Bone Marrow Transplantation Unit

Bone marrow/peripheral stem cell transplantation is a treatment method applied in cancer (leukemia and other cancers), congenital or acquired hematological diseases (blood diseases) that cause bone marrow failure, immune deficiencies (immune system diseases), and also some hereditary (familial) diseases. There are still some treatment methods used for some of these diseases. However, if the chance of success with these treatment methods is low, or if there is no chance of complete recovery of the disease, bone marrow/peripheral stem cell transplantation is recommended. In order to apply this treatment method, the patient must have a sibling who is a complete or nearly complete match to the patient's tissue group or another donor candidate from the family (Allogeneic transplant from an HLA-compatible family donor). If not found, transplantation can be performed from non-relative donors (Allogeneic transplant from an HLA-compatible non-relative donor), or sometimes from the patient himself (Autologous transplant).

Since stem cell transplantation is a high-risk procedure, the decision to transplant is made after evaluating the chances of success and the risks of the treatment. Some types of leukemia can be treated with classical chemotherapy methods. In such patients, transplantation is only performed if treatment failure is observed. In some leukemias, depending on the type of the disease, the chance of complete recovery with chemotherapy is low. In these patients, if there is a suitable donor, transplantation is performed at an early stage.

In childhood, stem cell transplantation can be performed in diseases other than leukemias and cancers. There is a chance of recovery with stem cell transplantation in diseases with inadequate or defective blood production in bone marrow disorders (aplastic anemia, thalassemia, Fanconi anemia, hemophagocytosis, sickle cell anemia), immune system diseases (immunodeficiency, Griscelli). In these patients, the transplantation decision can be made according to the course of the disease, severity, donor characteristics, and also by evaluating the risks of the procedure. Other diseases that may benefit from stem cell transplantation are hereditary diseases, which are familial diseases that occur in childhood and have a different course. Hereditary diseases are very diverse. In some of them, there is no benefit from a marrow transplant. Some have a mild course and do not require transplantation. In others, the disease is very severe, life-threatening and/or progressive. Sometimes these diseases cause disorders of the skeletal system (bone, cartilage, joint) and sometimes progressive nervous system symptoms (neurological disease). There is usually no medical treatment for these diseases. In some of these diseases, transplantation can be beneficial if it is performed before the disease progresses. However, sometimes the disease may continue to progress despite transplantation.

For stem cell transplantation, it is necessary to find a donor whose tissue group is fully compatible with the patient, and sometimes partially compatible. In the absence of a suitable donor candidate, sometimes the transplant can be performed using the patient's own marrow or blood stem cells due to the type of disease. This is called 'autologous hematopoietic stem cell transplantation'. Thanks to this application, it is possible to give very high doses of chemotherapy to the patient, and the patient's own stem cells are given to the patient after chemotherapy, preventing the patient from entering bone marrow failure.

BONE MARROW/PERIPHERAL STEM CELL TRANSPLANTATION (HEMATOPOIETIC STEM CELL TRANSPLANTATION)

PREPARATION-TREATMENT AND FOLLOW-UP PROCESSES:

PREPARATION: Before transplantation, patients undergo extensive medical screening for problems that may affect the course of the transplantation. Similarly, donors should also undergo medical screening to prevent or minimize problems that may develop during and after bone marrow harvesting or peripheral stem cell collection. These examinations are also necessary to prevent or minimize the risk of donor-induced problems/side effects that may occur in the patient. For this purpose, patients should undergo detailed blood tests during the preparation period for transplantation, kidney, liver, heart, nervous system and respiratory functions should be evaluated, and infections such as carious teeth and sinusitis that may cause serious problems during the transplantation period should be fully treated. In addition to these examinations and evaluations, other tests may be performed if deemed necessary. Some blood tests are also performed on donors to check whether they have any infections or other problems that may pose a risk to the patient. They are also evaluated in terms of blood tests, chest X-rays and heart and preparations are made to ensure that the procedure (marrow harvesting or stem cell harvesting from peripheral blood) goes smoothly.

Stem cell harvesting from the donor can be done in two ways depending on the age, body weight, vascular condition of the donor and the type of disease in the recipient: In bone marrow transplantation, marrow cells are collected from the donor under general anesthesia (narcosis) in the operating room. Stem cell collection from peripheral blood is a procedure performed without general anesthesia (narcosis). Prior to this procedure, the donor is given medication (Granulocyte Colony Stimulating Factor G-CSF=Neupogen or Granocyte) in order for stem cells from the bone marrow to be released into the blood. This procedure, which does not require the donor to be hospitalized, is completed in approximately 2-4 hours. This process is called apheresis.

Regardless of the method of collection, marrow or peripheral stem cells are administered to patients intravenously. During the transplantation period, an intravenous tube called a catheter or central line must be inserted to facilitate intravenous administration of drugs, fluids, intravenous nutrition and blood products, as well as to facilitate the collection of blood samples for laboratory examinations that will need to be performed approximately every day. This procedure, which should be performed about a week before the start of treatment for transplantation, is performed under general anesthesia by the pediatric surgery, anesthesia or radiology team. The inserted catheter may sometimes develop undesirable conditions such as blockage, infection or clots. However, your child/relative must have a central venous catheter in order for the transplant to be performed. Measures are taken to prevent catheter-related problems.

