What are Hematopoietic Stem Cells?
HSCs have the unique ability to differentiate into different types of blood cells, including red blood cells, white blood cells, and platelets. They also have the ability to self-renew, meaning that they can make copies of themselves to maintain a pool of stem cells throughout an individual's life.
HSCs are important for maintaining a healthy immune system and for repairing and replacing blood cells that are lost due to injury or disease. They are also used in certain medical treatments, such as bone marrow transplantation, to replace damaged or diseased blood cells with healthy ones.
What Is Hematopoietic stem cell transplantation (HSCT)?
Hematopoietic stem cell transplantation (HSCT) is a medical procedure that involves the transfer of hematopoietic stem cells from a donor to a recipient. These cells have the ability to develop into various types of blood cells, such as red blood cells, white blood cells, and platelets. HSCT is used to treat a variety of blood and bone marrow disorders, including leukemia, lymphoma, and multiple myeloma.
One of the key steps in HSCT is the collection of hematopoietic stem cells from a donor. There are several different techniques used to collect these cells, each with its own advantages and disadvantages. In this article, we will explore the differences between some of the most commonly used collection techniques: apheresis, cord blood, and bone marrow donation.
Autologous vs Allogeneic Stem Cell Transplantation
Autologous Stem Cell Transplantation
In this type of transplant, the patient's own hematopoietic stem cells are harvested before the procedure, usually from the peripheral blood via apheresis or bone marrow. The patient then undergoes high-dose chemotherapy or radiation therapy (known as conditioning) to eradicate the diseased cells. Once this is completed, the harvested stem cells are reinfused into the patient's bloodstream, where they travel to the bone marrow and start producing new, healthy blood cells.
Melphalan and Conditioning
Melphalan is a chemotherapy drug commonly used as part of the conditioning regimen in autologous stem cell transplantation, particularly for multiple myeloma patients. It is an alkylating agent that works by damaging the DNA of cancer cells, preventing them from dividing and eventually causing cell death. High-dose melphalan is given to the patient to kill the cancerous cells in the bone marrow, while the patient's previously collected and stored hematopoietic stem cells remain unaffected.
After the conditioning regimen has been completed, the patient's harvested stem cells are reinfused into their bloodstream, where they can travel to the bone marrow and begin to repopulate it with new, healthy blood cells. This process is essential for re-establishing a functional hematopoietic system and helping the patient recover from the disease.
Benefits of Autologous Stem Cell Transplantation
Autologous stem cell transplantation offers several advantages over allogeneic transplantation, making it the preferred choice for certain conditions when feasible. The main advantages include:
- No need for a donor: Since the patient's own stem cells are used, there is no need to find a suitable, genetically matched donor. This can save time and avoid the potential complications associated with donor searches.
- Lower risk of graft-versus-host disease (GVHD): GVHD is a major complication of allogeneic transplants, where the donor's immune cells may attack the recipient's healthy tissues, causing significant morbidity and even mortality. Since autologous transplants use the patient's own cells, the risk of GVHD is significantly reduced.
- Fewer complications related to immunosuppression: Allogeneic transplant recipients need long-term immunosuppressive medications to prevent GVHD. These drugs can cause side effects and increase the risk of infections. Autologous transplant recipients generally don't need long-term immunosuppression, reducing the likelihood of these complications.
- Faster immune system recovery: Since the patient's own immune cells are used, their immune system typically recovers more quickly after an autologous transplant compared to an allogeneic transplant. This can help reduce the risk of infections and other complications.
Diseases and Conditions Treated with Autologous Stem Cell Transplantation
Autologous stem cell transplantation is commonly used for the following diseases and conditions:
- Multiple myeloma: A type of blood cancer affecting plasma cells in the bone marrow. Autologous stem cell transplantation is often used as part of the treatment plan, in combination with chemotherapy or other therapies. This accounts for a large percentage of autologous transplants.
- Non-Hodgkin lymphoma and Hodgkin lymphoma: Autologous stem cell transplantation can be an effective treatment for certain types of lymphoma, particularly for patients who have relapsed or are at high risk of relapse after initial treatment.
- Germ cell tumors: These are rare cancers that originate in the germ cells, such as testicular cancer and ovarian cancer. Autologous stem cell transplantation can be used as part of the treatment plan for patients with relapsed or refractory disease.
- Neuroblastoma: A childhood cancer that arises from immature nerve cells, often in the adrenal glands. High-risk neuroblastoma may be treated with autologous stem cell transplantation in combination with other therapies.
