About Lymphoma

Allogeneic stem cell transplant

An allogeneic stem cell transplant is an intensive treatment where you receive a transplant of donor (someone else’s) stem cells. This is different to when a patient receives their own cells back, which is called an autologous stem cell transplant. This is discussed on another page.

On this page:

Transplants in lymphoma fact sheet

Allogeneic Transplants in lymphoma fact sheet

Overview of allogeneic stem cell transplants?

Dr Amit Khot, Haematologist & bone marrow transplant physician
Peter MacCallum Cancer Centre & Royal Melbourne Hospital

Allogeneic stem cell transplantation uses stem cells collected from a donor (someone else) to replace your own stem cells. This is done to treat Lymphoma that is refractory (not responding to treatment) or relapsing (lymphoma that keeps coming back. Most people with lymphoma do not need a stem cell transplant. In lymphoma, allogeneic (donor) transplants are much rarer than autologous (self) transplants.

Lymphoma is a cancer of lymphocytes. Lymphocytes are a type of white blood cell that develops from stem cells. The goal of chemotherapy is to eradicate the lymphoma cells and all the stem cells which could potentially grow up into lymphoma. Once the bad cells are eradicated, new cells can grow back which are hopefully not cancerous.

In the case of people who have relapsed or refractory lymphoma, this is not working – more lymphoma keeps growing despite the treatment. Therefore, eradicating the stem cells with very high doses of chemotherapy, then replacing that person’s stem cells with someone else’s can result in a new immune system where the donor stem cells take over the role of producing blood cells that don’t turn into lymphoma.

The aim of a stem cell transplant

There are a number of reasons why lymphoma patients may need a stem cell transplant that include:

  1. To treat lymphoma patients who are in remission, but they have a ‘high risk’ of their lymphoma returning
  2. The lymphoma has come back after initial standard first-line treatment, so more intense (stronger) chemotherapy is used to get them back into remission (no detectable disease)
  3. The lymphoma is refractory (has not completely responded) to standard first-line treatment with the aim to achieve a remission

The allogeneic stem cell transplant may provide two functions

  1. The very high doses of chemotherapy eliminate the lymphoma and the new donor cells provide a way for the immune system to recover, reducing the time that the immune system is out of action. The new donor cells take over the role of the immune systems function and production of healthy blood cells, such as lymphocytes. The donor stem cells replace the dysfunctional stem cells of the patient.
  2. Graft versus lymphoma effect. This is when the donor stem cells (called the graft) recognise any remaining lymphoma cells and attack them, destroying the lymphoma. This is a positive effect where the donor stem cells are helping to treat the lymphoma. It is important to note that this graft versus lymphoma effect does not always happen like this. The lymphoma can be resistant to the donor stem cells, or the recipient’s body (called the host) can fight against the donor cells (called the graft) resulting in graft versus host disease (a complication of allogeneic transplant).

The process of an allogeneic stem cell transplant has five stages

Dr Amit Khot, Haematologist & bone marrow transplant physician
Peter MacCallum Cancer Centre & Royal Melbourne Hospital

  1. Preparation: this includes blood tests to determine the type of cells you require. Sometimes people need to have ‘salvage’ chemotherapy to try and minimise the lymphoma before transplant.
  2. Stem cell collection: this is the process of harvesting stem cells, because an allogenic transplant is from a donor, the medical team needs to find a match for the transplant.
  3. Conditioning treatment: this is the chemotherapy, target therapy and immunotherapy that is administered in very high doses to eliminate all of the lymphoma
  4. Reinfusion of stem cells: once the high dose treatments have been administered, the stem cells which were previously collected from the donor, are administered.
  5. Engraftment: this is the process by which the donor stem cells settle into the body and take over the functioning of the immune system.

Preparation for treatment

There will be a lot of preparation required in the lead up to a stem cell transplant. Every transplant is different and the transplant team should organise everything for the patient. Some of the preparations to expect can include:

The insertion of a central line

If the patient does not already have a central line, then one will be inserted before the transplant. A central line can be either a PICC (peripherally inserted central catheter). It could be a CVL (central venous line). The doctor will decide what central line is best for the patient.

The central line provides a way to receive many different medications at the same time. Patients generally need lots of different medications and blood tests during transplant and a central line helps the nurses better manage the care of the patient.

For more info see
Central Venous Access Devices

Chemotherapy

High dose chemotherapy is always administered as part of the transplantation process. The high dose chemotherapy is called conditioning therapy. Outside of the high dose chemotherapy, some patients need salvage chemotherapy. Salvage therapy is when the lymphoma is aggressive and needs to be reduced before the rest of the transplant process can go ahead. The name salvage comes from trying to salvage the body from the lymphoma.

