(BONE MARROW TRANSPLANT – PERIPHERAL STEM CELL TRANSPLANTATION)
WHAT IS A CELL? : They are the smallest living parts of our body. They can only be seen with a microscope. They come together to form “organs and tissues”; liver, heart, stomach, spleen, tissue etc. as. The structure and function of cells in each tissue or organ is different, they were produced specifically for that job.
Hematopoiesis: “Formation of blood cells”Hematopoietics: “Blood forming cells”
HEMATOPOETIC STEM CELL: It means “blood-forming mother cell”.
Blood cells are made only in the bone marrow. There are three types of blood cells: 1- Red blood cells – red blood cells (erythrocyte) 2- White blood cells – white blood cells (leukocytes) 3- Platelets (blood platelets)
These cells are formed by the “parent / progenitor cells” in the bone marrow. It is produced and released into the bloodstream when maturation is complete. The blood-forming mother cells are called “HEMATOPOETIC STEM CELL”. Their number is constant, but when necessary, they can both increase their number and produce new and mature blood cells. Stem cells and the number of mature blood cells they produce are under very careful control, these numbers do not change under normal conditions.
Functions of blood cells:
1- Red blood cells (red blood cells): They carry energy, heat, oxygen, nutrients and everything they need to all body cells. They also take back the leftovers. The decrease in red blood cells or the oxygen-carrying hemoglobin they contain is called “anemia”; causes weakness, fatigue, palpitations, pallor. The tasks of all body organs begin to fail.
2- White blood cells: They protect our body against all kinds of infections (inflammation caused by microbes). The reduction of these cells can lead to serious infections and even death.
3 – Platelets: The most important job in our body is to prevent bleeding. When their number decreases, bleeding may occur from various places: gingival, nose, stomach, brain, skin bleeding.
If the bone marrow, whose task is to produce blood, begins to function defectively or becomes inoperable for any reason, decreases are observed in red blood cells, white blood cells and platelets in the circulating blood. Normal blood cells gradually decrease.
1-Bone marrow may produce defective due to its unique disorders: As in leukemias (bone marrow cancers).
2- Or diseases in other parts of the body may spread to the bone marrow (such as the spread of different organ cancers to the bone marrow).
3- Or, it can reduce or stop its production without any reason (such as aplastic anemia)
In all these cases, “stem cell transplantation” may be required.
How are stem cells collected?
1- It can be collected from the donor’s bone marrow with special needles under anesthesia.
2- There are stem cells in the circulating blood, they can be collected from the vein by a special device. Here, the person simply lies in a resting position for a while, as if giving blood, with an IV set attached to his arm. It does not cause pain or discomfort, it is an easy procedure. Before the procedure, a needle is given to the donors to increase the number of stem cells under the skin for a while. No operating room conditions are required.
Collected cells are stored in liquid nitrogen at -196 degrees, thawed when necessary, and given intravenously to the recipient.
What are the stem cell sources?
1- Bone marrow,
2- Circulating blood in the veins,
3- Umbilical cord (the baby’s stem cells can be taken from here during birth)
Stem cells How many types of applications?
1 Allogeneic stem cell transplantation: Transplant from another person.
2 Autologous transplantation: The marrow taken from the person is given to him again.
3 Syngeneic transplant: Transplant from twin siblings.
4 Unrelated transplant: Transplant from unrelated people.
Which diseases require hematopoietic stem cell transplantation?
It is tried in countless good and bad diseases, sometimes even congenital diseases. This application is a type of treatment and does not always provide healing for every patient. During or after the application, the patient may be lost and the disease may recur. The person’s main disease may be cured, but other significant permanent damage may occur. These should be well known to the buyer.
The places where it is most applied today:
1 – Leukemias that we can call bone marrow cancers,
2 – Hodgkin’s disease and Non-Hodgkin lymphomas, which are lymph node cancers,
3 – Various organ cancers (such as breast, testicle, lung cancer)
4 – Situations where the bone marrow works poorly or does not work (such as aplastic anemia).
WHAT ARE MAJOR PROBLEMS?
The recipient’s immune system (immune system) rejects the given marrow, the new marrow cannot multiply and function. We call this the “engrafman” – patch- failure. Patient; confronts with deadly dangers such as bleeding and infection. Bleeding due to platelet deficiency and infections due to low white blood cells may occur during the time that the donated stem cells settle and start working. Since the person’s defense system has been destroyed before, serious and fatal infections may occur, and patients may be lost from the infection despite the antibiotics given.
