Bone Marrow Transplant | Public Cord Blood Bank

What is Bone Marrow Transplant ?

Hematopoietic stem cell transplantation (HSCT) is an important medical treatment used in the last fifty years treating life-threatening illnesses like leukemia and other hematologic cancerous diseases, as well as severe aplastic anemia, disorders with failed bone marrow function, various genetic syndromes and inherited immune deficiency diseases.

At present, about 15,000 allogenic (donated by another person), hematopoietic stem cell transplants are performed annually, half of them in the United State., For  leukemia or lymphoma patients these transplantations is the last hope if earlier treatments, such as chemotherapy etc., has failed. Today, over 80% of all hemtopoeitic stem cells transplantations are performed for leukemia patients, and therefore most transplants refer to them.

Before the transplant, the patient's bone marrow is usually destroyed and their immune system suppressed, to allow for the transplanted stem cells to be accepted by the patient's body and not reject the transplanted cells. Similar to other cancerous diseases, also in leukemia cancer affected cells must be destroyed before injecting the healthy transplanted cells. This procedure is carried out by chemo or extensive radiation therapy. Bone marrow cells are the most sensitive cells because of their high deviding rate. The preparation stage prior to the transplantion, takes a few days, the patients must stay in isolation to prevent chances of infection when the immune system is suppressed.

The transplantation is done by IV injection, thus, the stem cells are introduced initially  to the blood flow. Eventually, the stem cells move to the bone marrow, repopulate this tissue and begin producing healthy new blood cells. It takes a few weeks until sufficient blood cells are produced from the transplanted cells and this can be followed by measuring certain leukocytes (white blood cells) or platelets in the patient's blood stream. In some instances the patient require additional transplants or other treatments to expedite the engraftment process.

Transplanted stem cells are expected to function where the previous ones failed: identifying and destroying the cancerous cells, even if cancerous cells remained in the patient's body, the transplanted cells and the new blood cells produced will fight and destroy those damaging cells. This process is called GVL – Graft Versus Leukemia and is essential to the recovery and survival of the patient in the years following the transplant. This process will probably not occur with autologous (self) transplantions in which the patient is transplanted with his own stem cells. 

There are 3 sources for hematopoetic stem cells transplantations:

1. Bone Marrow Harvest – Harvesting some of the donor's bone marrow cells which is performed under anesthesia (general or local) by inserting a long needle into one or more of the large bones (usually from the hip). Since the possibility to collect stem cells from peripheral blood has been assessed, this method is used less frequently due to side effects and resultant pain. It is mostly used when donating for a family member or harvesting from a child.
 

2. Peripheral blood stem cells are collected from the blood stream by a process known as apheresis. The donor's blood is withdrawn through a sterile needle in the arm, similar to a blood test. This procedure is obviously much less traumatic for the donor. To boost the peripheral stem cell production, repeated daily subcutaneous injections of cell growth factors such as granulocyte-colony stimulating factor are administered to the donor prior to the stem cells collection.  This yields higher stem cells mobilization from the donor's bone marrow into the peripheral circulation.  Peripheral blood stem cells are now the most common source of stem cells for allogeneic HSCT.
 

3. Cord blood is obtained from the placenta immediately after delivery and the diconnection of the baby from the umbilical cord. If not collected, the placenta and the blood within are otherwise disposed and thrown away. This blood is mostly donated by the infant's mother .  Cord blood can be donated to a public cord blood bank where it is being processed, checked and stored in -1960C (in liquid nitrogen). Public cord blood banks store the cord blood units for any needing patient worldwide for decades. Cord blood is used at present as an important alternative to the other 2 procedures mentioned above, and naturally also here require a satisfactory degree of tissue matching between the patient and the donated stem cells. Although cord blood contain a high proportion of stem cells , but due to the fact that the stem cells content here is not always sufficient for an adult patient and thus was used in the past only for young children, newer techniques enable today to obtain much higher cells content when compared to the past. Furthermore, at present  a new technique using two cord blood units from different donors has been developed with very promising successes in order to shorten the transplantation process and to allow cord blood transplants to be used also for adults and not only children.

