Bone marrow transplantation

It is the administration procedure of transplanting the bone marrow which is collected from a healthy person to the patient with blood/bone marrow diseases, cancer or congenital diseases, through intravascularintravascular. For the bone marrow to be matched, the marrow and blood cells of the patient should be removed. Thus, blood cells and bone marrows of patients are destroyed by giving very high doses of cancer medications (chemotherapy), even if the patients do not have cancer. This procedure generally takes 7 to 10 days. At the end of this period, bone marrow of the patient becomes non-operative and construction of blood cells stops. It takes approximately 15-20 days for the new marrow to establish itself. Until the bone marrow establishes itself, infection/fever, mouth sores, diarrhea, bleeding and hair loss occur due to decreased resistance against microbes, as blood cells are not constructed. In addition, other adverse effects (hepatic, nephritic, cardiac and other organs) may occur due to high doses of medications. In order to prevent these adverse effects, patients are transfused blood, blood products (platelets, plasmas) and preventive medications. Patients are observed in hygienic and hepa filtered rooms if possible, special diets are prepared carefully for proper nutrition. Sores are tried to be prevented with continuous oral care. However, oral nutrition becomes difficult, as a result of mouth sores, loss of appetite and decreased sense of taste which occur in most of the patients. In this period, most patients may be supported with drip-feed. Within 15-20 days after the marrow establish itself, fever reduces and the mouth sores are recovered. Patient becomes to be discharged from hospital, 1 month later the marrow transplantation. However serious adverse effects can be observed in particular patients; 10-30% of patients can be lost within the first 3 months, due to the serious adverse effects. Discharged patients are continued to take particular oral medications and they are transfused medication once a month. Generally all medications are terminated within 6 months. And they may return to school in 6-8 months normally. As heavy medications administered to patients of bone marrow transplantation cause loss of effectiveness of pre-administered vaccines, it is required to resume vaccines within 9-12 months.

- What are the long-term adverse effects of bone marrow transplantation?

Slowdown in development / short stature, disorders of thyroid gland, osteoporosis, delays/problems in puberty development, cataract formation may occur due to high doses of chemotherapy and lower doses of radiotherapy. The treatments and preventions of these diseases may be possible with watchful waiting. Infertility may be observed, when patients become adults. Transplanted patients have more risk of developing a type of cancer (for instance, on skin) when compared to healthy individuals, but this risk is not high.

- What is stem cell? May blood or umbilical cord blood be used as stem cell source, instead of bone marrow?
Stem cell is the main cell that is in bone marrow and it helps the marrow to establish itself and to construct healthy bone marrow and blood cells. In fact, the term "stem cell transplantation" is generally used instead of "bone marrow transplantation" "Stem cell transplantation" means bone marrow, blood stem cell or umbilical cord blood transplantations. One of these can be used. Bone marrow transplantation is the most common one for children; however the transplantations of blood stem cell and umbilical cord blood have been spreading.

In normal conditions, there are very few stem cells in the blood. After applying an injection (vaccine) called growth factor to the donor for 4-5 days, stem cells pass to blood from bone marrow and stem cell collection with apheresis instrument can be used instead of bone marrow transplant. Apheresis device is an instrument that is used to obtain certain blood products in blood bank. The blood vessels in both arms of the donor are entered in and connected to the device and the procedure is completed in a few hours. The donor is not required to be hospitalized. It has almost no damage for the donor.

Umbilical cord blood is normally a product, which is removed after birth. Cord blood has stem cells as the bone marrow. Therefore, the cord blood can be collected during birth and can be frozen in order to be used instead of marrow transplantation when needed. If a patient has a bone marrow transplantation requiring disease and if the mother is pregnant, it will be appropriate to collect and preserve cord blood of the sibling to be born. The collected cord blood can be used instead of morrow transplantation even if it matches with the tissue types of the patient partially.

- For which diseases is bone marrow transplant applied in children?

Diseases related with blood or bone marrow
Inherited immunodeficiencies (immune system deficiency)
Inherited metabolism diseases
Other cancers (certain brain tumors and other childhood tumors)

- Who is the most appropriate donor for bone marrow transplantation?