- Autoimmune diseases: In certain severe cases of autoimmune diseases like multiple sclerosis or systemic sclerosis, autologous stem cell transplantation can be used to reset the patient's immune system and reduce the severity of the disease.
Allogeneic Stem Cell Transplantation
This type of transplant involves using hematopoietic stem cells from a healthy, genetically matched donor (usually a sibling or unrelated donor from a registry). The donor's stem cells are collected from either peripheral blood, bone marrow, or umbilical cord blood. The patient then undergoes a conditioning regimen, which may include chemotherapy, radiation therapy, or immunosuppressive drugs, to prepare their body for the transplant. Afterward, the donor's stem cells are infused into the patient's bloodstream, where they travel to the bone marrow and start producing new, healthy blood cells.
While allogeneic stem cell transplants can be an effective treatment for certain diseases and cancers, they carry some risks, such as graft-versus-host disease (GVHD), infections, and complications related to the conditioning regimen. The risk of complications is usually higher in allogeneic transplants compared to autologous transplants, where the patient's own stem cells are used. However, the potential benefits of the procedure often outweigh the risks for patients with life-threatening conditions.
Diseases and Conditions Treated With Allogeneic Stem Cell Transplantation
- Leukemia: Various types of leukemia, including acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), and chronic myeloid leukemia (CML), can be treated with allogeneic stem cell transplants.
- Lymphoma: Both Hodgkin and non-Hodgkin lymphomas can be treated with this procedure.
- Multiple myeloma: In some cases, patients with multiple myeloma may benefit from an allogeneic stem cell transplant, although autologous transplants are more commonly used for this condition.
- Myelodysplastic syndromes (MDS): These are a group of disorders characterized by abnormal blood cell production in the bone marrow.
- Aplastic anemia: This is a rare but serious condition in which the bone marrow fails to produce enough blood cells.
- Severe combined immunodeficiency (SCID): This is a group of rare genetic disorders that affect the immune system and can be life-threatening.
- Sickle cell disease: Allogeneic stem cell transplants can be used to treat severe cases of sickle cell disease, a genetic disorder that affects red blood cells.
- Thalassemia: This is another genetic blood disorder that results in abnormal hemoglobin production.
- Immune deficiencies: Certain primary immune deficiencies, such as Wiskott-Aldrich syndrome and Chronic granulomatous disease, can also be treated with allogeneic stem cell transplants.
- Inherited metabolic disorders: Some inherited metabolic disorders, like Hurler syndrome and adrenoleukodystrophy, can be treated with this procedure.
Hematopoietic Stem Cell Collection Methods
Peripheral Blood Stem Cells (PBSC) via Apheresis
Apheresis is a collection technique that involves removing peripheral blood (blood within circulation) from a donor, separating out the stem cells using a machine, and returning the remaining blood components back to the donor. The process takes several hours and is usually done over the course of two to three days. Apheresis is a non-surgical procedure that is generally well-tolerated by donors.
One of the main advantages of apheresis is that it allows for the collection of a large number of stem cells in a relatively short amount of time. This makes it a popular choice for HSCT in adults, where a larger number of cells are needed to ensure engraftment. However, apheresis is not as effective in collecting stem cells from pediatric donors or those with low stem cell counts. Apheresis is one of the most common techniques in modern transplantation for both auto and allogeneic purposes. Donors are typically given a drug (usually Filgrastim/Neupogen) that stimulates the bone marrow to overproduce hematopoietic stem cells among other things. This excess of stem cells can then be collected for donation.
Pros:
- Large number of stem cells: Apheresis collection can result in the collection of a larger number of stem cells compared to cord blood collection. This can be important for adult patients or patients with higher body weight who require a larger number of stem cells.
- Faster engraftment: Stem cells collected through apheresis have a faster engraftment time compared to cord blood, reducing the risk of infection and other complications.
- Greater flexibility: Apheresis can be performed on an outpatient basis, which means that donors do not need to be hospitalized for the collection process.
- Suitable for patients who have undergone chemotherapy: Apheresis collection can be used for patients who have undergone chemotherapy, while cord blood collection may not be suitable for these patients.
Cons:
- Invasive procedure: Apheresis involves inserting a needle into the donor's vein, which can be uncomfortable and may cause bruising or bleeding.
- Risk of complications: As with any medical procedure, there is a risk of complications associated with apheresis, such as infection, bleeding, or allergic reaction to the anticoagulants used during the procedure.
- Limited availability: Apheresis donors must be matched to the recipient, which can limit the availability of suitable donors.
- Higher cost: The cost of apheresis collection is generally higher than cord blood collection, and may not be covered by insurance.
