Fortis Hiranandani Hospital
Mumbai,India
The human skeletal system comprises of various bones. At the inner side of some bones such as thigh and hip bones, a soft-spongy tissue is present. This soft-spongy tissue is known as bone marrow. Bone marrow may also present in ribs, vertebrae, and cranium.
Sometimes you come across various transplantation terms such as bone marrow transplantation and stem cell transplantation. What is the difference between bone marrow and stem cells? Bone marrow comprises of two types of stem cells. One is the hematopoietic stem cells which can differentiate into various blood cells and the other one is stromal stem cells which produce cartilage, bone, and fats. In almost all the cases of bone marrow transplantation, the hematopoietic stem cells that get transplanted. Some of the hematopoietic stem cells get released in the bloodstream from bone marrow. These stem cells can also be used for transplantation.
Hematopoietic stem cells may give rise to various types of blood cells depending upon the requirement. These stem cells may transform either to RBC (Red Blood Cells), which carries oxygen throughout the body or to the WBC (White Blood Cells) that helps the body in fighting against infections or blood platelets that help blood clotting in case of injury.
Bone marrow transplantation is the process of replacing the damaged or abnormal bone marrow with healthy bone marrow stem cells. In actual sense, the stem cells get transplanted, thus the process is also known as stem cell transplantation.
When the transplanted stem cells are derived from bone marrow, the method is termed as bone marrow transplantation, and when the stem cells for transplantation are taken from blood, more accurately the peripheral blood, the procedure is known as peripheral blood stem cell transplantation or simply stem cell transplantation. However, in a general sense, all types of stem cell transplantation whether hematopoietic stem cell transplant (HSCT), peripheral blood stem cell transplant (PBSCT) and bone marrow stem cell transplant comes under the broad umbrella of Bone Marrow Transplantation.
Following are the different types of bone marrow transplantation depending upon the type of donor:
Autologous Bone Marrow Transplantation: In this type of bone marrow transplantation, the patient himself is the donor of stem cells. The stem cells are collected from the recipient before any high level of chemotherapy or radiotherapy which may destroy all the stem cells. The stem cells are refrigerated until they are required for transplantation. The collected stem cells are used to replace the destroyed stem cells.
Allogeneic Bone Marrow Transplantation: In cases where the autologous bone marrow transplantation is not feasible, stem cells of the genetically matched stem donor is transplanted. The donor is usually a sibling of the patient.
Matching Unrelated Donor Bone Marrow Transplantation: This type of bone transplantation is an alternative to those patients who are not able to get the matched sibling. Often found through bone marrow registries, these donors are not the relative of patients yet they have matched human leukocyte antigen.
Haploidentical Bone Marrow Transplantation: Haploidentical bone marrow transplantation is a relatively new technique in bone marrow transplantation. In cases when the patient is not able to get related or unrelated identical stem cell donor, a haploidentical donor may donate the stem cells. A haploidentical donor is a person who has at least 50% match to the patient or recipient. With the advancement of technology and new treatment options, complications after the transplant can be managed. The haploidentical donor may be siblings, parents or children.
Bone marrow transplantation is a process of replacing the older stem cells with newer stem cells. The new stem cells may either be collected from the recipient himself or a donor. This depends upon the disease to be treated through transplantation. A stem cell may be extracted either from bone marrow or from peripheral blood. Most of the current transplant procedures involve the stem cells collected from peripheral blood. The bone marrow transplantation involves the following steps:
Increasing The Number Of Stem Cells In Peripheral Blood: This process is done when the stem cells are collected from the peripheral blood. Medicines are usually administered to increase the number of stem cells in the blood. This process is not done in case stem cells are collected from the bone marrow.
Collecting The Stem Cells: Process of collecting stem cells is different for bone marrow and peripheral blood. While the collection of stem cells from bone marrow is a surgical process, it is non-surgical in case of peripheral blood. Stem cells are collected from bone marrow under anesthesia. A needle is inserted in the middle of the pelvic bone and bone marrow is extracted with the help of a syringe. It takes around 1-2 days of extraction to get a sufficient amount of bone marrow for a transplant. Collection of stem cells from peripheral blood is done through a specialized machine. The blood exits from the body through a tube connected to a vein in one arm, enters the machine where the stem cells are extracted and returns into the body through another arm.
