What is bone marrow and what vital functions does it perform?
Bone marrow is one the most important parts of the body for hematopoiesis (the process of producing new blood cells as old ones die or denature). It is also involved in immunopoiesis (immune cell production). Bone marrow is the only tissue of an adult human which contains large numbers of immature, undifferentiated and low-differentiated cells known as stem cells, which are structurally similar to embryonic cells. The total bone marrow mass in the adult body is between 1.6 kg and 3.7 kg, with an average of around 2.6 kg.
The main functions of bone marrow are:
- formation and maintenance of immunobiological processes;
- bone formation;
- participation in the exchange of proteins, fats, carbohydrates and minerals;
- production of protein bodies, synthesis of cholesterol and ascorbic acid;
- participation in the metabolizing of iron;
- the formation and storage of blood (on average, the process of hematopoiesis takes between 3 and 7 days)
When there is a pathology of the bone marrow, this affects hemopoiesis (blood formation) and immunopoiesis (immune cell formation), and without necessary treatment, this can lead to irreversible functional abnormalities in organs, organ systems and in the bone marrow itself.
Hematopoietic stem cell transplantation (HSCT) is a method of treatment used in hematology and oncology for the treatment of diseases of the blood and bone marrow, as well as some other diseases. In daily life, the term 'bone marrow transplantation' is commonly used. Hematopoietic stem cells can be found for transplantation from a variety of sources, including from the bone marrow itself (BMT), from the blood (PSCT) or from blood from an umbilical cord.
There are three types of bone marrow transplantation:
- bone marrow transplantation (BMT);
- peripheral stem cell transplantation (PSCT);
- umbilical cord blood transplantation.
Depending on the source of the bone marrow cells two types of BMT are distinguished:
- allogeneic (AlloBMT) - in which a bone marrow from a relative or non-relative compatible donor is injected to the patient. As a variant of AlloBMT is a syngeneic BMT (transplantation from an identical twin).
- autologous (AutoBMT) - when the recipient receives his own pre-prepared bone marrow;
Indications for hematopoietic stem cell transplantation:
- Acute myeloblastic leukemia;
- Acute lymphoblastic leukemia;
- Non-Hodgkin's lymphoma;
- Hodgkin's lymphoma;
- Multiple myeloma;
- Myelodysplastic syndrome;
- Chronic myelogenous leukemia;
- Chronic lymphocytic leukemia;
- Bone marrow failure: aplastic anemia, Fanconi's anemia;
- Paroxysmal nocturnal hemoglobinuria;
- Primary amyloidosis;
- Testicular cancer, ovarian cancer / Ewing's sarcoma;
- Hereditary diseases: Hemoglobinopathies;
- Acquired Immunodeficiency Syndrome (HIV);
- Autoimmune diseases (scleroderma, lupus erythematosus, rheumatoid arthritis).
Contraindications to the hematopoietic stem cell transplantation:
- Period of gestation (relative);
- Different immune system disorders;
- Long-term therapy with hormonal drugs and antibiotics.
- Internal organs dysfunction (kidneys, liver, lungs, cardiovascular system);
- Active infection;
- Bad performance status (WHO index > I)
- Chemotherapy-resistant recurrence of solid tumor or oncohematological disease;
- Refractoriness to the platelets transfusions.
The most serious obstacle for transplantation process is the donor and patient incompatibility. As a rule, donor material is taken from the patient himself or from his relatives.
What does a hematopoietic stem cells transplantation procedure represent and what stages does it consist of?
Stage of donor selection
Bone marrow donor selection is a complex procedure that is performed on the basis of donor and recipient tissue compatibility. The compatibility of blood groups according to the AB0 system is herewith mandatory.
Relative donors are considered to be the compatible according to the HLA system recipient’s brothers or sisters (siblings), the probability of full compatibility with a brother or sister is 25-30%. Parents and children are haploidentical (they have one common chromosome from each pair, that is, the coincidence between them makes 50%) and cannot be donors of allogeneic bone marrow.
If there are no brothers and sisters suitable for donation, it is necessary to look for non-relative bone marrow donors, including as well from the international donor bank.
Preoperative stage and diagnostics
Before the hematopoietic stem cell transplantation, the recipient and the donor undergo an extensive examination in order to determine the tissues compatibility.
Obtaining bone marrow
Regardless of the fact whose bone marrow, the donor’s or the patient’s, is used for transplantation, the procedure of material obtaining is similar in both cases. Bone marrow obtaining is performed in the operating room, usually under general anesthesia. This process leads to minimal risk and minimizes sense of discomfort. While the patient is under anesthesia, a special needle is inserted into the cavity of the leg femoral bone or the ilium of the pelvis, where a large amount of bone marrow is usually found.
If the stem cells are obtained from the peripheral blood, the human is being put on a mechanism that collects his blood and divides it into fractions. Such a procedure is painless. After that the cells are transmitted to the laboratory where the most important preparation stage is carried out.
When the donor is found and his compatibility is confirmed, the patient undergoes the procedure of conditioning.
This procedure has two aims:
- destruction of own bone marrow, which produces abnormal hematopoietic cells;
- immune system suppression in order to reduce the risk of donor cells rejection.
The patient, who starts undergoing the procedure of conditioning, won’t survive without transplantation.
Bone marrow transplantation process:
- Conditioning (7-10 days): chemotherapy and / or radiation therapy in order to create a "place" for new healthy cells
- stem cell transfusion (within 1-2 hours): intravenous infusion through the central venous catheter
- prevention of infectious complications, the patient does not yet have (2-4 weeks) the immune system, therefore is in a sterile box, receives parenteral nutrition and antibacterial therapy
- engraftment (several weeks): treatment and prevention of a possible "graft-versus-host" reaction with the help of immunosuppressive agents
- post-transplantation period (from several months to several years): complete recovery of all the bone marrow functions, gradual withdrawal from immunosuppression state
- Infusion of allogeneic, defrosted autologous bone marrow or HST of peripheral blood is performed intravenously.
The most frequent and dangerous complication after bone marrow transplantation is the “graft-versus-host” reaction (GVHR). An acute GVHR can develop during the first 100 days after transplantation, a chronical one – at a later term. In the majority of cases immunosuppressive agents are used to prevent and treat GVHR.
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