Introduction

Living with multiple myeloma can be painful and exhausting. Although a cure does not exist currently due to the cancerous nature of the disease, your quality of life can be hugely improved through a treatment known as stem cell transplantation. A better understanding of the disease and this treatment can help you make a better decision if you unfortunately have multiple myeloma.

Multiple myeloma

Multiple myeloma is a blood cancer that mainly involves the excessive production of a kind of white blood cell called plasma cells. Despite the lack of symptoms in its early stage, multiple myeloma can cause an array of symptoms in later stages, including bone pain, tiredness, digestive issues, and kidney problems. To understand the disease and its treatment, the normal blood production process and the abnormal one in the case of multiple myeloma should be explained first.

Normal blood production process

Stem cells are cells in our body that can divide into an identical stem cell and a more specialised cell. Certain stem cells located in the bone marrow, the spongy tissue within our bones, known as haematopoietic stem cells are responsible for the production of our blood cells, including:

• Red blood cells: transport oxygen from the lungs to body cells so that they can use the energy to carry out normal functions
• Platelets: clot our blood in case of injuries to prevent excessive blood loss and infections
• White blood cells: fight against pathogens (bacteria, viruses, etc.) infecting our body

What goes wrong in multiple myeloma?

Among white blood cells, B cells can become plasma cells when activated and produce antibodies. Antibodies play essential roles in fighting infections. In patients with multiple myeloma, certain B cells turn cancerous. That is, they experience certain genetic mutations that allow them to divide infinitely and produce a large number of plasma cells known as myeloma cells, and these myeloma cells produce non-functioning antibodies, known as M proteins.¹

How does this abnormality harm your body?

This overproduction of plasma cells and M proteins leads to a series of adverse symptoms and complications in various organs:

• Bones: Since the production of plasma cells takes place in the bone marrow, the excessive plasma cells harm your bones from within by mediating bone breakdown.² This results in bone pain and ease of fractures
• Digestive tract: Bone breakdown also leads to an increase in your blood calcium level, which subsequently causes constipation and nausea¹
• Blood: Healthy, vital haematopoietic stem cells are crowded out, and thus fewer normal blood cells are produced. The reduced red blood cell number compromises oxygen transport in your body and causes anaemic symptoms such as fatigue; the insufficient white blood cells make immune responses against pathogens slower and weaker¹
• Kidneys: The excessive M proteins are essentially useless and hard to degrade. Attempting to filter the M protein, kidneys can be damaged³

How to treat multiple myeloma

Treatments for multiple myeloma depend on the condition of each patient. For patients in the early stages of multiple myeloma, you may not need immediate treatments but need to monitor its progress with your consultant. For patients with severe symptoms and complications like bone pain and kidney damage, specific treatments such as painkillers and calcitonin may be necessary to tackle them.¹ In many cases, a stem cell transplant is suggested. It primarily involves chemotherapy that eliminates myeloma cells as much as possible and the re-infusing of haematopoietic stem cells to restore normal blood cell production once hampered by multiple myeloma and chemotherapy.^4,5 Getting to know how the whole process works allows you to make better decisions for your condition.

How do stem cell transplants work?

Types of stem cell transplants

Autologous transplant (patient’s own cells)

Because multiple myeloma is not a genetic disease and people with it have perfectly functional haematopoietic stem cells, their own stem cells can be transplanted back into their bone marrow for blood cell production after chemotherapy. This is known as an autologous transplant. It involves taking stem cells from the patient and injecting them back into the bone marrow. It is the default option because it does not need matching immune profiles and thus does not depend on the availability of a compatible donor and does not need to take precautions against adverse immune reactions.

Allogeneic transplant (donor cells)

In rare cases, an allogeneic transplant is used. It uses stem cells from an external source, known as a donor. The additional step of finding a donor is thus required. A suitable donor must have functional stem cells and matching immune profiles, which minimise undesirable immune reactions post-transplantation. However, this method means the collected stem cells are less likely to be contaminated by myeloma cells, which reduces the chance of relapse; the imperfectly compatible stem cells from the donor may also produce immune cells more capable of fighting against cancerous plasma cells⁶ Nonetheless, adverse immune reactions and other safety issues may still occur even when matching is achieved. (The graft-vs-host disease will be mentioned in more detail below.) Therefore, it is mostly limited to young patients with matching siblings and clinical trials.

How are stem cell transplants carried out?

