Stem cell transplantation is one of the great achievements of modern medicine. It is still under extensive research for most organs, especially for spinal cord surgery after transection of the spinal cord. On the other hand, the most advanced type of stem cell transplantation as of now is that of the bone marrow.
What is the bone marrow?
The bone marrow is the tissue located within the cavity of bones especially long bone like your thighs and arm bones and the axial skeleton including your hip bone and ribs. The bone marrow is a collection of cells and blood vessels with some bony trabeculations supporting the cavity. The main function of the bone marrow is the production of blood elements including red blood corpuscles, white blood cells and platelets. It may also function as the site of destruction of cells albeit in a much lesser extent than the spleen.
When we are born, most of our bone marrow is of the active or “red” type, which means that all of it produces cells actively, but as we grow older, most of that red marrow is replaced by inactive or “yellow” marrow. It is called yellow because of its high fat component. By adulthood, the active marrow becomes limited to the axial skeleton and some long bones like the femur (thigh bone). This is, however, reversible and in some cases when blood loss or red cell destruction is evident, the active marrow can expand to reach similar levels to those found in the newborn. This proves how adaptive and “plastic” our bone marrow is.
What is stem cell transplantation?
Organ transplantation in general often means removing an organ and implanting it somewhere else where it can thrive and not die. This process can occur within the same body, between different bodies of the same species or even between some members of different species. In humans, only the first two types are done within the clinical practice -although tissues from animals may be used in limited procedures especially in heart surgery.
The blood is a tissue, and a blood donation is a form of tissue transplantation, but blood cells have limited time spans and need to be renewed via their stem cells located in the bone marrow. Stem cell transplantation solves this problem by introducing cells that will be able to divide into the body of the person in need of a permanent solution.
Why would someone need bone marrow transplantation?
Bone marrow transplantation is resorted to in the following conditions:
- Hereditary diseases when either red cell production or immunity are severely impaired.
- Some red cell disorders such as Thalassemia and sickle cell anemia. Here, the bone marrow does produce enough red cells, but they are deformed and unable to carry out their function. Bone marrow transplantation is a tailored therapy according to the patient’s condition and age.
- Acquired immunodeficiency disorders, especially AIDS.
- Malignancy and premalignant conditions of the bone marrow. Leukemias are the main malignant conditions in need of bone marrow transplantation. In most cases, it is the only hope for a cure, but because of its risks, it can be second-line therapies after chemotherapy especially in older patients and those with good responses to initial chemotherapy.
- Bone marrow failure and aplastic anemia. These conditions are very diverse but they generally result from the bone marrow unable to provide enough blood cells to maintain body needs. They can result from a simple viral infection that produced a complication, radiation, drugs, chemotherapy or cancer.
Types of a bone marrow transplant
There are 2 main types of stem cell transplant:
- Autologous: In this scenario, the cells that are transplanted are collected from the same person. This may seem odd, but the collection usually follows chemotherapy as in cases of blood cancers. Then, the bone marrow is ablated and the collected cells are transfused.
- Allogenic stem cell transplantation: In this case, the transplanted stem cell comes from another person who usually has very similar surface proteins on their cells called antigens. The ideal person for such a procedure is a sibling. A subtype of allogeneic stem cell transplant is a syngeneic stem cell transplant when an identical twin is the donor. Identical twins have virtually the same genetic composition with very minor differences making them the best donor with virtually no risk of immune reactions in transplanted organs.
The bone marrow transplant procedure
Bone marrow transplantation involves the following steps:
1. Finding a suitable donor:
The bone marrow is an organ and any organ that is transplanted carries the risk of rejection. But consider this: When an organ is rejected, it is the immunity of the body that refuses its presence and considers it a foreigner, but what if the immunity itself is transplanted and considers the whole body a foreigner? This is the case in bone marrow transplantation, and that’s why many tests are carried out to ensure the suitability of the donor. The perfect donor is always the same person or an identical twin, followed by a first-degree relative. You will likely hear the term “HLA matching”. This term is short for Human Leukocytic Antigen, and this is a system by which the body identifies its own cells, much like an ID system identifiable by cells of the same body, and through HLA typing, we make sure that the body has a greater probability of accepting the marrow of the donor since it looks like its own.
It is also necessary to make sure that the donor is free of infections and malignancies at the time of donation. Any infection transmission can prove fatal to the recipient. The donor is usually carefully examined and a full medical and surgical history is taken. Basic laboratory investigations are carried out including blood count, kidney and liver functions and blood grouping, a chest x-ray may be ordered especially in smokers.
2. Conditioning:
This process involves different steps of preparing the body to receive the bone marrow. the bone marrow is ablated using chemotherapy and/or radiotherapy, to ensure the survival of the new marrow. It is worth mentioning, however, that not all patients undergo full marrow ablation especially older individuals and other alternatives are present -non-myeloablative stem cell transplantation-. This process remains a risky one, and if bone marrow rejection occurs after such ablation, the risk of adverse effects including death increases.
3. Infusion:
Infusion of the new marrow is carried out through a central venous catheter -in the neck veins for example- over a period of one hour or more.
After the previous procedures, the body becomes severely immunodeficient. This is “the neutropenic phase” because the transplanted bone marrow needs time to develop immunity after the destruction of the old one. During this period, the patient undergoes isolation to protect them from catching any infection, and antibiotics and antifungals are given even without an identifiable infection. After about 4 weeks, symptoms of immunodeficiency subside, and the patient is put under observation until discharge.
Bone marrow transplantation risks
Although bone marrow transplantation is sometimes the only available option, risks have to be considered and patients informed about the known complications of marrow transplantation. The most common problems include:
- Severe infections: Patients during the immunodeficiency phase have a nonexistent immune system and could easily develop severe infections. Most of these infections are not even possible in healthy individuals; they are so-called opportunistic infections. The sources of infections are various, but the most serious of which are the hospital-acquired ones since they are resistant to antibiotics and are therefore difficult to treat. Infections remain the most common causes of death following bone marrow transplantation.
- Cancers: Although bone marrow cancer may be an indication of bone marrow transplantation, other cancers may develop from the radiation used for destroying the old marrow.
- Graft versus host disease: This is a rejection process of the newly transplanted marrow. As mentioned above, here the marrow rejects the whole body rather than vice versa which necessitates immunosuppressive therapy and could cause severe immunodeficiency.
Umbilical cord blood and peripheral blood
Although the terms stem cell transplantation and bone marrow transplantation have been used interchangeably in this article, not all stem cell transplantation techniques use bone marrow cells. Stem cells are also found in the normal peripheral blood and the umbilical cord, and modern techniques have allowed for their collection with increasing accuracy. The first umbilical cord blood collection was actually done in the 80s.
This procedure involves the collection of umbilical cord blood from the fetal umbilical cord after clamping it at birth and then preserving it in blood banks whether national or private for future use. This can also be done as an allogeneic stem cell transplant with an increased success rate and decreased risk for graft-versus-host disease than bone marrow samples because umbilical cord cells are less mature and less differentiated to develop an immune reaction against the host.