Bone marrow transplantation, transplantation: in leukemia and anemia
The normal functioning of the bone marrow is constantly working to create new blood cells that enter the blood stream to replace the aged and dead in the performance of their main tasks to ensure the life and protect the body. The bone marrow is closely associated with the immune system, because it, along with other organs of the immune system actively participates in immunoplate.
Bone marrow transplant (KM) is frequently presented latest hope for treating many patients suffering from diseases of the hematopoietic system, which is not amenable to other methods of exposure. In addition, bone marrow transplantation can help in congenital and acquired abnormalities of the immune system, as well as the lesions caused by the harmful for the body doses of chemical and radioactive substances.
Interestingly, attempts to transplant stem cells were made in the 19th century, but they could not succeed because it was not opened leukocyte HLA system, particularly inside diversity (polymorphism) and to ensure the immunological compatibility of donor and recipient (first antigen of this system was discovered only in 1954 of the last century).
The leading role in transplantation owns located on a small area of the sixth chromosome to the main histocompatibility complex, which includes the loci of the above-mentioned system (HLA) and a variety of loci other systems. The main task of the genes of the major histocompatibility complex is the control of synthesis of tissue antigens.
Gives a chance for life
A deep clinical study of the major histocompatibility complex, in General, and HLA in particular, the combined efforts of many specialists in the field of Hematology, immunology, biochemistry and given the opportunity to consider a bone marrow transplant as one of the most important treatments for many malignant diseases of the blood, which before were considered incurable. The correct definition of evidence deemed essential to successful transplantation of tissues active (red) bone marrow (hematopoietic tissue) that can restore normal hematopoiesis in the patient (recipient).
However, the greatest effect of bone marrow transplantation can be expected, if there is oppression because of the inferiority of stem cells rather than the microenvironment KM. Bone marrow can save the patient’s life in cases of congenital and acquired pathological conditions of the hematopoietic and lymphoid system, which include:
- Aplastic anemia;
- Leukemia (acute and chronic);
- Serious immunodeficiency disease, inherited, where the primary severe mixed immunodeficiency is an absolute indication for surgery;
- Disease accumulation;
- The Fanconi Anemia;
- Most thalassemia;
- Children’s malignant osteoporosis;
- Malignant lymphoma;
- Solid neoplastic processes localized outside the bone marrow.
The first place among the pathological conditions in need of correction of hematopoiesis of donor bone marrow, divide the leukemias and aplastic anemia. Moreover, in leukemia donor bone marrow is not only to replace diseased organ, and will work instead, but will take on the role of immunostimulant capable of giving an adequate immune response to the tumor antigens of leukemia cells.
In aplastic anemia the main goal of transplantation of hematopoietic tissue aimed at restoring the functional abilities of one’s own KM. This category of patients has all the chances of recovery, provided a compatible transplant for antigenic determinants of the main complex.
In the case of immunodeficiency syndromes a very important factor is the identification of the causes of the disease: it may be a disorder of the functional capacities of the lymphoid system or the inferiority which giveth life to all elements of the blood stem cell.
It should be emphasized that more than 50% of patients requiring transplantation of donor hematopoietic tissue, are in childhood, because, as you know, the disease, which is colloquially called a «blood cancer» – young. Features transplantation in children is at doses of drugs (often) their names and, in other cases, the use of other equipment (they are not all suitable, so the cost of treatment may increase). All stages of the transplantation KM, including the preparation, the children are in the same sequence as in adults, so it makes little sense to speak of these matters separately.
New treatment – new challenges
However, it is not so simple. As it turned out, the final success depends on many factors, that is, the new, the most progressive and effective method of treatment of hematologic pathology, has brought new challenges, among which are:
In addition, despite the constant growth of direct KM, doctors, patients and their families are constantly faced with other problems:
- To choose the right donor is extremely difficult, because obviously only identical are identical twins;
- Preparation for transplantation requires special equipment and considerable financial costs.
- This operation and follow-up can be simply not affordable to the patient’s family, if the family is not going to be a person of the same HLA phenotype (HLA matching on the first and second class).
It should be noted that the grafting is able to give life to a new nutritious cells, involves not only a bone marrow transplant. Besides him, transplanted stem cells of peripheral blood (MSCC) and using cord blood, which itself is already a storehouse of stem cells.
