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Bone marrow transplantation

bone marrowBone marrow transplantation is a procedure which is used for treatment of both adults and children suffering from leukemia (blood cancer) and aplastic anemia, as well as from lymphomas (such as Hodgkin disease), plasma cell myeloma,seriousimmunity disorders.

Bone marrow is spongy tissue located in the breast, skull bones, femurs, ribs and backbone, and containingstem cells from which blood cells are produced. Blood consists of white blood cells – leukocytes, which protect the organism from infections, red blood cells – erythrocytes, which are oxygen carriers, and thrombocytes due to which blood coagulates.

When stem cells of bone marrow begin to function incorrectly, namely to produce superfluous quantity of defective or immature blood cells,there develops leukemia, and when bone marrow sharply reduces their production - it leads to aplastic anemia.

Defective or immature blood cells fill the bone marrow and blood vessels, force normal blood cells out of thebloodflow and can spread onto other tissues and organs. To destroy the ill blood and marrow cells large doses of chemotherapy and/or radiotheraphy are required. Such treatment damages not only defective, but healthy marrow cells as well.
In the course of bone marrow transplantation, illbrain marrow of the patient is destroyed and healthy marrow of the donor is entered into the patient’s blood channels. In the case of successful transplantation, the transplanted bone marrow migrates into the large bone cavities, catches on and starts to produce normal blood cells.

If bone marrow which was received from the identical twin is used, such transplantation is called syngeneic - or allogeneic, if marrow is received from a donor. In the case of allogeneic transplantation (i.e. not from the relative), the donor bone marrow injected in the patientmust correspond genetically to his/herown as much as possible. To determine the compatibility of the donor and the recipient special blood tests are made.

If the donor bone marrow insufficiently corresponds genetically to the recipient’s tissues, it can perceive its organism tissues as foreign material, and then it will attackand start to destroy it. This condition is known as the graft-versus-host disease (GVHD) and can be life-threatening for the patient. On the other hand, the immune system of the patient can destroy the transplanted marrow. It is called graft rejection.
In certain cases the patient can be a bonemarrow donor for his/her own self. It is called autologous transplantation and it is possible if the illness affecting brain marrow is in the remission stage or when the condition demanding treatment does not affect the bone marrow (for example, in the case of breast cancer, ovaries cancer, Hodgkin disease, non-Hodgkin lymphomasand brain tumors).

PREPARATION FOR TRANSPLANTATION

Successful transplantation is possible if the patient is healthy enough to have a possibility to undergo such serious procedure as bone marrow transplantation. Age,general physical condition, diagnosis and disease stage - all of this is taken into consideration when the decision is made as to whether the patient can undergo transplantation. Before the transplantation the patient undergoes many tests.

Examination of the condition of heart, lungs, kidneys and other vitals is also used for reception of information about their initial level – so that after the marrow transplantation it would be possible to compare and determine whether a certain function has improved. Preliminary tests are normally made outpatiently before hospitalization.

Trifles play an important role in the marrow transplantation process. They should be taken into account as they can significantly influence the transplantation results. Successful bone marrow transplantation demands the presence of a highly professional medical team - doctors, nurses, supporting personnel who have a good experience in this sphere and are ready to distinguish and react to possible problems and by-effects immediately.

That is why correct choice of a clinic for bone marrow transplantation is very important for achieving of a needed result. Clinics specializing in bone marrow transplantation, have a program which includes the provision of emotional and psychological support both to the patients and their family members, before, in the process and after the transplantation.

RECEPTION OF BONE MARROW FROM THE DONOR

RECEPTION OF BONE MARROW FROM THE DONORToday transplantation saves thousands of lives annually, but unfortunately almost 70 percent of those who need transplantation cannot have it made because of the impossibility to find a compatible donor.

