Every living organism consists of cells. Cells act as the instruction tool to the body. Even though they cannot be seen with the naked eye, they are crucial to every biological system, carrying essential instructions to build and maintain the body. They are constantly working, from fighting infections to repairing tissues to transporting materials internally from one organ to another. It has been estimated that the body accounts for about 30-36 trillion cells in the body.¹ Sometimes problems with cells can lead to a serious disease. One of which is abnormal cell growth, causing the world's most serious disease, cancer. 

What is Lymphoma 

Lymphoma is a type of blood cancer that affects white blood cells, which play a crucial role in the immune system. Lymphoma involves the lymph nodes. Lymph nodes play a vital role in fighting off infections. They are found all around the body, including the neck, armpits and groin. 

Lymphoma involves the abnormal growth of lymph nodes. The cells start to build up in the lymph nodes and sometimes spread to other parts of the body. There are two types of Lymphoma:

1. Hodgkin lymphoma (HL): A less common cancer, about 10% of lymphoma cases, with the highest cure rate of all human cancers^2,3
2. Non-Hodgkin lymphoma (NHL): The more common type of lymphoma, about 90% of cases, is clinically more aggressive²

Lymphoma treatment

Treatments are normally chosen by a team of healthcare professionals depending on the stage and type of lymphoma. The type of cells involved and cancer growth rate are considered by the healthcare team. There are multiple therapeutic options available for patients diagnosed with lymphoma:• Chemotherapy

• Radiotherapy
• Targeted therapy
• Immunotherapy
• Bone marrow transplant

The first line and most common treatment for lymphoma is chemotherapy. It is very promising and successful in cancer treatment. However, though chemotherapy targets cancer cells, it also destroys healthy cells. 

Stem cell transplant for lymphoma 

Stem cells

Stem cells are special cells mostly found in our bone marrow.⁴ Bone marrow is a tissue in the centre of most bones; a large number of the stem cells are found in the pelvic (hip) bone. While stem cells are also found in our blood, they are far less abundant than in the bone marrow. 

Stem cells are cells that have not yet developed or specialised into a specific type of cell. They can become any type of cell in the body and multiply into specific cells.⁴ They can also replace ageing and damaged cells. 

Stem cell transplant

Stem cell transplant is a medical treatment that involves replacing damaged or destroyed cells. A stem cell transplant will help the body produce new healthy cells after the high-dose cancer therapy. Although it is not a method that directly treats or fights the disease, it is essential for a speedy, healthy recovery. There are two types of stem cell transplant: autologous (own cells) and allogenic (donor cells). 

• Autologous stem cell transplantation is when the patient’s own stem cells are collected, stored and later reintroduced into their own body
• Allogenic stem cell transplantation is when stem cells are taken from a healthy donor. This would either be a family member or from the national registry

Even though patients with lymphoma have an increased disease-free survival, approximately 30% of patients experience relapse, in which the cancer returns after a period of remission.³ In this case, stem cell transplantation would be the standard case.⁵ Patients' own cells are normally used at first relapse. The donor’s bone marrow is often used in more advanced, aggressive cases because the stem cells are free of contamination by abnormal cells.⁶

Donor selection

For a donor to be selected, several factors must be considered: 

• Patients’ type of lymphoma
• Patients’ disease state and individual circumstances
• Urgency in obtaining a donor
• Human leukocyte antigen (HLA) tissue typing

There are about 43 million donors registered worldwide.⁷

Human leukocyte antigen system

If a patient's HLA does not match any family members, a donor who best matches the patient’s HLA would be chosen. The HLA system is a group of genes located on chromosome 6 that are expressed on the surface of white blood cells (leukocytes).⁸ HLA molecules are known to be highly variable between people. Testing HLA compatibility before a stem cell transplant is crucial since the body can reject the organ or blood transplant. This is why the HLA test is fundamental in stem cell transplant. The HLA system regulates the immune response.⁸ It works by helping the immune system respond to unknown and foreign cells entering the body, which in turn will help in fighting infections.