Depending on the place of receipt of material talking about the transplantation of autologous (patient transplanted prepared gemopoeticescoe own tissue) and allogeneic, meaning the donor’s bone marrow.
For example, the lymphoma that started in the lymph nodes, in the course of its progression can spread to the bone marrow. To avoid this, the patient taking healthy tissue and sent to storage, and then transplanted to the patient. Such transplantation allows to expand the range of chemotherapeutic activities in the future, because it eliminates immunological reactions between host and graft (tissue own).
Transplantation of an allogeneic transplant require patients whose hematopoietic organ has virtually ceased to function properly and is no longer able to resume its work. Such people are the last hope for relatives or to those who willingly sacrifices his hematopoietic tissue to save another person.
Some potential donors plunges into shock the very name of future operations. They believe that giving such precious material, certainly suffer themselves. This is because many people do not know the principles of fence KM, and the consequences of the procedure «draw» in your mind. However, terrible for the body, giving AWAY nothing, excuse does not entail any serious consequences, if not to consider complexity of the procedure and the soreness in the fence material.
Voluntarily to offer their services and be entered in the register of potential bone marrow donors can every healthy person between 18 to 55 years, whose blood never got the viruses of hepatitis b and C, HIV and Mycobacterium tuberculosis who do not suffer mental disorders and does not have malignant cancer pathology. However, the person giving your bone marrow, you must understand what threatens the recipient’s concealment of these diseases, so often the study of antigenic characteristics of red blood cells exposed personnel donors who undergo regular medical examinations.
Video: information for bone marrow donor
How and where looking for a donor?
First in the queue for excusei typing for possible bone marrow transplantation with the aim of are close relatives of the patient. Due to the fact that the person receives (that is at his conception) half a set of genes controlling the synthesis of tissue antigens (haplotype) from each parent, the probability of a match with them on HLA-phenotype is not so high.
The ideal option is considered monozygotic (identical) twins, and good – brothers and sisters, that the laws of genetics, in 1 of 4 cases compatible set of antigenic phenotype of the recipient relative. Otherwise, the search begins among compatriots of the same nationality, which is quite a bit, so the chances of finding a suitable donor is low, or takes an appeal to the international registry, if for the upcoming operation has the necessary means.
To conduct a successful bone marrow transplantation may be subject to a high degree of antigenic compatibility between donor and recipient, and here we have to give special importance to individual factors.
Leukocyte HLA system
A special role in transplantation belongs to the leukocyte system (HLA), where tissue antigens presented in all its diversity on the blood cells – white blood cells (T — and b-lymphocytes). That is the HLA system determines, as the new owner will take other cells, what will be the duration of engraftment, and as the transplanted tissue will react to a new «place of residence» (if she didn’t like, followed by reaction «transplant against host»).
Given the polymorphism of the HLA system, not much hope that the same specific phenotype of the patient, the donor will be found quickly, it can be found among 30-40 thousand people. However, if you do not take into account «strong» antigens and cross-reactive, that donor can be found among 3 thousands of typed individuals, and if to raise the question of choice is not identical, and compatible donor, it can be found among the surveyed 130 people. However, the transplant-compatible relative to KM, the basic rate will have to do on immunosuppressive therapy after surgery, which helps to suppress unwanted reactions. In connection with the foregoing, to search for a donor is better among the tribesmen for the Asian, African, American phenotypes in the antigenic set may differ significantly from the European.
Other «influential» moments
Survival after transplantation some influence other antigenic system, in particular АВ0 and RH, therefore, in the case of a positive decision on the possible transplantation of KM from a specific donor to a specific recipient are individual samples for full compatibility. The incompatibility of these antigens in the presence of antibodies against A(II) B or(III) the patient («most inconsistent») or a donor («minor incompatibility») can result in hemolysis or reaction «transplant against host».
In terms of the upcoming bone marrow transplant can not be ignored the female sex, and patients receiving in the treatment of frequent blood transfusions. Women can be sensitized by prior pregnancies, childbirth and blood transfusions, and men enough, and blood transfusions, so this group of patients are suitable especially carefully and to find the antibodies (and in fact contra), not in a hurry to repot KM, otherwise the development of the phenomenon of secondary grafting and graft rejected «with terrible force» (sperotto).
