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What is stem cell therapy?
Stem cell therapy, or stem cell transplant, is a procedure that aims to restore blood-forming stem cells in patients who have undergone chemotherapy or radiotherapy. The treatment helps to restore damaged blood cells such as red blood cells, white blood cells, and platelets.
Blood-forming stem cells are indispensable because they can grow into different blood cells – they are the body’s “building block” that can mature into any type of blood cell with specialised functions.
Autologous stem cell (patient’s own stem cells) transplant is used to help patients recover from the effects of chemotherapy.
Allogeneic stem cell (stem cells from a donor) transplant is used to help patients recover from the effects of chemotherapy and/or radiotherapy as well as to eradicate the remaining cancer cells in the patient after chemotherapy and/or radiotherapy.
How does this therapy work?
All of the blood cells in the body come from immature cells called hematopoietic stem cells, HSCs (hematopoietic means blood-forming). HSCs mostly stay in the bone marrow and mature into blood cells as they grow.
Bone marrow cancers such as multiple myeloma, leukaemia, and lymphoma, reduce the formation of HSCs in the bone marrow. Chemotherapy or radiotherapy used to treat these cancers will destroy the HSCs in the bone marrow and abolish the body’s ability to regenerate blood cells.
Stem cell transplant is often a part of the treatment plan for blood cancers. The patient first receives a high dose of chemotherapy and/ or radiotherapy to eliminate the remaining cancer cells in the body. This high-dose therapy will also destroy the HSCs in the bone marrow. The damaged bone marrow will then be replenished with new stem cells to alleviate the side effects of the high-dose therapy.
In allogeneic stem cell (stem cells from a donor) transplant, there is another benefit in addition to replenishing the HSCs in the bone marrow after chemotherapy or radiotherapy. It gives the patient a whole new and healthy immune system of the donor. The donor immune cells can kill the leftover cancer cells and will exert a “graft-versus-cancer” effect, keeping the cancer cells in check. These cells can self-renew and the patient can enjoy a long-term cure from blood cancer.
Receiving Stem Cell Therapy
Different types of stem cell therapy bring different benefits
Stem cells can be collected from different sources.
- Bone marrow stem cell transplant: Stem cells are collected from the bone marrow – the spongy soft tissues in the bones. Frequently, stem cells are taken from the pelvic bone, filtered, and stored under special conditions for future transplants.
- Peripheral blood stem cell transplant: A small number of stem cells can be found in the blood, and these can be collected for stem cell therapy. However, the number is often so low that growth factors are needed to increase the blood concentration of stem cells before a collection can be performed. Peripheral blood stem cells are the preferred source of HSCs because of the relative ease of collection. Additionally, patients do not need to undergo the bone marrow procedure under sedation.
- Cord blood transplant: The blood that is left behind in the placenta and umbilical cord after a baby is delivered contains stem cells, and these can be carefully collected and stored. The baby will not be harmed in any way during the cord blood collection.
Additionally, stem cell transplants can also be categorised based on who donates the stem cells. There are two main sources:
- Autologous (i.e. “self”) transplant: The stem cells originate from the patient who will receive the transplant.
- Allogeneic (i.e. “others”) transplant: A donor, either related or unrelated to the patient, who donates the stem cells for transplant.
Finding a suitable donor is key
Finding a donor with suitable stem cells is critical to avoid graft rejection or graft-versus-host syndrome. An unsuitable donor means the immune system of the recipient recognises the difference between “self” and “non-self” tissues, and will likely destroy the foreign “non-self’ tissues after a transplant.
Many factors dictate whether the donor stem cells are suitable for the recipient but the most important one is the human leukocyte antigen (HLA) system. These are specific proteins found on the surface of most cells, and the combination of HLA subtypes is passed down from parents to children.
A match between donor and recipient happens when all six of the known major HLA antigens are the same (a 6-out-of-6 match). Sometimes, a 5-out-of-6 match is used too.
Some doctors will use other high-resolution matching methods (such as a more comprehensive 10-out-of-10 match or 12-out-of-12-match) to further reduce the risks associated with stem cell transplants.
A search for a matched donor typically starts with the patient’s siblings since they would have inherited the combination of HLA from the same parents. If siblings are not a good match, the search will be expanded to other relatives or the general public. It is still possible to find a good match with a stranger.
With advances in stem cell transplant protocols, a donor who is half-HLA matched with the patient can also be a potential donor for the patient. In many circumstances, these donors are the patient’s relative: parent, child or sibling. This type of transplant is called a haploidentical transplant and it can successfully be done with similar outcomes compared to the transplant performed with full-HLA matched donors. Patients can, therefore, have a higher chance to undergo haematopoietic stem cell transplantation overcoming the barrier of full HLA matching.
Stem cell therapy success rate
It is difficult to calculate the overall success rate for stem cell therapy alone since almost all patients receive a combination of chemotherapy, radiotherapy, or immunotherapy with stem cell transplants.
However, recent data on certain blood cancers are highly encouraging. The transplant survival rates published by the U.S. Health Resources and Services Administration show that in 2021, 79% of patients with multiple myeloma were alive three years after transplant. For Hodgkin lymphoma, 92% of patients who received a transplant and underwent chemotherapy were alive after three years, while for Non-Hodgkin lymphoma, 72% were alive three years after diagnosis.