Pre-transplant preparation

Eligibility assessment

Before any procedure is carried out, you would be checked for eligibility for stem cell transplantation. Your consultants will take many factors, including your age, stage of multiple myeloma, and other co-existing health conditions, into account.¹ There are no fixed eligibility criteria, so it is important to consult your doctors.

Induction therapy

Once you are considered eligible, you will go through induction therapy, which involves taking cycles of different medications targeting the myeloma cells for a few months. This aims to reduce the number of myeloma cells in your bone marrow so that the stem cells collected are less likely to be contaminated. ⁷

Collecting stem cells

After the induction therapy, your stem cells are collected from the peripheral blood. You would first take certain growth factors promoting the production of stem cells in your bone marrow and their mobilisation into the peripheral blood.⁸ In some cases, you may be given additional chemotherapy that stimulates the stem cells to migrate. This procedure normally lasts for several days. Afterwards, your stem cells would be harvested using the procedure of apheresis. This involves inserting a needle connected to a soft tube into the vein of each arm. One tube carries your blood into a machine that filters stem cells out and transports the remaining blood into another vein. The stem cells are collected and frozen to be transplanted.

Conditioning

A few days before the transplant, high-dose chemotherapy (often a drug called melphalan injected intravenously) or radiotherapy is used to eliminate any remaining myeloma cells to minimise the chance of relapse. Yet this also wipes out the healthy stem cells in the bone marrow. This then leaves the bone marrow almost “empty” so that the transplanted stem cells can proliferate without hindrance from cancer cells. Due to the potential of the therapy affecting other stem cells of the body, you may experience some unpleasant side effects like nausea and hair loss. Your doctor would provide you with the necessary medications to deal with these.

Transplant day

Once your bone marrow is “empty” and melphalan is cleared from the body (takes about 1-2 days), you are ready for the transplant. A central venous catheter would be placed from your neck, upper chest, or infrequently the groin to the major vein of your heart. Your stem cells will be thawed and infused into your blood. The place of catheter insertion would be anaesthetised, and you would be awake yet painless during the procedure.

Despite the great effort devoted to the safety of the procedure, complications may still occur and must be immediately addressed. When you feel or notice any swelling or numbness of the body and difficulty in breathing, inform your surgeon at once because there may be signs of punctures into your arteries, nerves, or lungs, which can be life-threatening. ⁹

What to expect after stem cell transplants

After the transplant procedure, you may need to have a hospital stay for a few weeks to monitor any adverse side effects and monitor the engraftment of your stem cells.

Risks and side effects

Infections

Since the procedure is invasive, infection may occur through the wound. ⁹ Since you have little haematopoietic stem cells around the period of transplant, your immune system is likely to be very weak, which means infections need to be taken seriously. Therefore, report any discomforts to your consultants as they can be signs of infection so that you can have medications tackled as soon as possible.

Graft-vs.-host disease (GVHD)

If an allogeneic transplant is used, GVHD may occur. It refers to the situation when immune cells developed from the donor’s stem cells recognise all cells of the body as foreign and attack them, resulting in symptoms throughout the body. Similarly, it can be life-threatening, so you would typically be administered immunosuppressants to prevent and control GVHD.

There are many other side effects due to the chemotherapy and the procedure, such as fatigue. Depending on the regimens used for each step, potential risks and side effects vary. Consult your doctors for a more exhaustive list of risks and side effects for your selected treatment, and pay attention to the advised precautions against certain activities.

Benefits and success rates

It typically takes a few weeks for the stem cells to successfully engraft—migrate into the bone marrow and start producing functional blood cells. ¹⁰ After this point, your body regains the functioning of blood cells. For example, the risk of infections decreases as new white blood cells are produced. The side effects of the chemotherapy would also start to improve.

The advent of stem cell transplants for multiple myeloma made the disease less incurable. According to data in the US until 2022, the three-year survival rate is 83% on average, and it is expected to rise as the treatment gradually improves.¹¹

To improve the outcome and extend the remission duration, further consolidation therapies and maintenance therapies with medications may be used. If relapse occurs, a second stem cell transplant may be recommended.

Summary

By wiping out cancerous myeloma cells and reintroducing stem cells back to the bone marrow, stem cell transplants allow multiple myeloma patients to have their cancer controlled while having normal blood functions. They result in massively improved outcomes compared to previous treatments, so you must discuss with your consultants whether to have a stem cell transplant.