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Bone Marrow / Peripheral Stem Cell Transplanatation

Bone marrow /peripheral stem cell transplantation procedure is a treatment method used for the patients with cancer (leukemia and other cancer types), congenital or acquired hematologic diseases causing bone marrow insufficiency (blood diseases), immune deficiencies (immune system diseases) as well as some hereditary (familial diseases). There are some therapy methods which are still in use for some of those diseases. However; bone marrow/peripheral stem cell transplantation is recommended if success chance is low or there is no possibility to completely eliminate the disease with those therapy methods. A donor who is a sibling or relative of the patient with full-match or near total partially-match tissue group should be found to practice this therapy method (HLA fully-match Allogeneic transplantation from related donor). If the donor cannot be found, transplantation can be performed from non-related donor (Allogeneic transplantation from HLA full-match non-related donor) and sometimes from the patient him/herself (Autologous transplantation).

As stem cell transplantation has high risk, transplantation is decided after patients' chances to have successful outcomes and risks of therapy are evaluated. Treatment with classical chemotherapy methods is possible for some leukemia types. For those patients, transplantation procedure is performed only if treatment is unsuccessful. On the other hand, possibility of full recovery with chemotherapy is low in some leukemia types Transplantation procedure is carried out at an early phase for those patients, if there is an appropriate donor.

Stem cell transplantation can be performed in childhood period for diseases other than leukemia and cancers. For disorders of bone marrow which is the main location of blood cell production, for the patients with insufficient or impaired blood production (aplastic anemia, thalassemia, fanconi anemia, hemophagocytosis, sickle cell anemia etc.) and for immune system disorders (immune deficiency, Griscelli syndrome), conditions can recover with stem cell transplantation. Transplantation can be decided for those patients depending on course, severity of disease, donor-related features and risks of procedure. Other diseases for which stem cell transplantation can be useful are familial diseases with different courses listed under hereditary diseases that mostly develop during childhood. There is a large variety of hereditary diseases. Some of them have no benefit from bone marrow transplantation. Some of them have mild courses and do not require transplantation. In some of those diseases, course is very severe and life threatening and/or they show progressive course. Sometimes, those diseases lead to skeletal system (bone, cartilage, joint) disorders while they sometimes cause progressive nervous system symptoms (neurologic diseases). Generally, there is no medical treatment method for those diseases. Transplantation procedure performed before disease progresses can be helpful for some of those diseases. However, disease can progress in spite of the transplantation.

For stem cell transplantation, a donor which has tissue group fully-match or sometimes partially match with the patient's should be found. If donor candidate cannot be found, or in some cases related to type of disease, patient’s own bone marrow or blood cells can be used for transplantation. This procedure is called ‘Autologous Hematopoietic stem cell transplantation’. Very high doses of chemotherapy can be applied thanks to this practice and bone marrow deficiency is prevented by transplanting patient’s own stem cells following chemotherapy.

BONE MARROW / PERIPHERAL STEM CELL TRANSPLANATATION (HEMATOPOETIC STEM CELL TRANSPLANTATION)

PREPARATION-TREATMENT AND MONITORING PROCESSES:

PREPARATION: Prior to the transplantation procedure, patients have detailed medical scanning regarding problems that may affect the course of transplantation. Similarly, donors should have a medical scanning to ensure that problems which may occur during or after obtaining bone marrow and harvesting peripheral stem cells are prevented or minimized. Those examinations are necessary also to prevent or minimize the risk of problem/side effect related to donor. For this purpose, detailed blood work, evaluation of kidney, liver, heart, nervous system, respiratory functions, complete treatment of tooth decays, sinusitis and similar infections that may cause serious problems during transplantation period are necessary in transplantation preparation process. Apart from this examinations and evaluations, other tests can be performed if they are deemed necessary. Some blood tests are performed for donors to investigate whether they have any infection or another problem that may pose risk. Moreover, preparations are made by evaluating blood work, chest x-ray regarding cardiac problems to ensure that the planned procedure (harvesting bone marrow or peripheral stem cell) is performed without problem.

Stem cells can be harvested from the donor in two ways depending on age, body weight of donor, condition of vessels and type of recipient’s disease: In bone marrow transplantation, bone marrow cells are harvested from the donor under general anesthesia in operating theatre. Peripheral stem cell harvesting procedure does not require general anesthesia. A medication is administered to the donor to ensure that stem cells enter into blood from bone marrow. (Granulocyte colony stimulating factor G-CSF = Neupogen or Granocyte). This procedure does not require hospital stay and is completed within approximately 2 to 4 hours. This procedure is called apheresis.

Regardless of the way of harvesting, bone marrow or peripheral stem cells are transplanted to the patients via intravenous route. To ease the administration of medication, fluid, intravenous feeding and blood product via intravenous route and also supply of blood samples to be taken for laboratory examinations necessary to be performed almost every day, a tube namely catheter or central line should be placed. This procedure should be performed approximately one week before starting therapy for transplantation and it is carried out by pediatric surgery, anesthesiology or radiology team under general anesthesia. Sometimes, unwanted conditions such as obstruction, infection, blood clot may occur in catheter. However, a central venous catheter should necessarily be placed to your child/relative for transplantation procedure. Measures are taken to prevent catheter-related problems.