Tissue types of the donor and patient must match for bone marrow transplantation to be practiced. Most appropriate donor is the sibling whose tissue type matches. Tissue type of the patient and father or mother has haploid matching. Fully matching can be seen rarely. If there is not a tissue-matching sibling or another family member, testing all relatives is normally useless. The possibility of finding an appropriate donor among other relatives is very low. When a full matching family member cannot be found, it is so risky to transplant marrow (or stem cells) from a non-matching person. Chance of success is really low. However, it can be successful in patients with congenital immune deficiency.

- What is tissue type compatibility? How is it tested?

Definition of tissue types is performed in order to the most compatible donor for the patient. Blood is taken for this reason. Tissue types are the particular signs on leukocytes (white blood cells) in blood. These are called HLA-tissue types. Tissue types are different from the blood groups. Blood groups are the signs of erythrocytes (red blood cells). Compatibility of blood groups is not stipulated for tissue type matching. If tissue types of the donor and the patient match, transplantation can be performed even if the blood groups are different. However, it is preferable for the blood groups to be the same. Blood is taken from the patient, siblings and mother and father, if alive, for tissue type definition. Collection of bone marrow is not required for tissue type definition.

- How is bone marrow collected from the donor? Is it harmful to the donor?

If there is a matching sibling in the family, she/he is tested whether she/he is appropriate for transplantation. Blood tests/ certain simple laboratory tests are performed. Collection of bone marrow from the donor is practiced under anesthesia. Marrow is collected by needles into syringes from the hipbone of the donor. The collected amount varies according to the weight of patient. Marrow collection procedure has almost no damage for the donor. Very few adverse effects of this procedure have been reported. The collection is performed under surgery conditions. Slight anemia can be seen in the donor. The donor returns to normal with the help of oral iron pills. Giving blood is not required. The donor can return to work or school within 3-5 days.

- What should be done unless suitable donor is found in the family?

If there is not a suitable donor in the family, the bone marrow or cord blood banks can be searched. However, finding a full-matching (6/6 HLA matched) donor is not always possible. There is not a bank in real terms, particularly in Turkey. There are a few centers which have still being developed. It is difficult to find a suitable donor for a Turkish patient from the banks in abroad. When it is found, the transportation of the marrow or cord blood to Turkey can be possible under certain circumstances. Nevertheless, there are several risks in transplantations from foreigners and the chance for success is low. A number of centers have been dealing with creating a bank in Turkey due to difficulties and risks of providing marrow or cord blood from abroad for patients in Turkey. However, a comprehensive and real bank has not been established yet. Tissue types of 7-8 million volunteers have been identified in various banks across the world. If tissue of a donor matches with a patient’s, the date is determined for the collection of bone marrow by contacting the donor. It is easier to obtain the cord blood, when found. Because cord blood is preserved in the bank as collected, frozen and tested. It is easy to reach the product when needed. However, adequate amount may not be obtained as the amount of cord blood is (particularly in overweight patients).

- What is autologous bone marrow (or stem cell) transplantation? For which diseases it is practiced? How many years can the frozen stem cells be preserved?
Autologous marrow transplantation may be preferred first for childhood tumors or if a suitable donor is not found. Autologous transplantation is the procedure of intravascular transfusing the patient's own bone marrow, after being exposed to high doses of chemotherapy. For tumors and certain types of leukemia, after the patient is administered chemotherapy and a large part of cancer cells are destroyed (after the marrow is cleansed partially), marrow is collected and stored in liquid nitrogen tanks at -180°C. The stem cells maintain viability more than 10 years, when stored under these conditions. Then the patient is applied high doses of chemotherapy/ radiotherapy. Almost all cancer cells are tried to be destroyed. Bone marrow of the patient becomes completely non-operative. Blood cells cannot be produced. Blood formation is obtained by applying defrosted marrow. In autologous transplantation, the risk of recurrence of the disease is higher, since the patient's own marrow is re-transfused. However, the adverse effects and treatment-related death rate is lower.