All living organisms started life from one cell. As humans, life started as a zygote, which is the fusion between a female ovum and a male sperm. Therefore, all of our cells originated from one, and this one cell undergoes division into different “lines” of cells that subdivides further into more specialized types. Blood cells originate from a specific line of cells called hemopoietic stem cells. The site of such cells differs according to the stage of the human embryo, but by the time a human fetus is born, all of their hemopoietic stem cells are located in their bone marrow. The bone marrow is located in a cavity within the long bones, like those of our arms and legs, and some bones in our axial skeleton which includes the skull, ribs and pelvis.
The bone marrow is broadly classified into two types: red or “active” marrow which contains active cells that divide repeatedly to supply new cells, and yellow or “inactive” bone marrow which contains more fat and less active cells. When a human fetus is born, most of his marrow is active but as he or she ages, their bone marrow gradually transforms into the inactive form. By adulthood, most of our marrow in long bones becomes yellow except for a few sites in our central skeleton, mostly the ribs, pelvis and our breastbone, the sternum. This is not an absolute fact and, in many conditions, whether in disease or in response to some drugs, our yellow marrow may transform into the red type to satisfy the need of the body for more red cells or in response to an artificially administered stimulant such as erythropoietin.
What is stem cell transplantation?
Organ transplantation 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 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 such cells which are able to divide into the body of the person in need for a permanent solution.
Why do we transplant bone marrow stem cells?
Bone marrow transplantation is resorted to in the following conditions:
- Hereditary diseases where 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. The choice of bone marrow transplantation is a tailored one according to the patient’s condition and their age.
- Immunodeficiency disorders, especially AIDS.
- Malignancy and premalignant conditions of the bone marrow. Leukemias are the main malignant condition requiring bone marrow transplantation. In most cases it is the only hope for cure, but because of its risks, they can be second-line therapies after chemotherapy especially in older patients and those with a good response to initial chemotherapy.
- Bone marrow failure and aplastic anemia. These conditions are very diverse but they generally result from a bone marrow that is unable to provide enough blood cells to maintain body requirements. They can result from a simple viral infection that produced a complication or from malignancy.
The procedure
Bone marrow transplantation involves the following steps:
i. Finding a suitable donor
The bone marrow is an organ, and any transplanted organ 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 system is the one being transplanted and considers the whole body as a foreigner? This is a possibility 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 it is a system by which the body identifies its own cells, where it serves as an ID between cells of the body, and through HLA typing, we make sure that the body has a greater probability of accepting the marrow transplant.
ii. Conditioning
This process involves different steps of preparing the body to receive the bone marrow. The present marrow is ablated using chemotherapy and radiotherapy to make a space for the new marrow. It is worth mentioning, however, that not all patients undergo full marrow ablation, especially older individuals. This process remains a risky one, and if bone marrow rejection occurs after such ablation, the risk of adverse effects increases, including mortality.
iii. Infusion
Infusion of the new marrow is carried out though 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. It is “the neutropenic phase”, which occurs 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 in the absence of 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 may easily develop severe infections. Most of them are not even possible in healthy individuals; these are the so-called opportunistic infections. The sources of infections are various, but the most serious are hospital-acquired since they are resistant to antibiotics and are therefore difficult to treat. Infections remain the most common cause 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 to destroy the old marrow.
- Graft versus host disease: A rejection process of the new 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.
Bone marrow donation
Since the bone marrow is an organ and transplantation is sometimes considered the only definitive treatment in many conditions, bone marrow donation is an integral part of any healthcare system. All body organs are “coded” with receptors on the surface of their cells which serve as an ID to tell the immune system that they belong to the same body. They are called MHC or “Major Histocompatibility complexes”.
When transplanting an organ, we have to make sure that both the transplanted organ and the body are compatible to prevent the development of graft versus host reaction or “rejection”. Therefore, transplanted organs from the body itself or from an identical twin are unparalleled and need no special measures for immunosuppression, followed by those from close family. Stem cells can be taken both from the bone marrow itself or from the peripheral blood.
Bone marrow donation risks
Bone marrow donation is a relatively safe procedure and carries no risks other than those related to the setting of the procedure itself. In case of bone marrow donation from the marrow itself, the main risk is that of the anesthesia, and the small wound found at the back of your pelvis will be no more than a few centimeters across.
Peripheral bone marrow donation is much safer and carries minimal risks. The choice of the type of donation, however, depends on the amount needed and the resources available at the hospital to obtain enough blood stem cells from the peripheral blood.