Every year thousands of people, including many children, are diagnosed with haematological malignancies such as leukemia, lymphoma and other hereditary hematological disorders. Some of these patients may be treated with chemotherapy and/or radiotherapy without the need for any further treatment. For others, however, bone marrow transplantation using a graft from a relative or a volunteer donor is the only suitable treatment. Bone marrow transplantation is a serious and painful process that today has become a standard type of treatment. To date, this treatment has saved the life of tens of thousands of patients worldwide.
The bone marrow is housed inside the large bones. All the different cell type of the hematopoietic and immune systems evolve from the stem cells residing in the bone marrow: these are the leukocytes (white blood cells), the erythrocytes (red blood cells) and the thrombocytes (platelets).
The role of white blood cells is the defense against infections. Lymphocytes are a specialized class of leukocytes that recognize foreign invaders that enter our body (bacteria, viruses etc), and activate immune response against them ultimately resulting in their destruction. The red blood cells contain hemoglobin and act as an oxygen transporting system providing oxygen to all the organs of the body. Platelets help heal wounds and thereby prevent bleeding.
There are two types of Bone Marrow transplantation:
An autologous transplant is the type of transplant that uses the patient's own stem cells. These cells are collected prior to the chemotherapy/radiation and returned to the patient at a later stage. They are used to replace stem cells that have been damaged by high doses of chemotherapy.
An allogeneic transplant is a type of transplant in which stem cells are donated to the patient from another person, such as a brother, sister or parent of the patient or from a person who is not related to the patient (an unrelated volunteer donor). Stem cells may also be retrieved from umbilical cord blood, which is an alternative form of an allogeneic transplant from an unrelated volunteer donor.
During allergeneic transplantation there is not only transfer of a new hematopoietic system but also a new immune system to the patient. At the beginning this has the attributes of the donor, but in a few months it assimilates to the new body. This is called immunogenic tolerance. The lymphocytes of the new immune system can potentially recognize and destroy existing malignant cells. This is called Graft-Versus-Leukemia Reaction and helps avoid the relapse of the disease.
Each person cannot donate a bone marrow transplant to any other person because the surface of our blood and tissue cells contain proteins, the histocompatibility antigens (Human Leukocyte Antigens, HLA antigens), that have a different composition for each person. While in monozygote twins (identical twins) the histocompatibility antigens are absolutely the same, in all other people they differ. The major HLA-antigens are summarized in groups named A, B, C and DR. In each group there are over 100-300 different antigens, thus creating infinite combinations. For allogeneic transplantation the donor and the recipient (i.e. the patient) should have a matching combination of HLA-antigens.
After the typing of your HLA-antigens through a blood test, blood is taken from any siblings for HLA-typing. The possibility that one of your siblings matches your HLA-antigens, allowing them to donate a bone marrow transplant to you, is about 25%. The possibility of a match with another relative other than your siblings is 1-3%. If we do not find an HLA-matching sibling or relative, then a search for a volunteer donor from our local registry is commenced which then proceeds internationally through Bone Marrow Donors Worldwide (BMDW). The search at the international registries can take approximately 3 to 8 months (see donor search process).
As soon as an HLA-compatible donor is found, your doctors will be informed in order to schedule the transplantation. Our endeavor is to always find the best possible matching donor for you. HLA compatibility is necessary so that there is mutual tolerance between the foreign bone marrow graft of the donor and your own body, thus preventing a severe reaction known as "graft-versus-host (recipient)” (GvH). However, under certain circumstances, some minor differences in the HLA between the donor and the recipient (partial HLA-compatibility) can be accepted.
When a matching donor has been identified and a transplantation is due to take place, a few weeks before the scheduled donation, an initial medical examination of the donor takes place at the center where the graft will be collected.
Apart from the clinical examination, a series of blood tests are carried out such as a chest X-ray, an electrocardiogram and an ultrasound of the abdomen. Then, a detailed explanation of the stem cell collection procedure is given to the donor.
Preparatory therapy called “conditioning” (chemotherapy and / or radiation) is usually required prior to the transplantation, so as to firstly destroy all leukemic or cancer cells and secondly to create the right conditions so that the patient’s body can accept the new bone marrow (stem hematopoietic cells, HSC). The HSCs will be given after the preparatory therapy. For the success of the transplantation it is crucial to administer a sufficient number of stem cells. The main side effect of the preparatory therapy is the destruction of the bone marrow and thus the reduction of the three types of blood cells: the red and white blood cells and the platelets. This is called anemia, leucopenia and thrombocytopenia, respectively.
After the administration of the transplanted cells (cells of the bone marrow / blood stem cells) to the patient and the expansion of white blood cells a new immune system is created in the new bone marrow. Immune cells called lymphocytes contained in the transplant can recognize the patient’s tissues as foreign and react against them. This reaction is called graft - versus – host (GvH), and the disease associated with this reaction is called ’Graft-Versus-Host Disease’ (GvHD). This reaction is manifested as acute inflammation mainly on the skin, the liver and intestine. There are two forms of GvHD:
Acute GvHD, which occurs during the first 100 days after transplantation,
Chronic GvHD, which may occur during the first year after transplantation or even during the reduction of immunosuppressant drugs that the patient is receiving.
GvHD may appear as a minor side effect not posing severe difficulties to the patient; however it can affect various organs such as the eyes, joints or lungs and develop into a very severe clinical condition that can put the transplanted patient’s life in danger.
In order to avoid GvHD, immunosuppressive drugs are administered before, but mainly after the transplantation in an effort to suppress the graft-versus-host reaction. The risk of suffering GvHD is not the same in all cases. As already mentioned, the risk is greater with greater HLA disparity i.e. with a nonrelated donor as compared to an HLA-matching sibling donor. For this reason, choosing the best compatible donor (higher degree of HLA matching) is essential in allogeneic transplantation of blood stem cells.