Benefits And Risks
Benefits of stem cell therapy
Cancer treatment has advanced greatly over the past decades. New chemotherapy or immunotherapy drugs are more effective, have fewer side effects, and significantly improve cancer survivorship.
However, most of these cancer drugs still have insufficient and non-specific tumour targets which result in suboptimal treatment. There is a possibility that resistance to these cancer drugs may occur, and cancer may relapse at a later date. Stem cell therapy provides a hopeful option for these cancer patients.
Risks of stem cell therapy
In an autologous (self) stem cell transplant, there is no risk that the body will reject the engrafted cells since these stem cells originate from the same person. However, there is a small chance that the graft may fail to enter the bone marrow to produce new blood cells.
It is also possible, albeit very rare, that cancer cells are harvested during stem cell collection and reintroduced into the body during a transplant. This is preventable as your transplant team will screen, process and remove these cancer cells via a process known as purging before the stem cells are transplanted.
When the stem cells are donated, there is a small chance that these will fail to settle in the bone marrow, or be rejected by the body (graft rejection).
Likewise, the donated stem cell may reject the recipient body too – a condition known as graft-versus-host disease. These conditions are well known by doctors who have extensive experience in managing them.
Managing stem cell therapy side effects
Like many other treatments for cancer, you need to closely monitor side effects after starting treatment. Some will appear soon after having chemotherapy and just before your transplant. Others will occur at a later stage.
It is essential to notify your cancer care team immediately if your health deteriorates or notice any changes to the side effects you expect from your treatment. Some of these changes may be serious and warrant immediate attention from your cancer care team.
We have outlined several common side effects, but you should keep in mind that this is not a complete list. You are encouraged to speak to your doctor if you wish to know more about the specific side effects of your treatment.
There are risks of infection when the bone marrow functions are reduced. Until the transplanted stem cells begin to produce enough white blood cells to defend your body, you may be given antibiotics to prevent bacterial infections.
There is also a possibility that “hidden” viral infections may become active again. When the immune system is healthy, it keeps these viruses in check but the disease will manifest again after the immune system is compromised. For example, the cytomegalovirus (CMV) commonly infects adults but does not cause any trouble when the immune system is functional. In transplanted patients with a low white blood cell count, CMV may cause lung infections.
Usually, it will take 6 to 12 months for the immune system to recover after a transplant. In patients with graft-versus-host disease, this may take longer. It is critical to closely monitor any signs or symptoms that could indicate an infection. These include having a fever, cough, shortness of breath, or diarrhoea.
You will likely be placed under strict infection-control measures during your stay in the hospital to protect your health. All visitors and healthcare personnel who enter your room must wear protective gowns, shoes covering, gloves and masks.
Moreover, your transplant team will inform you about the necessary precautions when you are discharged from the hospital. Often, these include avoiding contact with potential sources of infection such as soil and faeces. Sometimes your doctor may recommend moving the cat litter box away from the places you are most likely to spend your time if you or your family have a pet cat.
Graft-versus-host disease (GVHD)
GVHD happens when the transplanted cells reject the recipient's body. This can happen in allogeneic (“other”) transplants. When this happens, the skin, mouth, joints, gastrointestinal tract and liver are more likely to be impacted.
About one-third to one-half of patients who received an allogeneic transplant are expected to develop acute GVHD (within 90 days). Your doctor is most likely to have anticipated this and will prescribe certain medications, such as steroids or methotrexate, to prevent acute GVHD.
Chronic GVHD may start about 90 days after stem cell therapy. Immunosuppressants are used to treat the condition.
Other side effects
Nausea and vomiting may happen during chemotherapy that precedes a transplant. Doctors will prescribe some anti-nausea medications to prevent these, but you should understand that no single drug can completely control chemotherapy-induced nausea and vomiting. You may need to monitor your symptoms and let your doctor know if the medications are not working.
Additionally, there is a chance of bleeding as the treatment reduces bone marrows that produce platelets – specialised blood cells that help the blood clot. You will need to follow instructions to avoid injury and bleeding while waiting for the transplanted stem cell to replenish your platelet level.
Sometimes, you may need a blood transfusion if your red blood cell count becomes too low.
Frequently Asked Questions (FAQ)
Cancer stem cells are a small number of cells inside a tumour that possesses the unique characteristics associated with normal stem cell, especially in the ability to mature into different specialised cells. Cancer stem cells are also tumour-forming (tumorigenic). They can generate tumours through the process of self-renewal and maturation, and have been thought of as a driver for cancer growth.
Stem cell therapy is no more painful than the procedures required to collect or administer the cells. Many factors influence whether an injection (to collect or administer) is uncomfortable or not. The collection of the bone marrow is performed under anaesthesia where the patient is put under deep sleep and will not feel pain during the process.
Stem cells used for cancer therapy either come from the patient or a suitable donor. Sometimes, stem cells collected from the umbilical cord or placenta will be used too (the process does not harm the baby). Currently, no stem cells from the embryo (embryonic stem cells) are used for treatment.