TREATMENT: When pre-transplantation evaluations are completed and venous catheter is placed, patients are transferred to BMT unit where special rooms with HEPA filter system are available to spend the periods of administration of drugs required for preparation period, transplantation and post-transplantation. Visiting in this period is restricted since patients are under high risk of infection.

Preparation regimen contains the medication therapy applied to make room for bone marrow and destruct bone marrow cells producing abnormal cells (chemotherapy) and sometimes it also contains radiotherapy. Some of the medications such as busulfan, cyclophospamide, etoposid, fludarabin, melfalan can be given as chemotherapy for 7-10 days before the transplantation in preparation regimen and sometimes chemotherapy is given with radiation therapy that is called total body irradiation.

Most of the preparation regimen drugs are administered via intravenous line while some of them are given via oral route. After preparation regimen is completed, the day when stem cells are transplanted (bone marrow, peripheral blood or cord blood) is deemed as day 0. The harvested cells are transplanted inside the vessel via the catheter placed prior to procedure. High-dose chemotherapy applied during the preparation regimen affects not only the bone marrow cells but also the normal cells. As a result, temporary or permanent -although rare- changes can develop. Since every child would respond the medication therapy in different ways, some of the children suffer from few side effects while the other may have serious side effects.

After patient’s bone marrow is destructed, fever, infection, intraoral wounds, diarrhea, bleeding, hair loss may develop secondary to severe decrease in blood counts or swellings in body, problems in liver, kidney, brain, heart, lung, gastrointestinal system and other organs may occur until new bone marrow cells are produced (generally 3-4 weeks). As bone marrow complies with patient’s body, many problems regress. However, some patients may experience severe and progressive disorders. Some patients may develop "graft versus host” disease (GVHD) which is one of the most critical side effects of bone marrow/peripheral blood stem cell transplantation.

SUPPORTING PROCEDURES:

Patients are closely monitored to prevent side effects of transplantation procedure and supporting procedures are performed to minimize the risk of infection and prevent drug side effects. The post-transplantation period until compliance of the new bone marrow is the most risky period for your child/relative due to transplantation-related problems. To prevent the infections, patients are transferred to a separate room with special filter system (HEPA filter) which helps to protect patient from germs and patients stay in this environment until cells of body that are fighting against infection arise. Body care and oral care are provided to prevent infections. Drugs preventing infections are given.

Patients should follow special nutrition principles to protect their digestive systems from microorganisms. Intravenous feeding is provided for children that cannot tolerate oral nutrition since nausea/loss of appetite as well as intraoral wounds will develop because of intensive medication use and for possible infections, hepatic diseases. After patients’ general statuses of health improve and they tolerate oral nutrition, intravenous feeding is discontinued.

Until the transplanted stem cell starts to make sufficient producing (engraftment), blood products (erythrocyte and platelet) should be administered and this has vital importance. Red blood cells called “erythrocyte suspension” and yellow-colored “platelet suspension” which prevent bleeding are frequently used. Moreover, administration of white blood cells can also be necessary for the patients with persisting high fever, serious infection; although rare.

If blood readings elevate and there is no need of erythrocyte and platelet transfusion, patient tolerates the sufficient oral nutrition and there is no problem like infection during the observation period, patients will be ready for discharge minimum 4-5 weeks after stem cell transplantation.

POST-DISCHARGE FOLLOW-UP:

Following discharge, patients present for control visits monthly for two years and less frequently -once in several months- in following years depending on the complications during transplantation period and their current treatments. Sometimes, intravenous therapies can be applied in outpatient clinics during follow-up. Patients with weak immune systems secondary to transplantation itself and medications used are under risk of certain infections for at least one year and they should have vaccination during this period. After patients’ immune systems start to recover, all vaccines are re-started. Because, medications used during bone marrow/peripheral stem cell transplantation destroy the patient’s immune system. Protection from the prior vaccines is lost. According to patient’s condition, generally, some vaccines are administered at the end of the first month and the rest of them are administered at the end of the second month after they are planned by our party. Patient’s siblings should not be given polio vaccine within two years after transplantation. This vaccine is given orally. Rather than oral vaccination, polio vaccine can be injected to patient's siblings. If patient’s siblings are given oral polio vaccine, they should be kept away from their sibling who has undergone bone marrow/peripheral stem cell transplantation for approximately 6 weeks. Patient can start going to school within 6 months or 1 year during transplantation period unless they have a serious problem and if their immune system starts to recover.

If bone marrow/peripheral stem cell transplantation is completed successfully, your child/relative can fully recover and have a healthy life. On the other hand, permanent effects of transplantation can also be experienced in long term. Some patients may suffer from short posture, cataract, difficulty learning, respiratory problems or problems related to other organs.

The most critical long-term effect of transplantation is on ovaries. Secondary to high-dose chemotherapy and/or radiation therapies used during preparation period before transplantation, testes and ovaries may be affected and infertility is commonly seen in those patients. Adolescent patients can have child in the future with in vitro fertilization by freezing sperm and egg.

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