In all instances, the HSCT is done to rehabilitate and build the bone marrow in the patient. The main factor for successful HSCT is the level of matching of the tissue type of the patient and the transplanted cells. The HLA – Human Leukocyte Antigens, located on the 6th chromosome, encodes antigen-presenting proteins that are present in the outer cell membrane. It identifies cells as either "self" or "foreign" and stimulates the immune system to protect against foreign cells. 

In some cases and diseases, autologous (self) bone marrow transplants can be performed.  In such transplants, healthy, unaffected stem cells of the patient are collected.  After radiation or chemotherapy, those stem cells are frozen for future use when they will be transplanted back into the patient from whom they were collected. Obviously such transplants are fully matched.

Nevertheless, in most cases, autologous transplants are not practical because the bone marrow is considered to be affected with cancerous cells or contain the defective gene in cases of inherited disorders. It is then necessary to obtain blood cells for the transplant from a donor. The best source in this case would be a family member, in most cases a sibling, who have a 25% probability of being fully matched. In the case that no matching family member is found, the search is conducted, mostly through an international registry organization that store the information of tissue typing charecteristics from banks from all over the world. The center is called BMDW, it is an international registry located in Leiden, Holland.

The registry has millions of potential donors, including over 200000 cord blood units.  The registry gathers the details from bone marrow banks around the world, as well as hundreds of thousands of cord blood units stored in public blood banks. A computerized search is done with the tissue type of the patient and other parameters by the transplantation center.

When the doctor decides that the transplant will be done from cord blood, a request is made to the cord blood bank for a certain unit that was identified to be suitable for a specific patient. After details of a cord blood unit are provided, the unit is sent to the transplantation center in a special container which maintains the viability of the cells by deep freeze at -196°C. Today, successful cord blood transplantations are successfully performed even without a full match of tissue type between the unit and the patient. This is another important advantage of cord blood

After the transplantation, the patient remains in isolation under strict supervision as the bone marrow is not yet functional and the blood count is down. The isolation continues until acceptance of the transplant, and the production of new blood cells. Exposing the patient to infection during isolation can be fatal. In addition, the recipient gets infusions of platelets and sometimes red blood cells until the engraftment is complete. A successful engraftment is manifested by rising blood count and other symptoms.

Even after engraftment and a stabilized blood count, the recipient is still in danger of infection and diseases for many months until the immune system is rehabilitated.

Another common problem in bone marrow transplants is GVHD – Graft Versus Host Disease, where the transplant which is part of the immune system of the donor, turns on and identifies the patient's body cells as foreign and attacks them, recognizing it as "a foreign object". GVHD involves many of the body's tissues and organs (such as skin, digestive system, liver, blood and lymph nodes etc.) and is a crucial factor in the survival of the recipient. Most recipients receive additional medications to suppress the immune system so as to alleviate this danger. It should be noted that cord blood transplantions, including double units are mostly involved with less severe GVHD than bone marrow of peripheral blood cells.

Recently, new methods have been developed to treat this phenomenon, among them the neutralization of T lymphocytes (responsible for the immune response to GVHD and GVL) before the transplant. Another method is the "mini transplant", where the preparation stage is less aggressive and the length of time the recipient's immune system is suppressed can be reduced. In this sort of transplant it is expected that the transplanted cells will successfully attack the cancerous cells, but at the same time, more aggressive suppression of the immune system is necessary in order to prevent rejection of the transplant.

It is worthy to note, that over 20000 cord blood transplants were performed internationally, and the success rate of cord blood treatments were found to be similar to those of bone marrow or peripheral blood transplants.  However, since then studies and research prove that cord blood transplants show even greater successes. This is in addition to the latent benefits in public cord blood banks as a source for treating various other diseases.

Cord blood banks has another very important advantage. These banks store cord blood units from very many different ethnic backgrounds. This is an important issue, since many minorities, including various Jewish ethnic groups found it extremely difficult to find a suitable (matching) donors due to the exclusive unique genetic background.