Introduction

If you’re experiencing aplastic anaemia, due to causes other than chemotherapy or pregnancy, you may suffer from prolonged fatigue and burden from treatments that may not be effective. Therefore, it is worth considering having stem cell transplantation if you’re eligible for it. 

Continue reading for a better understanding of the disease and stem cell transplantation, so you can be more knowledgeable when deciding on your treatment.

Aplastic anaemia

Simply put, aplastic anaemia is a rare condition in which insufficient blood cells are produced. This leads to a compromise in various functions normally carried out by the blood cells. To explain how stem cell transplantation works for aplastic anaemia, it is necessary to unravel what goes wrong.

What causes aplastic anaemia

Normal blood production process

Our body has stem cells, which can split into identical and more differentiated cells. Among them are haematopoietic (blood-producing) stem cells, which reside in the bone marrow, the spongy tissue inside our bones. Their division and differentiation lead to the production of our blood cells, including:

• Red blood cells: deliver oxygen from the lungs to respiring body cells that need energy to carry out normal functions
• Platelets: aggregate to clot our blood after injuries to stop blood loss and prevent infections
• White blood cells: carry out cell-eating, produce antibodies, and release toxins to eliminate pathogens (bacteria, viruses, etc.) from our body

What goes wrong in aplastic anaemia

There are many possible causes for aplastic anaemia, some of which are innate and most of which are acquired. Some rare and inherited diseases, that involve the failure of the bone marrow, can often lead to aplastic anaemia. Among them, the most common one is Fanconi Anaemia.¹ 

More often, the cause is due to certain life events, which is thus known as acquired aplastic anaemia. Most of them are caused by some immune events that lead to autoimmunity, in which the white blood cells produced by the stem cells attack those stem cells after reaching maturity. The exact causes of this autoimmunity are not completely known.² Some factors can directly damage the haematopoietic stem cells. These include certain chemicals, including benzene, a component of some gasoline. ³ Some cancer therapies, including chemotherapy and radiotherapy, can kill haematopoietic stem cells as a side effect of eliminating cancer cells. 

There are also known factors that use mechanisms, not completely clear, to damage the bone marrow, such as viral infections like hepatitis A and pregnancy.² In addition to these, there are cases where the cause cannot be easily identified, known as idiopathic aplastic anaemia.

Symptoms of aplastic anaemia

All three types of blood cells carry out vital functions. With all of them compromised, aplastic anaemia is associated with a wide range of symptoms:

• Reduced red blood cells: shortness of breath, irregular heartbeat, and fatigue
• Reduced platelets: bleeding nose and gums, frequent bruising, slow wound healing
• Reduced white blood cells: frequent and prolonged infections, fever

Treatments of aplastic anaemia

Various treatments are available to offset the effects of low blood cell counts. To address fatigue and blood clotting problems, blood transfusions can increase the amount of red blood cells and platelets in the blood to temporarily relieve these symptoms. For aplastic anaemia caused by autoimmunity, immunosuppressant medications may be used to reduce further damage to the haematopoietic stem cells. In cases of infections, due to low white blood cell count, antibiotics may be administered to prevent the infection from causing life-threatening effects. However, none of these treatments can provide a cure for aplastic anaemia. To potentially cure the disease, the bone marrow must have healthy, normally functioning haematopoietic stem cells, which can be transplanted from a donor and start producing blood cells in the long term.

How are stem cell transplants carried out?

Pre-transplant

Eligibility assessment

Factors including your age, overall health conditions, and the presence of other co-existing diseases are considered by your doctors when assessing whether you are eligible for a transplant. This is because you have to tolerate the side effects of the high-intensity conditioning therapy used before the transplant (which will be explained in more detail below). The type and severity of aplastic anaemia are also assessed to determine whether a transplantation is suitable and necessary. If all conditions are met, you can undergo a transplant as soon as a suitable donor is identified.