There is only 35 % chance that the patient has a brother or a sister whose marrow will perfectly fit. If the patient has no relatives whose marrow is suitable for transplantation, a donor can be found in the international register of bone marrow donors, or transplantation of not completely compatible marrow can be made. Irrespective of whose marrow - the donor’s or the patient’s or the relative’s - is used for transplantation, the procedure of marrowcollection is made in the operative theater, usually under general anesthesia. It provides minimum risk and minimizes unpleasant sensations.

While the patient is under anesthesia, a special needle is entered into a cavity of leg femur or pelvis. The quantity of bone marrow needed for transplantation depends on the patient’s size and the concentration of marrow cells in the collected substance. Usually from 950 up to 2000 milliliters of the substance consisting of marrow and blood are taken. Although this quantity seems to be big, in fact it makes only approximately 2 % of the human bone marrow volume, and a healthy donor’s organism restores it within four weeks.

After the bone marrow collectingprocedure the donor may feel a certain discomfort in the punctured place – normally the pain is similar to what one feels after heavy falling on the ice, and can usually be eliminated with the help of anesthetizing tablets. The donor, as a rule, is discharged from the hospital next day and in the nearest days can return to his/her everyday activity.
In the case of autologous transplantation the collected marrow is frozen and stored at the temperature ranging from -80 to-196 degrees Celsius until the transplantation date. First it can be cleared to eliminate the remaining cancer cells which cannot be identified under the microscope.

In the case of autologous transplantation the bone marrow can be processed with the aim of extraction of T-lymphocytes to reduce the risk of the graft-versus-host disease. Then the bone marrow is transferred directly to the patient’s room for intravenous introduction.

MODE OF PREPARATION FOR TRANSPLANTATION

In the course of preparation a small flexible tubule named catheter is entered into a large vein usually around the patient’s neck. This catheter is required for introduction of medicines and blood products, for blood sampling in the course of treatment, and to avoidmaking of hundreds of punctures on the hand veins.

While in the marrow transplantation department, during several days the patient is exposed to chemotherapy and/or irradiation which destroys his/her own marrow and cancer cells and clears a space for a new marrow. It is called conditioning or preparatory mode. A dose of chemotherapy given to the patient during the preparation, is much bigger than the doses which are given to the patients who suffer from diseases which do notdemand bone marrow transplantation. Patients may feel weakness, nausea and irritability. To minimize unpleasant sensations in the majority of bone marrow transplantation centers the patients are given preparations against nausea.

BONE MARROW TRANSPLANTATION PROCEDURE

Bone marrow transplantation procedure is made after one - two days following chemotherapy and/or irradiation. Bone marrow is introduced intravenously, like blood transfusion. Transplantation is not a surgical procedure, therefore it is made in the patient’s room, not in the operative theater. During the bone marrow transplantation the patient is often checked – whether he/she has no temperature, fever, chest pains.

Bone marrow transplantation is physically, emotionally and mentally hard procedure, both for the patient and for his/her relatives. The patient needs and must receive all the possible help to cope with this. Imagine the signs of a heavy flu - nausea, vomiting, fever, diarrhea, extreme weakness. Now imagine what it is like when all these symptoms last not for several days, but for several weeks.

After the transplantation termination there beginlong days and weeks of waiting; during all this period the patient feels very sick and weak. Walking, long-time sitting in the bed, books reading, phone conversations, visits of friends and even TV watching demand from the patient more energy that he/she has. Complications which can develop after the bone marrow transplantation, such as infections, bleeding, rejection reactions, problems with liver, can cause additional discomfort. In addition, in the mouth there can appearaphthae which complicate eating and make the process of swallowing painful. However pains can be normally controlled by means of medications. Sometimes there appear temporary mental disorders which can frighten the patient and his/her close people, however it should be realized that these disorders are temporary.