More importantly, starting from the first 10 days, “acute graft versus host” disease (AGVHD) may develop. That is, some of the new healthy cells introduced perceive this new environment as foreign and begin to harm the new vulnerable body. So, in a sense, the donor rejects the receiver. In this case, it primarily targets the intestines, liver, skin and lungs. Diarrhea, bloody diarrhea, jaundice, red flakes on the skin, sores may occur. All skin can be peeled off. Respiratory failure may develop. These problems may or may not be overcome with external support treatment, and may lead to death of the patient.
The patient may develop “Chronic GVHD” months after discharge or in the weeks following transplant. This situation means that the immune system of the person is weakened and completely vulnerable. So, easily, it gets infected. For example, he may die from a simple “herpes” or throat infection. Or he may need to be hospitalized for a long time. B- It may also cause significant liver damage. C- The recipient’s mouth and eyes become dry, all secretions decrease. Starting from the mouth, both the secretions decrease and the soft inner surface becomes a dry hard tissue throughout the entire intestines. The stomach and intestines cannot work well. D- All muscles become stiff, the patient has difficulty in moving his joints, it is as if he is wearing armor. E- The patient’s sexual activity decreases, most likely his ability to bear children is lost. F- The skin turns brown. Inflammatory events may develop in the eye, which can lead to loss of vision.
In addition to all these, various side effects related to the drugs used may occur and further aggravate the picture.
Here, it is very important to know and understand all these possibilities when deciding on a stem cell transplant. For this purpose, following a very good psychological support and treatment plan increases success. The success rate, even healing, is around 50%.
This is also a significant number. Secondary cancers may occur years later, for example 7-10 years, due to the drugs and radiation therapy used.
What is allogeneic stem cell transplantation and how is it done?
1- Necessary health screenings are done for the patient (recipient) and donor. Make sure that both are not exactly “visible” health problems. One point may come to mind here; If the recipient is healthy, why make AKT? 1- Although the recipient’s blood and bone marrow appear normal in the examinations, the first chemotherapy cannot destroy all leukemia / cancer cells. There are still cancerous cells in his body that we cannot see. Therefore, the disease reappears (relapses) after a while. 2- If we increase the doses of drugs we use during chemotherapy, all cancerous cells can die. However, the bone marrow and other tissues are irreparably damaged. Therefore, without a healthy bone marrow support/refill, we cannot increase drug doses enough to destroy all cancerous cells. This backup/support is a “healthy new marrow”. It cannot be used here, especially in leukemia, for concern that one’s own marrow may contain residual diseased cells. In other words, autologous transplantation is not suitable. Otherwise, the disease may recur!
2 – If the receiver and transmitter are healthy, the transactions start;
A) A catheter is attached to the recipient that will remain permanently and will not disturb him. That is, a permanent thin tube is placed in a suitable vein. If necessary, blood can be taken from here and all medications can be given. There is no problem of frequent venipuncture.
B) The patient is given a high dose of anticancer drug called “preparation regimen”.
The reasons for this are several:
1 – Kills cancer cells left in the recipient.
2 – Silences the protection/defense systems in the receiver’s body. Thus, it prevents the rejection of the new and healthy stem cells introduced. By destroying the person’s unhealthy marrow, it opens a place for new and healthy stem cells.
C) Stem cells collected from the donor are given intravenously to the recipient on the same day or later. This delivery takes place immediately after the priming regimen.
Patient (recipient); must stay in a separate room (a special care unit) both during and after the preparation regimen and the transplant of stem cells! In this way, the contamination of various microbes and lethal inflammations (infection) can be prevented.
Usually, 14-15. day the new marrow settles in its place and starts to work. However, this period can be much longer. It may be necessary to stay in the unit for 4-5 weeks. Under normal conditions, the person can be discharged from the hospital in 1.5 months.
The above operations may not always go well! Bone marrow, stem cell transplant, as we call it today, is not an easy process as it is in the movies or in the press. In particular, the days, months after transplantation are very gentle. Short or long-term, very serious problems may occur. Transplantation can end in death.
AUTOLOGICAL STEM CELL TRANSPLANTATION (OKHN), that is, the process of giving one’s own stem cells to oneself is a very different approach.
Application areas
Lymphomas (cancers of lymph nodes), Solid tumors: Organ cancers other than bone marrow such as breast, lung, ovary, testicular, etc. cancers are the main application areas. It is sometimes used in well-selected patients with acute leukemia who do not have a suitable donor. The first treatment options for these diseases are chemotherapy (special cancer drugs) and radiotherapy (radiation therapy). Or both are used together.
