General medical information

Stem cells need to be harvested before a stem cell transplantation can be carried out. Stem cells are the cells in the bone marrow that red and white blood cells and platelets develop from. These cells are characterised by their capacity for self-renewal. In a transplantation procedure, they can either come from the patient themselves or from a sibling match or non-familial donor. Donor cells are infused intravenously into the bone marrow cavities, where they mature and become different types of blood cells.
If the patient donates their own stem cells, the transplantation is what is known as autologous. This type of procedure is only possible, however, if as few tumour cells as possible – ideally none whatsoever – are present in the body at the time that the stem cells are harvested. Transfer of stem cells from one person to another is called allogeneic transplantation. The transfer of stem cells from children to parents (or niece to aunt and vice versa etc) is called haploidentical or half-match transplantation. These different forms of transplantation are the standard treatment for numerous diseases.

The stem cells used in a transplantation can be obtained from various sources:

Bone marrow
This is where stem cells are produced. To ensure that the transplanted stem cells respond properly in the recipient, 2-3 x 108 nucleated cells per kilogramme of the recipient's body weight must be harvested, which usually corresponds to 10-15ml per kilogramme of body weight. This is usually accomplished by means of a large number of punctures at the posterior iliac crest. As this procedure can be painful for the donor, it is usually performed under general anaesthetic. On rare occasions, spinal or epidural anaesthesia may also be used. The risk for the donor is low, and only very rarely associated with complications due to the anaesthetic, local infections, haematomas, post-operative fever and – in extremely rare cases – complications due to fracture of the pelvic bone.

Peripheral blood stem cells (currently the most commonly used stem cell source)
Additional "tricks", such as the administration of a growth factor for white blood cells, can be used to introduce stem cells into the blood even though they are usually only present in sufficient numbers in the bone marrow. These stem cells exhibit a surface feature called CD 34, which can be used to measure the stem cells in the blood. If enough of these CD 34 positive cells are present in the blood, they can be harvested through a catheter at the unit’s transfusion centre. If the donor’s veins are deemed to be very good, the procedure can be performed via a vein in the arm. Otherwise, a central venous catheter must be inserted. This is usually carried out under localised icing in the hospital’s intensive care unit. The stem cells are then ready for harvesting. As soon as enough stem cells have been collected to safely perform a transplant, the harvesting procedure is ended. Stem cells are then frozen at -185°C for a scheduled autologous transplant. At this temperature, stem cells can be stored for more than 10 years without losing functionality.
In the case of allogeneic transplantation, blood stem cells are obtained from healthy donors, likewise following pre-treatment with a growth factor (over the course of four days). Once collected, the donor cells are administered to the recipient without prior freezing. All donors are thoroughly examined before medication is administered, to eliminate health risks for donor and recipient alike.

The main pre-conditions for successful stem cell transplantation are good general health and vital organ function (heart, lungs, kidneys, liver). It is also important that you do not contract an infection immediately prior to starting the conditioning treatment, as the high-dose therapy causes a severe weakening of the immune system, which can cause infections to worsen very quickly, making them very difficult to treat. As a result, you will be required to undergo various examinations (dentist, ear, nose and throat specialist, gynaecologist, computer tomography of the lungs and abdominal organs, special blood tests) just before the scheduled transplant date to rule out the possibility of infection. Any sources of inflammation must be treated before you are admitted to the hospital for transplantation so that the infection risk is kept to an absolute minimum. It goes without saying that preparations for a stem cell transplantation and the procedure itself can only be carried out if you have given your verbal and written consent after in-depth consultations have been carried out (ideally in the presence of family members). Depending on the type of conditioning therapy, the upper age limit for allogeneic transplantation is between 50 and 70 years, and between 60 and 75 years for autologous transplantation.
For an allogeneic transplantation to be successful, it is extremely important that you and your donor are as close a match as possible for certain tissue characteristics (known as HLA antigens): serious immunological reactions can be triggered if multiple antigens are not a suitable match. In such cases, the new immune cells formed from the donor's stem cells can damage your organs. This complication is known as graft-versus-host disease, which is abbreviated to GvHD. Compatibility of tissue between you and your donor is determined by blood tests in specialist laboratories. The probability of a sibling match is 25%. If no tissue-matched siblings are available, a search is initiated in national and international registers for a non-relative volunteer donor.

Insertion of a central venous catheter
You will be given a central venous catheter before the start of treatment. This involves inserting a small plastic tube into a large vein in the neck under local anaesthetic. All of the blood samples are taken, stem cells infused and infusions (medication, nutritional solutions, trace elements) and blood products (red blood cells, platelet concentrates) administered via this catheter during your time at the hospital.

