What is Stem Cell?
The main cell in the bone marrow that makes all blood cells is called a “stem cell”. Since the transplanted stem cells are often taken from the bone marrow, it is also popularly known as “bone marrow transplantation”. Stem cells can also be harvested from circulating blood and from the baby's umbilical cord (cord blood) during birth. The basic principle of stem cell transplantation is that a patient, after very high doses of chemotherapy or radiotherapy, receives blood-forming stem cells from the patient himself (autologous) or from a donor with a compatible tissue type (allogeneic). The main goal here is to eliminate the patient's unhealthy bone marrow cells or cancer cells with high-dose chemotherapy and then to regenerate healthy bone marrow through stem cells.
In general, there are two types of transplantation: autologous and allogeneic HSCT.
Autologous Stem Cell Transplantation
In childhood, it is often used as part of treatments for solid tumors such as lymphoma and neuroblastoma. Here the donor is the child himself. At a certain stage of the patient's treatment, stem cells are obtained from their own bone marrow or peripheral blood, often by apheresis, frozen and stored. After high-dose chemotherapy and/or radiotherapy, it is dissolved and returned to the patient through venous route. The aim here is to eliminate the existing disease with high-dose chemotherapy.
Allogeneic Stem Cell Transplantation
In this method, stem cells from a healthy and HLA-matched donor are administered to the recipient (patient) via venous route after a preparative regimen including chemotherapy and/or radiotherapy. Here, HLA tissue group matching between the patient and the donor is extremely important for the success of the transplant. Therefore, for a patient who needs a transplant, the HLA tissue group match of parents and siblings must first be tested. In patients who do not have a related donor, a screening process is initiated first in national and then in international bone marrow banks to find a matching donor. At the end of all these processes, haploidentical stem cell transplantation can be performed in patients for whom a donor cannot be found or who require urgent transplantation. The parents of every patient who cannot find a matched donor have at least 5/10 HLA tissue matching.
As a result, allogeneic transplants are classified according to the donor as follows.
• HSCT from a relative
HSCT from a sibling
HSCT from a non-sibling relative
Haploidentic HSCT
• HSCT from a non-relative
Unlike autologous transplants, in allogeneic transplants, complications such as graft versus host disease or rejection of donated stem cells can develop even if the donor's tissue group is fully matched. The drugs used in the preparative regimen are therefore not only intended to eradicate the underlying disease, but also to suppress the recipient's immune system so that a foreign stem cell can settle and multiply. In addition, immunosuppressive drugs such as Cyclosporine should be used for a long time after transplantation to prevent tissue rejection disease.
Stem Cell Sources
Bone Marrow-Derived Stem Cells
The standard accepted source of stem cells for stem cell transplantation is bone marrow. The bone marrow is harvested from the back of the pelvis under anesthesia. Most donors return to normal daily activities within a few days. After harvesting, the bone marrow regenerates itself in 4-6 weeks.
Peripheral Blood-Derived Stem Cell
In recent years, peripheral blood-derived stem cells have been used with increasing frequency, especially in transplants from adult donors. Under normal conditions, there are very few hematopoietic stem cells in the peripheral blood. In the period following chemotherapy, it has been shown that the number of precursor cells in the peripheral blood increases up to 20-fold, and the number of circulating stem cells increases even more with the help of drugs called growth factors. The circulating stem cells are separated from the donor's blood using special devices. Except for the separated stem cells, the remaining blood is returned to the person.
Cord Blood-Derived Stem Cell
Umbilical cord blood is harvested from the umbilical cord or placenta after the baby is born. This blood is rich in blood-forming cells. Donated blood is tested for various aspects and stored for future use when needed. The storage units created for this purpose are called umbilical blood banks.
Bone Marrow (Stem Cell) Transplantation Process
Preparing the Recipient for Transplantation
A complete medical history is taken from the transplant patient, a physical examination is performed and all tests for organ function are performed. On the other hand, the patient is evaluated in terms of oral and dental health and necessary treatments are administered before transplantation. The patient's previous viral illnesses are also investigated and shown to be free of infection. A central venous catheter is then inserted, often in the chest area, for a venous route through which all blood products and medications can be given during the transplant.
Preparing the Donor for Transplantation
The donor is examined for health status, viral and previous illnesses. He/She is informed about how to harvest stem cells. At the appropriate time, stem cells are harvested from the bone marrow or peripheral blood.
Pre-transplantation Preparative Regimen
Preparative regimens are high-dose chemotherapy and/or radiotherapy treatments administered to patients in the 5–10-day period immediately prior to stem cell transplantation. Preparative regimens are selected depending on the type of disease, stem cell transplantation and donor type. Preparative regimens have three main purposes. These are:
1. Making room in the bone marrow for the donor's stem cells,
2. Suppressing the patient's immune system to prevent rejection of the donor's cells,
3. Removing the patient's original diseased/cancerous cells from the body.
Preparative regimens have many side effects. Information about your child's preparative regimen, including details and side effects, will be shared with you before the transplant.
Administering Stem Cell
After preparative treatment, the harvested stem cells are introduced into the recipient's bloodstream through a central venous catheter, just like giving blood. The stem cells find their way to the bone marrow and begin to patch. After this period, the recipient is administered full supportive treatment. Prophylaxis for infections, blood transfusions when necessary and immunosuppressants to prevent tissue rejection disease, especially in allogeneic transplants. Pre-transplant days are indicated by “minus”, transplant day 0 and post-transplant days by “plus”. These enable both the monitoring team and the patient and family to understand the stage of the treatment process, what risks are involved and when the patient can be discharged.
Patching of Stem Cells
When the donated stem cells settle in the recipient bone marrow and start producing blood, this is called patching. Depending on the type of transplant, the underlying disease and the stem cell source, it takes place between days +15 and +30. Patching may be delayed or absent in cases such as infection, medical interventions, low number of stem cells given.
Complications Following Stem Cell Transplantation
Complications seen in stem cell transplantation vary according to the patient's age, organ function, type and degree of underlying disease, stem cell source, tissue compatibility between the donor and recipient, and preparative regimen. Secondary to the preparative regimen, most organs and tissues in the body are adversely affected. The use of immunosuppressives may lead to the emergence of opportunistic infections. Complications are divided according to the time of occurrence. Complications that occur within the first 100 days after stem cell transplantation are called “early complications” and complications after 100 days are called “late complications”.
Early Complications
- Infections
- Tissue rejection disease (graft-versus-host disease)
- Hepatic sinusoidal obstruction syndrome
- Transplant-associated microangiopathy
- Idiopathic pneumonia syndrome
- Diffuse alveolar hemorrhage
- Engraftment syndrome
- Hemorrhagic cystitis
- Posterior transient encephalopathy syndrome
- Mucositis
Late Complications
- Immune system: Infections, autoimmune syndromes.
- Endocrine glands: Underfunctioning of hormonal organs such as hypothyroidism
- Musculo-skeletal system: Bone and muscle losses
- Liver: Picture of hepatitis, fibrosis, damage due to iron accumulation
- Lungs: Interstitial fibrosis, bronchiolitis obliterans, late pneumonia
- Eyes: Cataract, keratoconjunctivitis, dry eye
- Oral mucosa: Dry mouth
- Teeth: Dental caries
- Nervous System: Leukoencephalopathy, nervous damage,
- Growth and Development: Short stature
- Urinary bladder: Scarring after hemorrhagic cystitis
- Kidneys: Nephropathy, renal failure
- Secondary cancers