Hematopoietic Stem Cell Therapy For Blood Disorders

Hematopoietic stem cell therapy (HSCT) is revolutionising the landscape of blood disorder treatment by utilising the abilities of naturally occurring body cells called stem cells. These cells are capable of transforming into different specialised cell types, which aids healing and rebuilding of tissues, as well as replacing dead cells. This therapy holds promise for patients facing conditions such as blood cancers, thalassemia, sickle cell disease and more.

Introduction  

Overview of Hematopoietic stem cells

Hematopoietic stem cells (HSCs) are cells mainly found in the blood and bone marrow that can divide and transform into different specialised blood cells, such as red blood cells RBCs) and white blood cells (also known as immune cells). These are vital for virtually all bodily processes, as RBCs are responsible for carrier oxygen and nutrients around the body, and immune cells protect against and fight infection. The regeneration of blood cells (hematopoiesis) is required to replace any dead or damaged cells, to allow them to continue functioning effectively. 

Blood disorders¹

Blood is composed of red blood cells, white blood cells, and platelets. There are over 5000 diseases linked to mutations in genes that affect these cells, particularly their ability to function properly of the number of them present in the blood. Most of these mutations specifically affect HSCs or the cells that are produced as a result of HSC division. This leads to defects in the formation of new blood cells or specific issues in the function of the new cells.

Stem cell therapy 

Hematopoietic stem cell transplant (commonly referred to as bone marrow transplant, although this isn’t the only type of stem cell therapy) involves harvesting functional HSCs and implanting them in patients with blood disorders. These new, healthy cells can then divide and replace the dysfunctional cells, either treating or effectively curing many disorders. There are a variety of different types of transplants from many sources, the best course of action is decided based on the type of disorder and the needs of the patient.

Types of transplant²

Syngeneic 

This is where the donor and recipient are identical twins.

It’s useful as there is no risk of the graft failing due to incompatibility between the host and donor cells (known as rejection or graft versus host disease - discussed in the complications section). However, the patient will rarely have an identical twin, other transplant methods are usually needed.

Autologous 

This is where healthy stem cells are collected from the patient, purified, and then reinserted to replace damaged or defective bone marrow cells.

This is particularly useful for patients who undergo chemo and radiation therapies which will likely cause damage to their stem cells, such as lymphoma. These patients will have a slightly different preparation routine, including medication which will increase the development of stem cells ready for collection. In this case, there is also no need to worry about graft vs host disease as these are the patient's own cells. 

However, there is a higher risk of relapse as the reinfused cells may contain defective cells, which can quickly overpower the healthy cells. Patients will have low blood counts for an extended period, creating a greater risk of infection. As well as this, there needs to be healthy cells present, so in the case of many inherited disorders which affect all HSCs, this is not possible.³ 

Allogeneic 

This is where stem cells from a HLA-matched donor are used to replace the recipient’s unhealthy cells. The donor can be anyone from a family member to a complete stranger.

Scientists will look at specific genes of the donor and recipient called human leukocyte antigens (HLA). These code proteins that help the body’s immune cells tell the difference between its cells and foreign material. This is important when it comes to fighting infections, so the body can tell when there’s something that shouldn’t be there, but it’s also particularly important in preventing graft rejection as if the HLA is matched, the body should recognise the new cells as being part of the body and therefore won’t attack them.⁴

This has a lower risk of relapse than autologous transplantation, however, the immune system has a harder time rebuilding after and there are more associated complications due to the strict preparative regime, which can cause organ damage and immunosuppression.⁴ 

Stem cell harvesting and implantation process

Harvesting⁵

Bone marrow transplant 

During a bone marrow transplant, the donor is given general anaesthetic, a needle is inserted into the pelvic bone, and the amount of bone marrow removed is decided by the concentration of stem cells. Usually, 0.5-1.5 litres are removed for the donation to contain enough cells. The cells are filtered from the bone marrow by scientists and prepared for infusion.  

The donor will spend a couple of days in hospital and will usually take a week or two off of work to recover. This process is more risky, due to the involvement of anaesthetic, but is still relatively safe. The donor may experience some temporary pain localised to the pelvis and back. 

Peripheral blood stem cell transplant 

This is a more modern method of stem cell transplant and involves filtering stem cells directly from the blood. The blood is less concentrated with stem cells than the bone marrow, so donors must be injected with a drug called granulocyte colony-stimulating factor (GCSF) beforehand which will cause stem cells to move into the bloodstream from the bone marrow.