Freezing Stem Cells: Once the stem cells are collected, freezing is done in the laboratory until they are required.
Conditioning: Conditioning is the process of killing the remaining stem cells to make space for new stem cells. Conditioning is done through chemotherapy and/or radiation therapy. In some cases, conditioning is performed to completely or partially eliminate the immune system.
Transplanting Stem Cells: Freeze stem cells are thawed before transplanting. The stem cells are then infused in the recipient’s body through a large vein, usually of the chest. The donor cells circulate in the bloodstream and migrate to the bone marrow where they start producing new and healthy cells.
Supportive Medical Care: Supportive medical care is an important step for a successful transplant. The patient should be protected from infection and Graft-versus-host disease. Intensive care is provided for at least 4-6 weeks as the immune system of the recipients build.
Bone marrow is largely responsible for the formation of various types of blood cells such as RBC, WBC, and platelets. The diseases which can be treated with bone marrow transplant, are thus, generally related to blood. It has been found that bone marrow transplant may help in curing more than 70 diseases ranging from common blood cancer to rare diseases like polycythemia vera. Following is a comprehensive list of diseases that can be treated with bone marrow transplant:
Human Leukocyte Antigen (HLA) is a protein present on cells. The immune system of the body identifies HLA to decide whether to initiate an immune response against a particular cell. For example, if the immune cells come in contact with the body cells, the information gets processed through HLA matching and the immune system does not initiate any response against those cells. However, when there is any bacterial infection in the body, the cells of the immune system, through HLA mismatch, identifies them as foreign cells and initiates an immune response against them thereby killing those bacterial cells.
A similar process applies to the transplanted stem cells obtained from a donor. The stem cells have HLA on the surface. If the HLA of donor stem cells matches the HLA of host cells, the immune system does not attack the transplanted cells and the chances of a successful transplant is high. The severity of immune response depends upon how closely the HLA of donor matches with the host’s HLA.
The matching of HLA is done based on 8 or 10 markers. For a successful and favorable bone marrow transplant, a greater number of HLA markers should match. Half of the HLA markers are inherited from mother and half are inherited from father. Thus, there is a 25% chance of a complete match, 50% chance of matching half markers and 25% chances of not matching any of the markers.
Almost 70% of people requiring transplant do not have a complete match within the family. In very rare cases, an unrelated donor may have a complete match. When the bone marrow transplantation is advised, the sample of siblings is taken to match the HLA markers. In case the sibling is not a proper match, samples of other family members such as parents or children are taken. If the matching fails, the medical staff of the hospital may contact the concerned authorities to search in the International registries for getting the best match from an unrelated donor.
Conditioning chemotherapy is a step performed during bone marrow transplantation. It is generally done through chemotherapy which may or may not be complemented with radiation therapy.
Induction chemotherapy is also known as adjuvant chemotherapy. This chemotherapy is done before surgery or radiation therapy. Induction chemotherapy is done according to the principle of spatial cooperation. In previously untreated patients, systemic chemotherapy is recognized as a highly active treatment regimen.
Conditioning in bone marrow transplantation is done due to the following reasons:
When the symptoms of cancer are reduced or disappeared, the disease is said to be in remission. There is no way for the doctor to find all the cancerous cells in the body, so if the symptoms of cancer are completely gone, they prefer to use the term “remission” rather than “cure”.
In case of life-threatening diseases such as acute myelogenous leukemia (AML), bone marrow transplantation according to the timing of remission has an impact on overall survival rate. The 5-year survival rate is around 30-50% in people suffering from AML if the allogeneic stem cell transplant is done during the period of the first remission. The person has an 80% chance of staying in remission if there is no recurrence of disease in the initial two years after stem cell transplant.
Apart from chemotherapy, sometimes radiation therapy is also performed during the conditioning process. The main aim of radiation therapy is to kill those cells that have escaped the effect of chemotherapy. Further, the decision to combine chemotherapy and radiation therapy may also depend upon the side effect of the overall conditioning process. Effectiveness of Total Body Irradiation (TBI) depends upon fraction size, delivered dose, and dose rate. Radiation therapy is also used to suppress the immune system.