BONE MARROW ACCEPTANCE

The first 2-4 weeks after the bone marrow transplantation are the most critical. Before the transplanted marrow migrates into big bone cavities, takes roots there and starts to produce normal blood cells, it is very sensitive to infections and has an expressed propensity to bleeding. Transfusion of thrombocytes helps to fight bleedings. After the allogeneic transplantationpatients also receive additional preparations which make it possible to prevent and control the graft-versus-host disease .To help prevent and fight the infection and to minimize the risk of the patient getting infected with viruses and bacteria,he/she is given a lot of antibiotics and many blood transfusions are made. The hospital visitors and personnel wash their hands with antiseptic soap and in certain cases put on protective whites, gloves and masks when entering the patient’s room. The patient also sticks to these rules - when leaving the room he/she must put on a mask, whites and gloves which are a barrier against bacteria and viruses, and informthe people around that he/she is susceptible to infection. It is forbidden to bring to the patient’s room fresh fruit, vegetables, plants and flower bunches because theycan often be a source of fungi and bacteria which are dangerous for the patient.

Blood tests must be made on a daily basis, in order to determine if the new marrow acceptance is going smoothly, and to estimate the condition of the organism functions. After the transplanted bone marrow is definitively accepted and starts to produce enough healthy erythrocytes, leukocytes and thrombocytes, the patient stage by stage ceases to be dependent on introduction of antibiotics, blood and thrombocyte transfusions which gradually become unnecessary. If there are no extra complications the patient is discharged from the hospital. In typical cases, after the bone marrow transplantation patients spend in the hospital from 4 up to 8 weeks.

HOW TO COPE WITH EMOTIONAL STRESS

In addition to physical discomfort connected with the bone marrow transplantation, there is also emotional and mental discomfort. Some patients think that psychological stress in this situation is even more difficult for them than physical discomfort.

Psychological and emotional stress is connected with several factors:

First, the patient who is subject to the bone marrow transplantation, is already traumatized by the fact that he/she suffers from the disease which is a threat for his/her life. Although transplantation gives him/her a hope for healing, the prospect to undergo a long, complicated medical procedure which does not guaranteesuccess, is not rejoicing.

Second, the patients who are to undergo the bone marrow transplantation, may feel lonely and isolated. Special measures aimed at protecting of patients from infection while their immune system is weak, may cause a sensation that they are isolated from the world and almost from all usual human contacts. This isolation is felt by the patient exactly when he/she badly needs physical contact and support from the family and friends.

The feeling of helplessness is another usual experience among the patients who have undergone the bone marrow transplantation, and this feeling causes anger or indignation.Many of them can hardly tolerate the sensation that their life completely depends on other people, and they feel awkward when they have to depend on other people’s help in daily hygienic procedures like washing or using toilet.

Rehabilitation period reminds of a roller coaster –one day the patient might feel much better, and during the following several days he/she might feel seriously ill again. Waiting for the blood tests to return to the trouble-free level and for the by-effects to disappear at last, increases the emotional trauma.

DISCHARGE FROM THE HOSPITAL

After the hospital discharge the patient continues the process of rehabilitation at home within another 2-4 months, and he/she cannot return to the working activity at least within half a year after the transplantation. To control the rehabilitation process the patient needs to frequently go to the hospital where medications are infused and in the case of need blood transfusions are made. Although the patient might feel well enough to leave the hospital, the process of his/her rehabilitation is still far from being over. During the first several weeks he/she still feels too weak to do anything but sleeping, sitting and taking short walks not far from home. Within six and more months from the date of transplantation, the patient’s leukocytes are often at too low level to provide sufficient protection against viruses and bacteria which can be found in habitual life – that is why contacts with the general public must be limited. For a person in the state of rehabilitation after the bone marrow transplantation, it is forbidden to visit cinemas, supermarkets, department stores etc. Such people must put on a protective mask when they leave the home.

LIFE AFTER MARROW TRANSPLANTATION

About a year may be needed for a new marrow to start to function like the patient’s own. Life after transplantation can be both joyfully exciting and disturbing. On the one hand, it is a fascinating sensation - again to feel alive after being so close to death, on the other hand the patient always feels anxious that the disease can return. Besides, usual innocent words or events can sometimes bring back hard reminiscences about the transplantation period, even long time after full recovery. A lot of time may be needed for the patient to cope with these difficulties, though the majority of patients think that their life quality has improved after the transplantation.