Umbilical Cord Blood Stem Cells from a Cord Bank
Cord blood is a collection technique that involves collecting stem cells from the umbilical cord of a newborn baby after it has been delivered. The cord blood is stored in a cord blood bank and can be used for HSCT at a later time. Cord blood is a rich source of stem cells, and the cells are immunologically naïve, meaning they have not been exposed to foreign substances that could cause rejection in the recipient.
One of the main advantages of cord blood is that it does not require a donor to undergo a medical procedure to donate stem cells. Cord blood can also be stored for long periods of time, allowing for more flexibility in the timing of the transplantation. However, cord blood contains a smaller number of stem cells compared to apheresis, which can lead to slower engraftment and a higher risk of infection.
Pros:
- Easy collection: Cord blood is collected from the umbilical cord after birth, which is a non-invasive and painless procedure. This means that there is no risk to the mother or baby during collection.
- Availability: Cord blood can be stored in a cord blood bank for long periods of time, making it readily available for transplantation when needed.
- Low risk of infection: CB-HSCs are immunologically naïve, meaning they have not been exposed to foreign substances that could cause rejection in the recipient. This makes them less likely to cause graft-versus-host disease (GVHD) than other sources of stem cells.
- Lower risk of viral transmission: Cord blood is collected before it has been exposed to any viruses, reducing the risk of viral transmission during transplantation.
- Increased likelihood of finding a match: Cord blood is less likely to be rejected by the recipient, which means that it may be easier to find a suitable match for transplantation.
Cons:
- Small number of stem cells: The amount of CB-HSCs that can be collected is limited, which means that multiple cord blood units may need to be used for adult patients or patients with higher body weight.
- Longer engraftment time: CB-HSCs take longer to engraft and start producing new blood cells than other sources of stem cells, which can increase the risk of infection and other complications.
- Higher cost: The cost of collecting, processing, and storing cord blood is higher than other sources of stem cells, and may not be covered by insurance.
- Limited uses: CB-HSCs may not be suitable for all types of blood and bone marrow disorders, and may not be effective for treating certain advanced or aggressive diseases.
Stem Cells via Bone Marrow Donation
Bone marrow donation is a surgical procedure that involves extracting stem cells from the bone marrow of a donor. The donor is given anesthesia, and a needle is inserted into the hip bone (Iliac Crest) to extract the marrow. The procedure takes about one to two hours, and donors may experience soreness and fatigue for a few days after the procedure.
Pros:
- Large number of stem cells: Bone marrow donation can result in the collection of a large number of stem cells, which can be important for adult patients or patients with higher body weight who require a larger number of stem cells.
- Faster engraftment: Stem cells collected from bone marrow have a faster engraftment time compared to cord blood, reducing the risk of infection and other complications.
- Low risk of complications: The risk of complications associated with bone marrow donation is low. Donors are given anesthesia during the procedure, and may experience some soreness or stiffness in the lower back for a few days after the procedure.
- Greater flexibility: Bone marrow donation can be performed on an outpatient basis, which means that donors do not need to be hospitalized for the collection process.
Cons:
- Invasive procedure: Bone marrow donation involves the insertion of a needle into the donor's pelvic bone, which can be uncomfortable and may cause bruising or bleeding.
- Recovery time: Donors may experience soreness or stiffness in the lower back for several days after the procedure, which can limit their ability to perform certain activities.
- Limited availability: Suitable donors for bone marrow donation must be matched to the recipient, which can limit the availability of suitable donors.
- Higher cost: The cost of bone marrow donation is generally higher than cord blood collection, and may not be covered by insurance.
Hematopoietic Stem Cell Transplant Success Rates
The success rate of a stem cell transplant can vary depending on several factors, including the type of transplant, the age and health of the patient, the stage and type of the disease being treated, and the quality of the match between the donor and the recipient.
For autologous transplants, where the patient's own stem cells are used, the success rate is generally high, with a 90% or higher survival rate for some types of cancers, such as multiple myeloma and lymphoma.
For allogeneic transplants, where stem cells are obtained from a donor, the success rate can vary depending on several factors. A major factor affecting success is the degree of HLA (Human Leukocyte Antigen) matching between the donor and the recipient. HLA matching is used to determine how closely the donor's immune system matches that of the recipient. The closer the match, the better the chances of a successful transplant.
For HLA-matched siblings, the success rate of an allogeneic transplant is approximately 80-90%. For unrelated donor transplants, the success rate can range from 40-60%, depending on the degree of HLA matching, the age and health of the recipient, and other factors.