemia cells that may still remain in the body and that they are finally eliminated. Acute GvHD reactions often subside within about three months.
At a chronic GvHD response the new defense system responds to the recipient's body with a delay, but then continues to fight it. In this case, too, immunosuppressive drugs are used to control the immune response.
Infertility after stem cell transplantation
Conditioning has different consequences for women and men. At Women leads them to the death of the egg cells in the ovaries. After chemotherapy or radiation, they can no longer have children. At the same time, the production of the female sex hormones estrogen and progesterone is discontinued. The normal monthly cycle is absent, typical menopausal symptoms can arise. Younger women need to start hormone replacement therapy after conditioning to replace the missing estrogen.
In men, the transplant also leads to infertility, because conditioning kills the germ cells that produce sperm in the testes. The hormone balance, on the other hand, is not or only slightly affected, because the testosterone-producing cells in the testes survive chemotherapy or radiation largely without damage.
If there is an existing or unclear desire to have children, men can freeze a sperm donation before starting chemotherapy or radiation therapy, and women have egg cells put on ice. This process is called cryopreservation. If you want to have a child later, the sample can be thawed again. With the help of modern reproductive medicine methods it is then possible to fertilize an egg cell and thus conceive a child. Disadvantages include a long preparation time for removal and freezing as well as financial issues.
Relapse
In some cases, it can happen that degenerate, diseased cells survive the conditioning prior to stem cell transmission or (with an autologous donation) are introduced with their own bone marrow. Leukemia can therefore recur even after a successful stem cell transplant. In addition to treatment attempts with medication, it is possible in these cases to repeat the stem cell transplant – including renewed conditioning.
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