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Bone marrow transplant drains you emotionally, physically and mentally. So it is advised that before the procedure gets started you should prepare yourself for bone marrow transplant. Following guidelines may help you in preparing for this process:
Like any other medical treatment, the overall cost of bone marrow transplant also depends upon a variety of factors. These factors are either related to the patient himself or to the hospital and the surgeon conducting bone marrow transplant. Following are some of the factors affecting the cost of bone marrow transplant:
Following are the approximate charges for bone marrow transplant in various countries and may vary greatly in various hospitals of the same country:
Country | Cost of Allogenic Transplant (USD) | Cost of Autologous Transplant (USD) |
India | 40,000 | 22,000 |
Singapore | 75,000 | 50,000-55,000/td> |
US | 6,00,000-8,00,000 | 3,50,000 |
UK | 8,00,000 | 3,50,000 |
Thailand | 70,000 | 60,000 |
Malaysia | 65,000 | 45,000 |
Turkey | 70,000 | 50,000 |
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Most people have expressed that their quality of life has been improved after having a stem transplant. Further, it is also exciting for some to have another life.
Recovery after a stem cell transplant is a slow process. The body is drained after chemotherapy and/or radiotherapy and transplant process. After emotional, mental and physical stress before and during transplant patient requires sufficient rest to regain lost energy.
Discharging from Hospital: You may get discharged from the hospital when your blood counts have reached a safe level and you have sufficiently recovered from side effects. Further, you may also able to walk on yourself and does not require the drug to be administered through injections/injection lines.
Preventing infection: Your immune system is at an all-time low and the risk of infection is drastically increased. You should take extra care of yourself. Wash your hands with alcohol-based sanitizers and stay away from sick people.
Follow a Healthy Lifestyle: Follow a healthy lifestyle during the recovery period. Certain foods, that carries a risk of infection should be avoided and a healthy and balanced diet should be maintained.
Follow-Up Visit: Follow-up visit schedule is provided to the patient and the patient should strictly adhere to this schedule. For the first few months, the patient has to visit the hospital more frequently. As the condition and vital parameters of the patient gets stable and the recovery of the patient is on track, the frequency of hospital visit gets reduced. It is important to note that the frequency of follow-up visits in case of autologous transplant is low as compared to allogeneic transplantation.
Routine Activities: For improving the muscle tone, you can take a gentle walk. As the blood count increases, the period of exercise can gradually be increased. Drive only when you are comfortable with it. As the body is undergoing a recovery phase, it is hard to concentrate on driving because of tiredness. Further, side effects of certain medicines may also affect your ability to drive.
Stem cell transplantation is a complex procedure and various drugs are prescribed for successful bone marrow transplantation. In some cases, radiation therapy after bone marrow transplantation is also recommended.
Radiation Therapy: In some cases, chemotherapy is not able to kill all the cancer cells. In such cases, radiation therapy is advised.
Antibiotics: Antibiotics are prescribed to reduce the risk of infection as the immunity of the patient is at a minimum level.
Immunosuppressive Drugs: To prevent Graft-versus-host disease, immunosuppressive drugs are prescribed. The immunosuppressive drugs are commonly used in a patient undergoing allogeneic stem cell transplant.
Supervision: Follow-up visit and strict supervision are the keys for successful bone marrow transplant. The patient should undergo regular check-up and should be under the strict supervision of the transplant surgeon.
#1: How is a bone marrow match determined?
A: Human Leukocyte Antigen (HLA) is used to match donors to patients. HLA is a type of protein present on most of the body cells. Various HLA markers are present that makes a particular tissue unique. Some markers play an important role in bone marrow transplant. These markers are required to be matched in the donor-patient group. If more than one closely matched donor is found, the doctors then decide the donor based on age, gender, height, weight, and blood type.
#2: How are bone marrow and peripheral blood stem cell (PBSC) donation different?
A: If you want to donate the stem cells, you have two options available. One is the bone marrow donation while other is peripheral blood stem cell donation. While bone marrow donation is a surgical process, peripheral blood stem cell donation is a non-invasive process. As the number of stem cells in blood is less, if you choose peripheral blood stem cell donation, daily injections of Granulocyte colony-stimulating factor are administered to increase the number of stem cells in peripheral blood. Peripheral blood stem cell is not a long process while bone marrow donation procedure takes around 60-minutes to 90-minutes. As peripheral blood stem cell donation is a non-surgical method, it is the most commonly used procedure.