It should be emphasized that the immune responses that are a major problem in transplantation, in its most severe form is typical for a bone marrow transplant, right here you need to keep in mind not only the degree of sensitivity of the recipient to specific proteins obtained foreign tissue, but the reaction of the tissue to antigenic set of the new owner.
A donor was found!
And here after long labors and trials (usually what happens when you search for the donor), suitable for HLA antigens was found. He agrees to excuse bone marrow and can not change its decision because of the patient beginning to prepare for the upcoming transplant (kill the bone marrow and the immune system of the patient, placed in a sterile chamber while waiting). Now the life of the patient depends entirely on the donor in the case of failure of the last excusei KM the patient is waiting for certain death.
Donor who agreed to give part of their blood-forming tissues, for one day put in the hospital, where under General anesthesia in the amount of ≈ 1 liter get precious material (through numerous punctures of the iliac bones). If bone-marrow tissue taken from the patient, i.e., autologous transplantation is planned, the material is frozen.
After the procedure the donor nothing bad is threatened, however, in places punctures the bone he can feel pain, which, however, easily treated with painkillers. Not worth much to grieve about the lost volume KM: in a healthy person it is restored within two weeks.
Preparing for stem cell transplant peripheral blood differs in terms of its withdrawal. Before the procedure the man who’s going to give skpk, helping her to move into the blood vessels, and to this end adopt special funds, called growth factors (sargramostim, filgrastim, etc.). Skpk is taken within 5 hours of apheresis.
Afereza system (special equipment) parts blood to pieces, takes the stem cells and the remaining blood elements back into the bloodstream of the donor. The performance of the device is ≈ 40 ml per hour and in 5 hours the donor gives about 200 ml of cells that could save lives.
Apheresis can be called absolutely safe procedure, even if it is carried out in children under one year of life. Yes, no need to wonder — the donor may be a child who turned six months, he is healthy and perfect in its phenotype (1 and class 2 HLA) a sick brother or sister. Usually bone marrow or stem cells taken from the baby when he will be 9 months if not there is an emergency and the material will not need before. Unfortunately, the statistics indicates that brothers and sisters in half of the cases (50%) are polyidentities coincides in the main antigens of locus 25% and the remaining 25% at the HLA-phenotype look like strangers.
By the way, to get a bone marrow transplant is possible and the person who has passed for 55 (60 years), but provided that the blood-forming tissue did not lose their functional abilities.
Before bone marrow transplantation – an in-depth examination of the patient with the purpose of studying the functional capacities of its organs and systems (the better they work, the higher the likelihood of a successful transplant).
The period of training is under constant supervision of doctors of the highest class. At the same time in this period is the preparation of immunological graft, which aims to achieve the following goals:
- Maximum reduction in antigenic activity of tissue structures of transplanted tissue;
- To suppress the functional activity of immunocompetent cells in the graft capable of developing a response against the tissues of the new host.
The difficulties of the immunological preparation of KM is that it should not disturb the hematopoietic and other functional capacities of transplanted tissue.
To transplant quickly adapt and catch on, it needs to get to comfortable conditions that are required to provide the recipient’s body. With this purpose, the patient undergoes this procedure, air-conditioning, which involves the use of aggressive chemotherapy drugs that destroy the bone marrow of the patient and weakens its immune activity. This procedure increases the degree of engraftment of foreign tissue, because in the future it (the fabric) will take on the tasks of life support of a patient’s body, which own bone marrow could no longer cope.
Stage of preparation for the transplantation occurs for the patient with limiting any contact, in conditions as close to sterile (house, food, linen, etc.). In this condition the patient is completely helpless (self-hematopoietic system is not working, the immune system is virtually nonexistent), so for a long time leave it without change is impossible.
Bone marrow transplantation, skpk or embryonic hematopoietic tissue is produced in the same sterile box. Operation works like a regular blood transfusion (introduction of fluid into a vein of the patient) and in no way similar to other surgical intervention.
After receiving the donor tissue begins a new, not less difficult stage. Success will depend on how you behave and the graft and the recipient’s body.