When undergoing a bone marrow and stem cell transplant, it is important to have an HLA typing test to confirm HLA compatibility, thus reducing complications such as graft-versus-host disease (GVHD).^8,9 This is when the donor’s immune cells start to attack the host’s cells, resulting in poor overall survival. 

Stem cell transplant process

If the donor’s HLA is compatible with the patient's, then the treatment may proceed to the next steps. Once the match has been confirmed, other factors must be considered, such as blood type. 

1. Harvesting - Collecting stem cells from the patient or a donor
2. Conditioning - Patients treated with chemotherapy and/or radiotherapy before cell transplant
3. Transplanting - The collected stem cells from the patient’s or donor’s blood are infused into patients’ bloodstream 
4. Recovery - Stem cells travel to the bone marrow

Harvesting

• Stem cells are collected from the bone marrow (Hip bone) using a needle
• Cells are stored in a blood bag and frozen until needed

Conditioning 

• Patients are treated with chemotherapy or combined chemotherapy and radiotherapy before stem cell transfusion¹⁰ 
• This will help by suppressing and weakening the immune system to prevent the body from rejecting the cells. It also destroys all cancer cells
• This process takes about a week or two⁹

Transplanting

• The stem cells collected are then infused into the patient’s bloodstream through a blood transfusion¹¹
• The stem cells start to move to the patient’s bone marrow, where they start to differentiate into healthy mature cells
• This process will take about 3-6 weeks⁹

Recovery

• Recovery takes about 2-3 months 
• Regular blood transfusions might be needed due to the low blood cell count
• The patient needs to stay in a special, germ-free room to avoid infections due to the weak immune system⁹
• Immunosuppressants are used to avoid immune system from attacking foreign cells (if donor cells are used)

Complications of allogenic stem cell transplant

Due to the weakened immune system from chemotherapy before the transplantation, there is a chance of developing complications such as infections, graft rejections, bleeding and fatigue. 

Epstein-Barr Virus

95% of humans have been infected with Epstein-Barr Virus (EBV), typically early in life.¹² Most people carry the virus without causing any harm to themselves. EBV infects white blood cells, specifically B-cells. When B-cells are infected with EBV, they begin to replicate and multiply.¹³ EBV plays a role in some lymphoma cases. It allows the infection to get out of hand due to a weak immune system. 

Graft-Versus-Host Disease 

GVHD occurs when a donor's stem cells react to the recipient’s cells and attack the host’s cells. It attacks the body’s organs, such as the gastrointestinal tract and the liver.⁹ GVHD could be acute (can happen 10 to 90 days after cell transplant), or chronic (happens after 100-400 days of stem cell transplant).⁹

Bleeding

Patients are at high risk of bleeding due to the low blood cell count in the first 3 weeks of treatment, at least.⁹ In case of a drop count in a blood cell, a blood transfusion is needed to help with recovery, since it takes about 3-6 weeks for the bone marrow to make blood cells after the stem cell transplantation.

Advantages of different stem cell transplantation 

• Allogenic: Donors’ cells are free of cancerous cells; they are not contaminated, which will reduce the chance of cancer relapse
• Autologous: Although the patient’s own stem cells could be contaminated, this type of transplantation minimises the chances of the patient’s body rejecting the stem cells as the body recognises the cells. There is also no risk of GVHD

Summary

Lymphoma is normally treated with chemotherapy, supported by stem cell transplantation. There are two types of transplantation: autologous, using the patient’s own stem cells, and allogenic, using donor cells with a compatible Human leukocyte antigen (HLA). A patient’s own cells are often safer to use as they have a lower risk of being rejected by the immune system. However, there is still a high chance of collecting contaminated samples with cancerous cells, even after chemotherapy, increasing the risk of relapse. In some cases, an allogenic stem cell transplant is usually recommended to achieve a higher success rate. However, the use of donors’ stem cells is associated with risks, such as infections and Graft-Versus-Host Disease (GVHD), in which the donors’ immune cells attack the patient’s body.