However, these treatments do not always eliminate the disease, the disease may recur, or the first treatment is partially beneficial. If the dose of the drugs used is increased, the disease can be stopped. Here is your problem; It is the destruction of the main blood-producing cells in the bone marrow of the person along with the cancer cells when the drug doses are increased enough to eliminate the cancer. The person’s cancer disappears, but because the bone marrow cannot produce blood, a very serious and irreversible bone marrow deficiency occurs. Bleeding, infections, severe weakness, exhaustion, anemia-related disorders in the whole body lead to death. That’s why autologous transplantation (OKHN) has come to the fore.
The logic and practice followed in OKHN are as follows:
1- If the bone marrow of the person is clean, that is, if the existing cancer has not spread to the bone marrow, their own stem cells are collected. These stem cells are collected either directly from the marrow or from the circulating blood. So it is just like AKHN.
2- These cells are stored frozen at -80 degrees (in liquid nitrogen tank).
3- Medicines used for cancer in the patient and known to be effective are given in very high doses. This dose is high enough to destroy cancerous cells. However, care is taken to ensure that doses are not harmful to organs such as the heart, liver, lungs and kidneys. The high-dose drug destroys the cancerous tissue, meanwhile the patient’s bone marrow is destroyed. The blood-forming stem/mother cells of the person we back up are ready in our hands. After high-dose chemotherapy, his own stem cells are given back to him. It takes 10-20 days for them to settle back into place and start working.
In this type of transplant, there are not as many problems as in AKHN.
1- There is no obligation for a separate and special unit. It can be done in a single room, apart from the bone marrow unit. Again, extreme attention is paid to cleanliness. body cleansing; mouth, teeth, skin, needle and catheter entry points, hand cleaning are basic conditions.
2- AGVHD and Chronic GVHD are not seen.
3- White blood cells and platelets recover more quickly, that is, engraftment (settlement) becomes quicker and less problematic.
Engraftment failure is a less common condition than AKHN. An important condition for success is the absence of cancer cells in the given marrow. If the cancer has spread to the bone marrow, the disease recurs quickly because it will be in the collected cells, in the cancerous cells. The benefit of OKHN in such patients is limited. An important condition for success is that the cancer tissue in the patient must still be sensitive to drugs. If the cancer cells are not sensitive to the drug to be used, high doses will not be beneficial. On the contrary, it will harm the body.
OKHN is not a sure cure, but it can give very successful results. This is also true for AKHN, as stated above.
Unrelated transplants
Stem cell transplants from unrelated people to people who do not have a suitable sibling or first-degree relative donor. In these transplants, the problems seen in AKHN occur much more frequently and severely. Even if the tissue type is 100%, this high risk is valid. The use of a race other than one’s own adds risk to risk. The success rate is low and the risk of death is high. This option definitely requires the patient to be very willing. Also, the cost is very high. Screening hundreds or even thousands of volunteers takes a lot of time and money even before transplantation. Since the post-transplantation problems will be too many, their treatment will increase the cost several times and complicate the situation. The risk of death can be up to 80%. In conclusion, in unrelated transplants, the benefit/harm discussion should be done very well, and the patient and his family should know them very well. It should consider failure and loss of patient in advance.
In all transplants, patients and families must prepare themselves for a new life, knowing that they are going through a long and difficult battle, at least for a long time, that their lives will be completely changed. families; It is necessary for them to realize that they have stepped into a life style that will constantly meet with the doctor and the hospital, have examinations every day, and put other socioeconomic problems in their life to the background. Their living places will also change in parallel with this. In other words, not only the patient, but also family members should accept that they can be socioeconomically damaged in this event. In the old parlance, “Bone marrow transplant” is not a miracle approach that simply ends with the exchange of marrow cells. On the contrary, it is a chain of treatments that includes many forms of treatment and requires a large number of specialist doctors and laboratory services. It includes both life and death. Despite these difficult realities, some patients have benefits that are incomparable with other options. If the timing is well done, the technical possibilities are sufficient, the patient’s performance is very good, and there is a suitable donor (in ACHN), the results can be very pleasing in good centers.
THIS ARTICLE WAS WRITTEN USING THE www.thd.org.tr website. IF YOU WANT MORE DETAILED AND ACCURATE INFORMATION, YOU CAN REFER TO THIS SITE.