Life after bone marrow transplant
Engraftment of genetically alien tissue in a new body — the process is long (up to 2 months) and unpredictable. Life after a bone marrow transplant during the first weeks – another test for the patient, which takes place on the background of constant excitement and physical weakness. Nausea, diarrhea, fatigue, optimism is not added. Emotional stress is enhanced by the fact that cheer up the patient, only the nurses on duty, attends a sterile box, the other contact is prohibited.
At this stage, the patient is assigned a special drugs aimed at the prevention of unwanted complications. With the suppression of immunological reactions in humans decreases sharply anti-infective immunity, rather, it is non-existent. A weakened immune activity, helps to adapt foreign cells, but leaves fully without the protection of the patient’s body.
The first 1 – 2 months life after a bone marrow transplant, takes the hospital. And, even after leaving the facility upon discharge, the patient cannot be removed to a considerable distance (e.g. to go to another city). He should be able at any moment to go to the clinic to provide emergency assistance upon the slightest suspicion of complications.
After transplantation, the running AWAY, the patient can not even dream in the next 6 months to visit favorite team, exactly as to walk in public places or to go shopping, because at every step it will be in danger of meeting with the infection.
About a year the patient should be kept under the watchful eye of doctors, tests and examinations. Permission to feel the fullness of life the patient will receive only when doctors deem that the alien tissue safely «merged» with the patient’s body and started to perform all the functions of the lost bone marrow.
The survival of patients who are lucky enough in search and selection of foreign hematopoietic tissue, also depends on other circumstances:
- Age (win children and young people up to 30 years, and the children and all you can count on a full recovery);
- The nature of the course and duration of the disease prior to the procedure (it is advisable to get to 2 years old);
- Gender (women have a reaction of «graft versus host» develops less frequently).
Overall survival up to 6-8 years ranges from 40 to 80%. In the absence of reactions from the recipient and graft, that is, with good engraftment of the graft tissue patient from yesterday to start a new life, not limited to any particular age.
The majority of patients, according to their own responses, is happy with the change and can’t believe it’s already over. Meanwhile, the anxiety may not disappear for a long time, people always thinks that terrible disease will come back and then he has nothing to help… In such cases you should contact the therapist who will be able to instill faith in a brighter future without the disease.
The organization and cost
To date, world Bank data consists of 25 million typed by the HLA system of the donor. Among Western European countries the championship of europeís Germany, their register numbers about 7 million. In the former Soviet Union the leader of Belarus, as the most affected by the Chernobyl accident, Republic. There are already 3 years after the Chernobyl event was opened and actively worked tissue typing laboratory in Gomel and Mogilev. Currently, such laboratories are functioning in all regional centers, and the total number of potential donors of bone marrow is close to 30 thousand people. The larger the territory and population of Russia is significantly behind our little neighbor – the register is about 10 thousand people.
But clinics of the Russian Federation in its equipment does not concede to foreign institutions of a similar type. The doctors involved in the transplantation in Russia is justifiably proud of its clinics:
- Institute of children’s Hematology and Transplantology. R. M. Gorbacheva (St. Petersburg);
- The Russian children’s clinical hospital (Moscow);
- Haematological center of the Ministry of health of the Russian Federation (Moscow).
However, the main difficulties of transplantation KM in Russia — not so much the lack of the required number of specialized medical institutions, no matter how small the number of the register. The costs of the laboratories is quite impressive, government agencies in most to solve the problem is not in the state, the creation of a database and a search typed donors outside of Russia are not engaged.
It should be noted that the cost of the surgery is quite high in Moscow, for example, the smallest amount you can count on, is 1 million rubles, and in the Northern capital, and even more – about 2 million rubles. Transplantation abroad will cost a pretty penny: in the same Germany and the donor will select, and bone marrow transplantion, and post-operative treatment will do, but it will cost her 100 thousand euros. In Belarus, the cost of transplantation KM for adults, in principle, little different from that in Western Europe. Free operation you can count the units (on a budget, its own register is small).
However, children have some chances to get the donor bone marrow is free of charge or on preferential terms. There are contacts with Germany and the agreement with Belarus. Some part of the payment, may assume the Ministry, but to a greater extent one hopes to charities and volunteers willing to share their hematopoietic tissue disinterested.