Donor matching and sources

Finding compatible stem cell sources can be difficult. For bone marrow transplant (BMT) for aplastic anaemia  (AA), there are two requirements: first, the donor must have healthy bone marrow, which produces functional blood cells; second, the donor’s white blood cell antigen profile (known as HLA) must match that of the recipient, otherwise, adverse immune responses can lead to unsuccessful of transplantation.

Close relatives, due to their genetic similarities with the patient, can easily meet the second requirement, having more willingness to donate. However, if the AA of the patient is inherited, close relatives are also more likely to have AA. If no close relatives can be donors, unrelated volunteers registered at stem cell banks are assessed for HLA compatibility and consent.

If no close relatives or compatible donors can be found, your doctor may also look into the cord blood bank. Parents of newborn babies may choose to donate their umbilical cord blood, which contains immature haematopoietic stem cells. 

Collecting stem cells

When a donor is identified, stem cells will be collected from either the bone marrow (via a needle inserted into the pelvic bone) or the peripheral blood (using apheresis, which filters out stem cells and returns the rest of the blood into the donor’s veins). Daunting as they sound, the site of bone marrow harvest will be anaesthetised and generally painless. If cord blood is used, the selected cord blood will be retrieved from the cord bank and thawed.

Conditioning therapy

Before transplantation, the remaining unhealthy stem cells in the bone marrow will be killed using high-dose chemotherapy or radiotherapy. This will leave the bone marrow empty so that new stem cells have space to reside and divide. This also stops the production of white blood cells that can attack the infused stem cells.

Due to the high intensity of the conditioning therapy, it is often associated with negative effects as other stem cells in the body are also affected. These include hair loss, nausea, and the symptoms of aplastic anaemia (the conditioning therapy induces a state of complete aplastic anaemia that facilitates the upcoming treatment).

Transplantation

The transplantation procedure is similar to a blood transfusion. Overall, a central line catheter is inserted from a major vein in the lower neck, upper chest, or groin all the way to the vena cava. The area of insertion is anaesthetised, and you will be awake throughout the procedure. The stem cells are infused into the blood flow, which will migrate to the empty bone marrow and populate it in a process known as engraftment.⁴

Risks of transplantation

While the surgeon will ensure maximum safety is achieved, the invasive nature of the procedure implies the possibility of certain risks. These are mainly accidental punctures into vital parts of the body (arteries, nerves, heart, and lungs).⁵ Due to the life-threatening potential of these accidents, you need to report any discomfort immediately to your surgeon, including swelling, unexplained pain, and difficulty breathing.

The invasive nature of the procedure implies that infection is a possible complication. Before engraftment, there are almost no functional white blood cells in your body, which means a common infection can become very serious. Therefore, you need to tell your consultants that you do not feel well, as this may be a sign of infection.

Outcomes of stem cell transplants

Graft-versus-host disease (GVHD)

Despite the effort during HLA matching, it is unlikely that stem cells from unrelated donors are perfectly compatible with the profile of the recipient. When healthy white blood cells are developed from the transplanted stem cells, they may recognise all the body cells as foreign and launch immune attacks. This may lead to inflammation throughout the body, with symptoms like diarrhoea, rashes, and shortness of breath. Because of the potential for being life-threatening, you may need to take immunosuppressive medications to suppress the newly developed immune system. 

The risk of serious GVHD is lower for people using cord blood for transplantation for reasons not completely known, and this fact has allowed many people without a compatible donor to have transplantation from imperfectly matching cord blood.⁶

Recovery and outlook

Engraftment typically takes a few weeks, and in most cases, GVHD is successfully managed. It was reported in 2023 that the five-year survival rate of aplastic anaemia patients treated with stem cell transplants was 75%.⁷ The three-year survival rates, also reported in 2023, range between 82% and 92%,  differing between different degrees of HLA matching and different ages.⁸ If fully recovered, you can have a much higher quality of life compared to other treatment plans.

Summary

Stem cell transplantation, despite its potential risks and complications, is the only cure for aplastic anaemia in many cases.. If advised so, it is worth considering the attempt to cure aplastic anaemia.