#3: Can there be any medical complications for Bone Marrow Transplantation?
A: Due to advancement in technology and highly sophisticated instruments used during the stem cell donation process, the medical complications are minimal in context to the donor. Complications reported in some donors include respiratory disturbances, splenic rupture, and trigger of inflammatory reactions.
#4: Are there any side effects of Donating your Bone Marrow?
A: The side effects of the donation process are not severe. Muscle pain, headache, nausea and vomiting, and bone pain are common side effects of peripheral blood stem cell donation while the risk of infection, pain, and numbness, bruising, bleeding and feeling of discomfort are associated with bone marrow donation. In most cases, the side effects disappear after a few days.
#5: What can I do to recover well after donation?
A: Your recovery time varies with the process of stem cell donation. If you have donated the stem cell through peripheral blood stem cell, you can fully recover within seven days, while donating stem cells through bone marrow requires approximately 20 days to get fully recovered. However, the recovery depends upon your age and the side effects experienced by you during or after the procedure. In most cases, the donors return to have their routine activities within a week after donation.
#1: How long will the entire treatment be?
A: The complete procedure of bone marrow transplantation is divided into various stages. Time taken in each step depends upon the condition of the patient. Following are the stages and duration of bone marrow transplantation:
Comprehensive Health Evaluation: Not all candidates qualify for bone marrow transplantation. It depends upon the age of the patient and overall health status. This may include any underlying disease, and capacity of the patient to cope with the procedure. Complete health evaluation may take a few days to a week.
Conditioning: After the doctor certifies that you are fit to undergo bone marrow transplantation, you have to go through a process known as conditioning. As you are about to receive new cells, old cells are to be removed to clear the space in bone marrow or to kill cancerous cells. Depending upon your condition, the doctor may perform chemotherapy or radiotherapy. This takes around a week depending upon the sessions of therapy required.
Transplant Procedure: After a couple of days of conditioning, you may undergo the transplanting procedure. Process of transplantation is simple and does not involve any surgery. The stem cells are infused in the body through the central line.
#2: Do I have to bring the donor with me?
A: The best donor is the person having the highest number of HLA markers matched. The genetically matched donor is preferred. Normally this would be your brother or sister. So, if your sibling consents to provide you with his/her stem cells, he/she has to undergo a comprehensive evaluation. After evaluation, if all the markers are matched and other tests are fine, stem cells from your sibling can be taken. However, if the markers are not matched, the next option is to find the unrelated match donor. The transplant center may send information related to your tissue type to various marrow registries to find a suitable donor for you. So, it is not always possible that the donor you bring can donate the stem cells.
#3: When can I return to work after my Transplantation?
A: Returning to work would depend upon the type of transplantation you have undergone and the speed of your recovery and is considered as an important milestone in the complete recovery process after stem cell transplant. It helps you to feel normal again. However, do not rush yourself to go to work. Take advice from your doctor before stepping out from your home as your immune system is not in the best of the condition. The doctor may also consider the nature of your job before permitting you to resume your job. For instance, if your job is physically demanding, you have a higher risk of getting infected and thus the time for returning to work may be relatively longer. Generally, it may take anywhere between 9 months to 12 months to make you completely fit for working again.
#4: Will there be any side effects after my Transplantation?
A: You may have various side effects based on whether you have undergone allogeneic transplant or autologous transplant. Most side effects occur due to radiation therapy or chemotherapy. It is to be noted that your immune system might not achieve similar activity after bone marrow transplant.
If you have undergone autologous bone marrow transplantation you may have the following side effects:
Infection: As your bone marrow is responsible for generating cells that fight against the infectious organism, destroying bone marrow cells through chemotherapy/radiation therapy increases the risk of infection. This risk is very high in the initial weeks after transplant. Another risk is of opportunistic infection. Pathogenic organisms are living in the body and are kept under check by the immune system. As the immune system becomes weak, these pathogens may cause infections. Some patients require a year-long course of antivirals and antibiotics.