IS IT WORTHWHILE?

Yes! For the majority of patients expecting the bone marrow transplantation, an alternative is almost inevitable death.

Bone marrow transplantation

Although transplantation can be a painful period, the majority of those who has undergone it, think that the perspective of returning to normal healthy life afterwards is worth all the efforts.


Donor. Questions and answers:

Q: How can a donor of marrow or hematopoieticstem cells be found?

A: All people inherit a unique genotype from their parents. Naturally, first of all a potential donor is looked for among the patient’s close relatives.A probability that brothers or sisters can be donors for each other, is about 25 %. Overall, not more than 30 % of patients have a potential donoramong their relatives. If there is norelated potential donor, an unrelated donor is searched for. There is an international computerized database of potential non-relative donors, which contains the tissue matching data of about 6 million people from every corner of the globe. Upon receiving an inquiry about the donor search, the computer system informs about the presence of suitable potential donors. Then the medical institution which is responsible for the treatment, contacts the donor register, the database of which contains the data of a concrete person who had expressed preliminary readiness to become a donor. The administration of the register of donors independently contacts the donor, carries out the "activation" procedure as a result of which the donor is either found suitable for transplantation and agrees to it, or refuses - or is found unsuitable as a result of a careful medical examination. If one potential donor was not found suitable for the transplantation, another donor is searched for.

Q: According to what criteria it is determined if the donor is suitable or not?

A:Proteins named antigens are located on the surface of leukocytes and other tissues of the human body. There are special antigens called HLA-A, HLA-B and HLA-DR. Their coincidence in the donor and the recipient determines the success of transplantation of bone marrow or hematopoietic stem cells. Naturally, people belonging to the same race, having the same ethnic and national identity, have higher chances to be donors for each other.

Q: What are the chances that a potential non-relative donor will be found?

A: In many countries of the world big efforts are made both at the state level and at the level of public organizations, to increase the number of potential unrelated donors and to consider thus all racial and national groups. About 80 % of all patients have at least one potential donor at the stage of preliminary search. This percent constantly grows (in 1991 itwas 41 %). It is important to add that out of these 80 % not everyone can bea real donor, and for the remaining 20 % transplantation nevertheless can often be successfully made from the donor who is suitable not completely but partly.

Q: What happens if the donor is found?

A: If a preliminary search pointed to a certain person as a potential donor, they contact him/her using the contact information given at the stage of preliminary conclusion of the Donor service Agreement. A potential donor undergoes medical examination and passes special tests for the purpose of more detailed studying of his/her compatibility with the patient. Then the potential donor signs the Donor service Agreement. By this moment he/she must be absolutely sure about his/her decision - because the patient at this stage can already prepare for the transplantation and undergo corresponding procedures.

Q: Can a potential donor refuse from the donor service and what consequences will this entail?

A: As a volunteer, a potential donor is not bound by any obligations. Sometimes a potential donor suitable by all criteria, may decide not to become a real donor. There is a number of reasons to refuse from the donor service, including a disease, spending of time and efforts, fearing the complications risk or painfulness of procedures. The donor service imposes serious obligations on a person – as human life depends on the potential donor’s decision. The decision change in the last moment can lead to fatal consequences for the patient who is waiting for the donor marrow - the consequences of such decision are explained to potential donors repeatedly and from the very beginning. The majority of potential donors go to the mat, having considered all pros and cons and understandingthe importance of their decision not only for the patient, but for their own selves as well.

Q: Who can become a potential donor of hematopoietic stem cells?

A: Any person at the age from 18 to55 years who was never ill with hepatitis B or C, tuberculosis, malaria, AIDS, malignant diseases, mental disorders. A potential donor gives 5 ml. of blood from vein to make tissue typing and check everything except for the last mentioned point. As to mental health, no certificate from the out-patient psychiatric facility is required from the donor.

