Overview of Hematopoietic Stem Cell Transplantation
A Hematopoietic stem cell transplant (HPSCT), also known as a bone marrow transplant, is a procedure that involves giving healthy stem cells to patients whose bone marrow is not functioning properly or is depleted. This transplant can increase the functionality of the bone marrow. Depending on what illness is being treated, it might also be able to destroy cancer cells. Additionally, it can create healthy cells to replace any that are not working properly in conditions such as immune deficiency syndromes, blood disorders, and other diseases.
The use of Hematopoietic stem cell transplantation (HPSCT) in humans began in the 1950s. It was originally studied in mice where healthy bone marrow parts were infused into mice with dysfunctional bone marrow, which then improved the overall health and function of the recipient’s bone marrow. This method was first applied to humans successfully in 1957, when a bone marrow transplant was performed between identical twins in New York to treat acute leukemia. The doctor who performed this procedure, E. Donnell Thomas, continued to research and develop this method, and was later awarded the Nobel Prize for Physiology and Medicine for his work. In 1968, the first successful transplant involving a donor and a recipient who were not identical twins (known as an allogeneic transplant) was reported in Minnesota for a pediatric patient with severe combined immunodeficiency syndrome.
Since then, these transplants from both the patient themselves (autologous) and from another donor (allogeneic) have increased in the United States and abroad. For example, in 2016, there were over 8,000 allogeneic transplants performed in the U.S. alone, and an even larger number of autologous transplants.
There are a few terms that are important to know.
Human Leukocyte Antigens (HLA) and Major Histocompatibility Complex (MHC) are proteins that live on the surface of our cells. These proteins have a major role in how our immune system functions. MHC is split into two classes which result in different types of cell-surface proteins.
If the donor and patient are identical twins, this is known as Syngeneic Bone Marrow Transplantation. This type of transplant has no risk of the patient’s body rejecting the transplant or of the transplant failing; however, not every patient will have an identical twin available for transplantation.
Autologous Bone Marrow Transplantation is when the patient themselves is the donor. The bone marrow is collected from the patient and then purified and reinfused. There’s no risk of the patient’s body rejecting the transplant, but sometimes, abnormal cells might be included in the reinfused marrow, which could cause a relapse in the case of a disease like cancer.
Allogeneic Transplantation is when a family member who is a good genetic match, an unrelated donor who is a good genetic match, or a half-matched family donor is the one donating the bone marrow.
Engraftment refers to the process where the transplanted stem cells start to produce mature offspring in the patient’s body.
Preparative Regimen is the treatment plan involving high-dose chemotherapy or full-body radiation (total body irradiation TBI) or both. This is given to the patient before the stem cell infusion to kill off as many malignant cells as possible and suppress the patient’s immune system to allow for successful engraftment.
Why do People Need Hematopoietic Stem Cell Transplantation
Some medical conditions can threaten a person’s life, and treatments such as stem cell transplantation may be recommended. Stem cell transplantation is a procedure that replenishes healthy cells in a person’s body after they have been destroyed by disease or aggressive treatments like chemotherapy. Let’s look at how this treatment can help with different diseases.
For patients under 65 with a condition called multiple myeloma, survival rates are found to increase when they receive a stem cell transplantation following specific drug therapy with a medicine called melphalan, which is followed by a drug called lenalidomide. Multiple myeloma is a type of cancer that affects plasma cells in the bone marrow.
For people who have either Hodgkin or Non-Hodgkin lymphomas and haven’t done well on their first treatment, it has been found that initial chemotherapy followed by a stem cell transplant has better outcomes. Both Hodgkin and Non-Hodgkin lymphomas are types of cancers that begin in a certain kind of white blood cells.
In case of a type of blood cancer known as acute myeloid leukemia or AML, which does not respond well to the first treatment, stem cell transplantation can lead to enhanced life expectancy. Similarly, in cases of a different blood cancer called acute lymphocytic leukemia or ALL, stem cell transplantation is recommended if the initial treatment doesn’t manage to control the disease.