Short term side effects: You may experience the following side effects immediately after bone marrow transplantation:
Long term side effects: You may have side effects that may occur months or years after bone marrow transplant. These side effects include:
If you have undergone the allogeneic bone marrow transplantation, you may experience the following side effects:
Infections: Your risk of infection is similar to a person undergone autologous bone marrow transplantation; however, you may have the risk of infection relatively for a longer period. This is because, apart from giving you the radiotherapy and chemotherapy, the doctor may also prescribe you drugs for suppressing the immune system. These drugs will prevent your immune system from attacking the new stem cells.
Graft-versus-host disease: Stem cells may attack the vital organs of your body. This may occur even if you have a 100% matched donor. The GVHD may be moderate or severe. Fortunately, this side effect is rarely life-threatening. You may have GVHD in two stages:
P.S.:You may experience short term and long-term similar to the recipients undergone autologous bone marrow transplantation.
#5: How are my stem cells collected for my bone marrow transplant?
A: The process of collection of your stem cell depends upon the collection site. Stem cells can be collected from either bone marrow or the peripheral blood.
Collection of stem cells from peripheral blood: Most of the stem cell transplantations are currently done through the peripheral stem cell collection. Before the collection of the stem cells, you may be prescribed medicines such as filgrastim or plerixafor for 4-5 days to increase the number of stem cells in the blood. In autologous bone marrow transplant, drugs used in chemotherapy may also be administered to move the stem cells out from the bone marrow and circulate them into the blood. During this process, the needle connected to a thin tube is inserted on veins of each arm. The blood is withdrawn from one arm, passed through a machine which separates the stem cells from blood and the blood is returned to the body through the other arm. Generally, the process continues for around three hours. For collecting enough stem cells, the process is repeated for the next couple of days.
Collection of stem cells from bone marrow: Although collecting the stem cells from bone marrow involves surgery, it is done as an outpatient procedure. The procedure is done under anesthesia and a needle is introduced in your pelvic bone. The pelvic bone is chosen due to the presence of a large number of stem cells. Stem cells are taken with the help of a syringe. Only the skin punctures are done for extracting the stem cells and there would not be any incision on your skin. You may have several punctures to extract a sufficient amount of stem cells. A sterile bandage is placed at the site of collection.
#6: Is spinal tap painful?
A: Cerebrospinal fluid is present in your brain and spinal cord and protects them from injuries. Spinal tap, also known as lumbar puncture, is the process done to take the sample of your cerebrospinal fluid to diagnose various diseases such as leukemia or meningitis. In this process, the fluid is removed by inserting a needle in the space between two lumbar vertebrae. Sometimes you may also have a spinal tap to administer chemotherapy drugs or anesthetics. Although spinal tap is recognized as a safe procedure, you may have the following effects after spinal tap:
#7: How long does chemotherapy/radiation last before bone marrow transplant?
A: While getting prepared for bone marrow transplantation, you have to undergo a conditioning regimen. During the conditioning process, chemotherapy or/and radiation therapy is used to kill the cells or to prevent your body from rejecting the transplanted stem cells. The goal of conditioning regiment is to make space for new cells, and killing the cancerous cells present. The days and intensity of conditioning regimen depend upon the type of disease, age, presence of underlying medical diseases, and diagnosis and remission status. If you are with severe immunodeficiency or having severe aplastic anemia, your doctor may skip the conditioning regimen. Chemotherapy may be complimented with radiation therapy if required. Chemotherapy or radiation therapy may last for 5 to 7 days.
#8: What precautions do I have to take after the procedure?
A: Because of the suppressed immune system and reduced level of blood cells, you have to take precautions to prevent yourself from infection and bleeding. Following are some of the precautions you should follow after transplant procedure:
#9: Do blood and platelets have to be arranged on our own during the process?
A: You may require blood and platelets if the number of blood cells is below the critical level. Talk to the hospital administration department about the availability of blood bank in hospital. Many large Superspeciality hospitals have blood bank associated with them. If you have donated blood previously during any blood donation camp, you may be provided with a blood bank card. However, you may eligible for receiving a limited amount of blood-based on that card. Thus, it is advised to arrange the family members for donating blood as you may require more blood during or after the transplant process.
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