Q: Do I have to pay for the right to become a donor? Or on the contrary, I will be paid?

A: Neither one thing not the other. Anonymity, voluntariness and gratuitousness arewhat any donor movement is based on. These principles were taken as a basis for creation of the Register of hematopoietic stem cells donors. Although practically all registers try to encourage the donors who gave theirhematopoietic stem cells to the ill person and thus saved his/her life.

Q: Please tell about the procedure of taking of hematopoietic stem cells?

A: There are two variants. You donate either some marrow, or stem cells from the blood current. The choice as a rule depends on the donor, but in rare instances it is dictated by medical demands.
If the donor gives his/her marrow, the puncture of pelvic bones is made under anesthesia, and then with a help of a surgical needle a necessary quantity of marrow is obtained. The procedure takes about 30 minutes. The marrow of the donor is completely restored in several weeks. After such procedure the donor spends 1-2 days in a specialized hospital under the doctor’s supervision.
If the donor gives his/her peripheral blood cells, several days before the blood donation he/she needs to start taking a special preparation Filgrastim which forces stem cells to leave the bone marrow and enter blood. The matter is that stem cells are collected from the blood current during the process called apheresis, when blood from the vein on one hand passes through a special device for hematopoietic stem cells separation and comes back to the blood channel through the vein in the other hand. Certainly this procedure is made in sterile conditions. One has to spend 5-6 hours in a quite motionless state, but there is no need either for hospitalization or for anesthesia. It takes 7-10 days for the collected cells to get renewed.

Q: What is Filgrastim?

A: Filgrastim has now been used for 10 years with the aim of increasing of leukocytes (white blood cells) production to enable patients with weak immunity to fight the infection more effectively. It is similar to the substance naturally produced by human body. During the last several years it has been given to healthy donors before the bone marrow transplantation to increase the leukocytes quantity in the blood current.

Q: Is there any risk for the donor’s health?

A: Bone marrow donation is a surgical procedure bearing minimum risk. Serious complications are rare. They can be caused by individual reactions to anesthesia; there are cases of the infection occurrence, reactions to the surgical needle introduction. After the bone marrow is donated, the donor may feel painful sensations in the operated area during a certain time. The donor of hematopoietic stem cellsmay feel pain in the bones, muscles, nausea, sleeplessness and fatiguecaused bythe preparation taken before the operation. The most typical by-effects are headache and pain in the bones. These painful sensations disappear right after the stem cells collection. During the apheresis procedure some donors complain of noise in the ears which emerges because of the usage of anticoagulant necessary for prevention of blood coagulation. After the procedure, these effects are gradually.

Q: Can I become a donor only for my relatives or friends?

A: The database includes potential unrelated donors who want and are ready to help anyone. If you want to go throughthe typing procedure only to help a certain person, inform about your intention, and your data will not be included in the general donor base. In the process of blood sampling you can ask the doctors to provide you with a copy of the immunological typing results.

Q: Can my parents sign the donor service agreement for me and why only people who are older than 18 years can be donors?

A: According to the International standards the volunteers must be full age. It is a question of surgical operation, and the one who agrees to it, must do so after informing his/herself about all the necessary information. A parent or a guardian has no right to sign the donor service agreement, because unrelateddonorship is a voluntary procedure which gives no benefits to the donor. Life saving is not talked about either.

Q: Why I cannot become a donor if I am over 55?

A: The number of years is not the only indicator of physiological age, but there is a demand to be guided by age when a donor’s suitability is determined. With the age there appears a small increase of by-effects risk during anesthesia. Studies have shown that the patients who have received hematopoietic stem cellsof elderly donors, have slightly worst statistics of treatment. Age restrictions, thus, are aimed at the provision of both maximum safety for the donor, and the best possible treatment for the patient.