For particular types of blood cell disorders known as myelodysplastic syndromes or MDS, stem cell transplantation can be a game-changer, but it’s only directed towards patients who have a moderate or high degree of risk. In the occurrence of other types of leukemias known as chronic myeloid and chronic lymphocytic leukemia, stem cell transplantation is reserved for patients whose disease does not respond to other treatments.
On the other hand, solid tumors like testicular cancers that do not respond well to chemotherapy can be treated with stem cell transplants. This procedure has also been considered for treating other cancer types, like metastatic breast cancer.
Beyond cancer, stem cell transplantation has benefited patients with non-cancerous conditions too. For instance, in patients with a condition known as aplastic anemia wherein the body stops producing enough new blood cells, transplantation has resulted in better outcomes compared to some traditional treatments. Other diseases, such as severe combined immune deficiency syndrome (SCID), thalassemia, and sickle cell disease, can also be treated with stem cell transplantation leading to improved survival rates.
Stem cell transplantation is also being considered for treatments related to autoimmune diseases such as systemic sclerosis and systemic lupus erythematosus and has shown effective results in conditions like neuromyelitis optica and multiple sclerosis.
When a Person Should Avoid Hematopoietic Stem Cell Transplantation
There aren’t any situations where a hematopoietic stem cell transplant, which is a procedure that replaces damaged or destroyed blood stem cells with healthy ones, is completely unsuitable or not allowed.
Equipment used for Hematopoietic Stem Cell Transplantation
There is specific tools and technology designed for the process of collecting, keeping safe, and delivering stem cell products. These stem cell products are used in treatments that help the body to heal itself.
Who is needed to perform Hematopoietic Stem Cell Transplantation?
An interprofessional team approach means that different healthcare professionals work together. This is the best way to make sure that stem cells are collected and given to the patient in a safe and effective way.
Preparing for Hematopoietic Stem Cell Transplantation
Getting ready for the procedure involves several key steps.
First, the patient undergoes an intense treatment called a preparative regimen. This can include high-dose chemotherapy, total body irradiation (TBI), or both. Chemotherapy is a strong drug treatment that kills cancer cells, while TBI is a form of radiation therapy that targets the whole body.
Next, doctors collect hematopoietic stem cells. These are cells found in the bone marrow that can turn into different types of blood cells. These cells can help the body recover from the chemotherapy and TBI used during treatment.
Finally, the collected stem cells are either instantly infused back into the patient’s body or they are cryopreserved. Cryopreservation is a process where cells are frozen for later use. Whether the cells are infused immediately or frozen for later, they will eventually be returned to the patient’s body. This helps regenerate healthy blood cells to replace those killed off by the intense treatment.
How is Hematopoietic Stem Cell Transplantation performed
The method in which Hematopoietic Stem Cell Transplants (HPSCT, a medical procedure where stem cells are extracted and then injected back into the body) work for leukemia patients is based on the impact of the transplant and the immune response of the donor against dangerous cells in the patient’s body. This effect was shown in a study of over 2000 patients suffering from various types of leukemia who were treated with HPSCT. Those patients who had the lowest rates of the disease came back were those who got normal bone marrow cells (non-T-cell-depleted) and those who had a certain kind of body reaction (GVHD). This suggests that the immune system of the donor plays a crucial role in the effectiveness of the transplant.
As for patients with autoimmune diseases, it’s thought that HPSCT works by increasing the regulation of T-cells, a type of white blood cell that is key to the immune system. This increased regulation can promote a more balanced immune response. Meanwhile, in diseases related to hemoglobin (a protein in red blood cells), the transplanted stem cells develop functional cells that take over the role of the disease-infected cells. However, more studies are needed to understand the exact process behind this.
Human Leukocyte Antigen (HLA) typing is crucial to finding the best match for a stem cell donor. An ideal match is typically a related person, followed by an unrelated match, cord blood, and then a ‘half-identical’ donor. HLA determines the compatibility between the donor and the recipient at either a lower-resolution level (detecting a small number of matched genes), or at a high-resolution level (to determine the specific number of matching genes). This process is carried out using procedures called a Polymerase chain reaction and next-generation sequencing. The higher the number of matching HLA types, the better the survival and outcome.