TREATMENT: When the pre-transplant evaluations are completed and following venous catheter insertion, patients are taken to the BMT unit where special rooms with HEPA filter systems are available to administer medications as per the preparation regimen and to spend the transplantation and post-transplantation periods. Visits to patients are restricted during this period as they are at great risk of infection.

The preparation regimen includes drug treatment (chemotherapy) and sometimes radiotherapy to make room for the bone marrow and to destroy faulty bone marrow cells. In the preparation regimen, which is applied for 7-10 days before transplantation, some of the drugs such as busulfan, cyclophosphamide, etoposide, fludarabine, melphalan as chemotherapy, sometimes together with radiotherapy called total body irradiation.

chemotherapy may be given. Preparation regimen drugs are usually given intravenously, but some are given orally. After the preparation regimen is finished, the day on which stem cells (bone marrow, peripheral blood or cord blood) are collected is called day 0. The collected cells are injected into the vein through a catheter previously inserted into the patient. The high-dose chemotherapy administered in the priming regimen affects normal cells as well as bone marrow cells, which may result in temporary or, rarely, permanent unwanted changes. Since each child responds differently to the medication, some children may experience very few side effects, while others may experience serious side effects. 

As a result of the destruction of the patient's marrow, fever, infection, mouth sores, diarrhea, bleeding, hair loss, swelling in the body, problems in the liver, kidney, brain, heart, lung, gastrointestinal system and other organs may occur due to serious decreases in blood values during the period (usually 3-4 weeks) until new marrow cells are grown. Many problems improve with marrow retention; however, some patients may have serious and progressive disorders. Some patients may develop graft versus host disease (GVHD), one of the most important side effects of marrow/peripheral blood stem cell transplantation.

SUPPORTIVE PRACTICES: 

In order to prevent the side effects of transplantation, patients are closely monitored during the transplantation period and supportive practices are applied to minimize the risk of infection and prevent the side effects of medications. The time after transplantation until the new marrow takes hold is the most risky period for your child/relative due to transplant-related problems. To prevent infections, patients are taken to a separate room with a special filter system (HEPA filter) that protects them from germs and kept in this environment until the body's infection-fighting cells emerge. To prevent infections, patients receive body care and oral care. Anti-infection medications are given.

Patients have to follow special nutrition principles to protect their digestive systems as well as their bodies from microorganisms. Intravenous nutrition is administered to children who cannot be fed orally because of nausea/loss of appetite, the development of sores in the mouth and possible infections and liver diseases due to intensive drug use. Intravenous feeding is discontinued after the general condition of the patients improves and they can be fed orally.

Blood products (erythrocytes and platelets) need to be administered until the stem cell starts to produce enough (engraftment) and this is of vital importance. Red blood cells called "erythrocyte suspensions" and yellow colored "platelet suspensions" that prevent bleeding are frequently used in patients. In rare cases, white blood cells may also need to be administered in patients with persistent high fever and serious infections.

In the follow-up of the patient, the patient is ready for discharge at the earliest 4-5 weeks after stem cell administration, provided that the patient's blood values do not increase and there is no need for erythrocyte or platelet transfusion, the patient can be fed adequately orally and there are no other problems such as infection.

POST-DISCHARGE FOLLOW-UP:

After discharge from the hospital, patients come for follow-up visits approximately once a month for the first year and less frequently every few months in the following years, depending on the complications that developed during the transplant period and the treatments they are receiving. Sometimes, intravenous treatments can be administered in the outpatient clinic. Patients with a weak immune system due to the transplantation itself and the drugs administered are at risk for certain infections for at least one year and should not be vaccinated during this period. After the immune system of the patients starts to recover, all vaccinations are restarted. This is because the drugs used during bone marrow/peripheral stem cell transplantation have eliminated the patient's immune system. The protection of previous vaccines has been lost. Depending on the patient's condition, some vaccines are usually administered at the end of the first year and other vaccines at the end of the second year. Live polio vaccine should not be given to the patient's siblings in the first two years after transplantation. This vaccine is given orally. There is no harm in giving the polio vaccine, which is given by injection instead of oral vaccine, to siblings. If the patient's sibling has received oral live polio vaccine, he/she should be kept away from his/her sibling who has undergone bone marrow/peripheral stem cell transplantation for about 6 weeks. In the post-transplant period, patients can start school within 6 months or 1 year if they do not have any serious problems and their immune system has started to recover.

If the bone marrow/peripheral stem cell transplantation is successful, your child/relative's disease can be completely cured and he/she can have a healthy life. However, sometimes permanent effects of transplantation can be seen in the long term. Some patients may experience short stature, cataracts in the eye, learning difficulties, respiratory and other organ problems. The most important long-term effect of transplantation is on the ovaries. Ovaries (testes and ovaries) may be affected due to high doses of chemotherapy and/or radiation treatments used in the preparation phase before transplantation and there is a risk of infertility in these patients. In adolescent patients, sperm and ovaries can be frozen and they can have a child in the future through in vitro fertilization.