Administration of high-dose therapy (conditioning)
Conditioning is the high-dose treatment that is administered to eliminate residual leukaemia or tumour cells and suppress the patient's immune system. Their precise composition depends on the disease in question and the stage of the patient’s disease at the time of transplantation as well as their age and treatment history. Conditioning can take the form of chemotherapy on its own, or a combination of chemotherapy and whole-body radiotherapy. In the case of allogeneic transplantation, conditioning also serves to suppress the patient's immune system to help prevent the transplanted cells from being rejected.
The most common side effects of high-dose therapy are nausea, vomiting, diarrhoea, difficulty swallowing, dryness of the skin and mucous membranes, and hair loss. Patients are given preventative medication to guard against nausea and vomiting during and shortly after conditioning. If the mucous membranes in the mouth or oesophagus become raw and very painful, painkillers are administered as a continuous infusion. In order to prevent damage to the kidneys and bladder, large amounts of fluids are administered throughout chemotherapy. As a result, dehydrating agents may sometimes have to be administered to prevent excessive fluid build-up in the tissue. Despite all preventive measures, severe organ damage can occur as a result of conditioning, most of which can be reversed within a matter of weeks or months, but in very rare cases it can also lead to death.
High-dose whole-body irradiation also severely damages the gonads, resulting in infertility or sterility. If you wish to have children in the future, you will be offered the option of having your sperm or eggs frozen prior to transplantation. Allogeneic transplantation is also associated with a slightly increased risk of subsequent development of an additional tumour disease.

Measures during aplasia (no formation of blood cells)
The stem cells that are infused via the central venous catheter find their own way into the bone marrow cavities, where they settle after just a few hours, initially self-renewing before going on to form blood cells (red and white blood cells, platelets). However, it takes around two to three weeks for the new blood cells to be formed in sufficient numbers and to function properly. During this time, the levels of white and red blood cells, as well as platelets in the blood decrease sharply to begin with, which leaves patients highly susceptible to infections and bleeding during this period.
If levels fall below a certain threshold, you will be given a blood transfusion (red blood cells) and platelet concentrates. To minimise the risk of infection during this time, all patients are accommodated in single rooms. Patients at the highest risk of infection are accommodated in special rooms with a corresponding air filtration system. Anyone who enters the patient’s room during this phase must take the appropriate protective measures (gloves, face mask, apron) to prevent the transmission of infections.

Regeneration of the blood system
After autologous transplantation, it takes on average around 10-14 days until the "new" bone marrow produces larger quantities of blood cells, leading blood levels to rise again. For allogeneic transplantation, the average is two to four weeks. Following autologous transplantation, the granulocyte count (a subgroup of white blood cells that are particularly important for staving off infection) needs to be above 500 for a day before you can leave the sterile room. In the case of allogenic transplantation, the granulocyte count must be above 500 for three days.

Donor-versus-recipient reaction (graft-versus-host disease)
Despite careful scrutiny of tissue characteristics, the emerging immune cells that develop from the stem cells transplanted from the donor may identify the recipient's bodily cells as foreign and attack them, precipitating organ damage. This reaction is known as graft-versus-host disease (GvHD). To reduce the likelihood of this, patients are given immunosuppressive medication.

Patients can be discharged from the inpatient area once it has been established that they are fever-free after transplantation, can take their medication without any issues and blood levels for the medication are sufficient, the blood count has regenerated to such an extent that no more blood components need to be administered, and they can eat and drink sufficiently. Detailed consultations are conducted regarding post-transplantation behaviour and an initial appointment is made with the outpatient clinic after the transplantation. During the first three months, regular check-ups are required at the outpatient clinic at one to two-week intervals.

All of the necessary laboratory parameters are determined during these check-ups at the outpatient clinic. Initially required at an interval of one to two weeks, the gap between check-up visits is extended to once ever two to four weeks in the following months. The check-ups and how often they are required are tailored to the individual patient. Patients who have undergone an allogeneic stem cell or bone marrow transplant will be looked after at our aftercare outpatient clinic for the rest of their lives.

The patient’s role following stem cell transplantation
It is very important that any medication is always taken exactly at the intervals and doses prescribed. Generally speaking, as an allogeneic transplant patient, you can expect to take important medication (against donor-versus-recipient reaction and infections) for approximately four to five months after transplantation. After autologous transplantation, medication to guard against infections should be taken for approximately two to three months.

Bone marrow biopsy
Depending on the disease, it may be necessary to carry out bone marrow biopsies to assess the success of the transplant. We ensure that only absolutely necessary bone marrow biopsies are performed.

Vaccinations
For information on vaccinations for immunocompromised persons, please contact the Specialised Outpatient Clinic for Vaccinations, Travel and Tropical Medicine.

Having chemotherapy and/or radiotherapy prior to stem cell transplantation, as well as the administration of immunosuppressive drugs can be very challenging for patients during and after transplantation. Complications may include reduced overall physical ability and an increase in general fatigue. Physiotherapy, which patients are given throughout their BMT treatment, is used to counter this.

Patients receive in-depth nutritional advice during their time at the hospital and for a short period after they are discharged from inpatient care.