The process of HPSCT changes depending on where the stem cells are collected from (i.e., bone marrow, peripheral blood, or cord blood) and whether the stem cells are coming from the patient themselves (autologous), from a donor (allogeneic), or from an identical twin (syngeneic). Broadly, the HPSCT procedure involves first mobilizing stem cells, followed by a preparatory regimen, and finally infusing the cells back into the patient’s body.
Starting the HPSCT involves using medication to boost the number of stem cells in the blood, as our blood naturally doesn’t have many stem cells. Certain factors or drugs can push the stem cells out from the bone marrow into the blood. For example, Granulocyte Colony-Stimulating Factors (G-CSF) can trigger white blood cells to release proteins that encourage stem cells to leave the bone marrow.
Following the mobilization of the stem cells, the next process is the preparative regimen, which is the delivery of chemotherapy with or without full body radiation (total body irradiation). This process is designed to erase harmful cells and ensure the patient’s immune system accepts the new cells. Once the preparative regimen has been completed, the infusion of the stem cells can take place. This is usually done in a clinic and can take up to two hours. Before the infusion begins, the cells are checked to ensure there are enough to ensure a successful transplant.
The benefits and drawbacks of HPSCT depend on the source of the stem cells. Peripheral blood stem cells (commonly used in PBSCT), for instance, graft quicker than bone marrow cells.
Possible Complications of Hematopoietic Stem Cell Transplantation
After a bone marrow transplant, there can be short-term (acute) or long-term (chronic) complications. These complications can be influenced by many factors such as a person’s age, health status before the transplant, the type of stem cell transplant and the intensity of treatment used to prepare for the transplant. The first 90 days after the transplant are when most acute complications happen. These may include extremely low blood cell counts, damage to liver vessels, mouth ulcers, severe immune reactions (graft versus host disease), and various infections. Later on, complications might include ongoing immune reactions, infections, and flare-ups of the chickenpox virus.
After the transplant, patients are usually given preventative (prophylactic) medications to stop infections. For instance, Levofloxacin is given right from the first day after the transplant until white blood cell counts increase or immunosuppressive medication is stopped. To prevent pneumonia in these immune-compromised patients, medications like Trimethoprim-sulfamethoxazole are used. Other prophylactic treatments include antifungal and antiviral medications to prevent infections.
A special condition that can occur with cord stem cell transplants is cord colitis, which causes diarrhea and is thought to be due to a bacteria called Bradyrhizobium enterica. Antibiotics like Metronidazole or Levofloxacin can usually treat this condition.
One serious complication that can occur after a transplant is Sinusoidal obstruction syndrome (SOS), which can cause liver damage. This condition typically happens due to the chemotherapy used in preparing for a transplant. Symptoms include liver tenderness, yellowing of the skin (jaundice), buildup of fluid in the abdomen (ascites), and weight gain from fluid retention. Some chemotherapeutic agents like busulfan and cyclophosphamide are more likely to cause SOS. Certain treatments including ursodeoxycholic acid and defibrotide can be used to prevent or treat SOS.
Another rare but serious complication is Idiopathic pneumonia syndrome that happens within the first three months after a transplant. It is due to the damaging effect of the preparative treatment on lungs and is usually managed with steroids.
Sometimes the body can reject the new bone marrow (graft rejection or failure). This is more common when there is a significant disparity between the patient’s and donor’s immune system markers. Early identification of graft rejection or failure is crucial, usually done by looking for cells from the donor (chimerism). Studies have shown that effective chimerism can improve transplant success and survival rates.
Graft versus host disease (GVHD) is a condition where the donor’s immune cells attack the recipient’s body. This can be acute (happens soon after the transplant) or chronic (long-lasting). Severity is graded using the Glucksberg scale for acute GVHD and the National Institute of Health scale for chronic GVHD. Both types of GVHD are usually treated with steroids, though the treatment course for chronic GVHD is usually longer, potentially lasting over two years.
Finally, the treatments used to prepare for the transplant and suppress the immune system afterwards can lead to a severe decrease in all types of blood cells (pancytopenia) in the first week after the transplant. This is called toxicity and it can make patients more susceptible to infections and other complications.