Cells are harvested through a tube inserted into the arm and move through an apheresis machine which filters the blood. The filtered blood is reinserted into the donor’s other arm. This is an outpatient procedure but may need to be repeated in order to collect enough stem cells.

This is a much safer procedure due to the lack of anaesthetic, however, there is still some mild joint and bone pain associated with the growth factor drug.

Umbilical cord blood

Blood can be harvested directly from the umbilical cord after birth, and donated either to an anonymous public blood bank, or private blood banks to then be used if that child needs it in the future. 

Umbilical cord blood stem cells are currently only transplanted into other people, and it is unlikely that the newborn will see any benefit from privately storing their stem cells, as most childhood cancers are not treatable by autologous transplant. 

HSCs from the umbilical cord have a greater ability to differentiate into different cell types, making this a very effective source for transplantation. 

Transplantation²

Preparation 

A combination of chemotherapy and radiation is often given to destroy existing bone marrow and cancer cells, as well as suppressing the immune system to prepare for the new cells to be transplanted. 

There are two types of preparative regimes:

• Myeloablative⁷
• Reduced intensity⁸

The latter is preferred for older patients or those with a prior history of chemo and radiotherapy. This is associated with less organ damage and is better tolerated, however the relapse rates are higher due to remaining host cells.  

Preparation will immediately precede the transplant, and the host bone marrow should be effectively suppressed within 1-3 weeks. 

In the case of severe combined immunodeficiency (SCID), no preparation is needed as the body is already severely lacking immune cells, which is also beneficial in preventing graft rejection.²

Transplant 

Stem cells are inserted into the patient through a central line in the chest. This is painless and done without general anaesthetic. 

After the transplant, the patient will remain in hospital, usually for 1-3 months, in case of infection and to allow the new cells to start replacing the lost blood cells. There may be a lot of side effects experienced during this time, such as feeling weak, vomiting, and malnutrition. There is also a severe risk of infection during this time, so proper measures should be taken by the hospital and any visitors to mitigate this risk.  

Diseases that have been treated by HSCT

Many disorders have been successfully treated using hematopoietic stem cell transplantation. This includes blood disorders such as:

• Acute leukaemia 
• Severe aplastic anaemia 
• B-thalassemia major 
• Sickle cell disease
• Lymphoma 
• Immune deficiency disorders
• Multiple myeloma

Associated complications⁶

Graft versus host disease (GvHD)

The main risk associated with transplantation is graft versus host disease (GvHD). This is when the donor cells are unable to recognise the patient's cells as being safe and launch an immune response against them. This can occur anywhere from weeks to years post-transplant, and is the main reason many recipients of HSCT have to be on a strict regimen of immunosuppressants.  

Symptoms include:

• A dry, itchy rash
• Diarrhoea
• Shortness of breath
• Jaundice 
• Joint and bone pain 

Reduced number of blood cells

After the recipient’s stem cells are destroyed in preparation for transplant, it can take upwards of several weeks for the new cells to replace these. As a result, they are left with a much reduced number of blood cells. This increases the risk of several issues including: 

• Iron deficiency anaemia due to a lack of red blood cells 
• Excessive bleeding and bruising due to a lack of platelets
• Infections due to a lack of immune cells 

It is important to take precautions to avoid injury and infections until the body has had time to regenerate new blood cells.

Chemotherapy²

There are also many risks associated with the toxicity of the chemotherapy used in preparation of the transplant. These include:

• Sinusoidal obstruction syndrome (SOS)
• Idiopathic pneumonia syndrome (IPS)
• Pancytopenia

Summary 

The transplantation of hematopoietic stem cells has been revolutionary in the treatment of blood-based disorders. There are many different types of transplants coming from different sources, all of which have their benefits and associated risks. Patients undergoing transplant will have an increased risk of infection and may have to be on immunosuppressants indefinitely to prevent rejection of the transplant. 

Further resources 

• Anthony Nolan 
• Blood cancer UK 
• The national blood service 
• DKMS (delete blood cancer)

Isla Cogle

BSc Immunology student, University of Glasgow

Isla is an immunology student passionate about making science accessible to everyone. With years of experience as a science tutor and volunteer, she simplifies complex concepts and connects the public to current issues in medicine. Her dedication to education and medical communication drives her efforts to bridge the gap between research and public understanding, helping others to make informed decisions about their own health.

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