Relocation for treatment

Only certain hospitals within Australia are able to carry out allogeneic stem cell transplantation. Because of this, may need to relocate from their home, to an area closer to the hospital. Most transplant hospitals have patient accommodation that the patient and a carer can live in. Speak to the social worker at your treatment centre to find out about accommodation options.

Fertility preservation

Stem cell transplantation will impact upon the patient’s ability to have children. It is important that options that are available to preserve fertility are discussed.

Practical tips

Having a stem cell transplant usually involves a long hospital stay. It might be helpful to pack some of these things:

  • Several pairs of soft, comfortable clothes or pyjamas and plenty of underwear.
  • Toothbrush (soft), toothpaste, soap, gentle moisturiser, gentle deodorant
  • Your own pillow (hot wash your pillowcase and any personal blankets/throw rugs before hospital admission – hot wash them to reduce bacteria as your immune system will be very vulnerable).
  • Slippers or comfortable shoes and plenty of pairs of socks
  • Personal items to brighten up your hospital room (a photo of your loved ones)
  • Entertainment items like books, magazines, crosswords, iPad/laptop/tablet. The hospital can be very boring if you don’t have anything to do.
  • A calendar to keep track of the date, long hospital admissions can blur all the days together.

HLA and Tissue Typing

When having an allogeneic (donor) stem cell transplant, the transplant coordinator organises a search for a suitable stem cell donor. An allogeneic stem cell transplant is most likely to be successful if the donor’s cells closely match the patient. To check this, the patient will have a blood test done called tissue typing that looks at different proteins on the surface of the cells called human leukocyte antigens (HLA).

Everybody’s cells make HLA proteins to help the immune system recognise cells that belong in the body and recognise cells that do not belong.

There are lots of different types of HLA and the medical team tries to find a donor whose HLA types match own as closely as possible.

If possible, they also try to make sure the patient and the donor have been exposed to the same viruses, although this is less important than HLA-matching.

Brothers or sisters are most likely to have HLA proteins that are similar to the patient. Around 1 in 3 people have a brother or sister who is a good match. If a patient doesn’t have any brothers or sisters, or if they are not a good match, the medical team will search for a volunteer donor whose HLA type matches the patients as closely as possible. This is known as a matched unrelated donor (MUD) and millions of volunteers are registered with the national and global stem cell registries.

If a matched unrelated donor (MUD) is not found for the patient, it might be possible to use other sources of stem cells. These include:

  • A relative whose HLA type half matches yours: this is known as a ‘haploidentical’ donor
  • Umbilical cord blood from an unrelated donor: umbilical cord blood does not have to be as closely matched to your HLA type as other sources of stem cells. It is more likely to be used for children than adults because it contains fewer stem cells than other sources. Registers of stored umbilical cord blood are available.

Collection of Stem Cells

There are two ways a donor can donate stem cells.

  • Peripheral blood stem cell collection
  • Bone marrow blood stem cell donation

Peripheral blood stem cell donation

Peripheral stem cells are collected from the peripheral blood stream. In the lead up to peripheral stem cell collection, most people receive injections of growth factor. Growth factors stimulate stem cell production. This helps stem cells move from the bone marrow, into the bloodstream, ready for collection.

The collection happens by separating stem cells from the rest of the blood and the process uses an apheresis machine. An apheresis machine can separate different components of the blood and can separate out the stem cells. Once the blood has travelled through the cell collection phase it travels back into the body. This process takes several hours (roughly 2 – 4 hours). The donor can go home after the procedure, however, may need to return the next day if not enough cells were collected.

Apheresis is less invasive than bone marrow collection and this is partly why it is the preferred method of stem cell collection.

In allogeneic (donor) transplants, the donor undergoes apheresis for the recipient and this collection takes place as close to the day of transplant as possible. Because these stem cells will get delivered fresh to the recipient on the day of transplant.

Bone Marrow blood stem cell donation

The less common approach to collecting stem cells is a bone marrow harvest. This is where the stem cells are withdrawn from the bone marrow under general anaesthesia. Doctors insert a needle into a bone in the pelvic region, called the iliac crest. The bone marrow is withdrawn from the pelvis, through the needle and this bone marrow is then filtered and stored until the day of the transplant.

Cord blood donation is from the public cord bank where a donation of stem cells from the blood left behind in the umbilical cord and placenta after a baby is born has been donated and stored.

How apheresis works

Processing/preserving the stem cells or bone marrow

Stem cells collected for allogeneic (donor) transplant, are collected immediately before use and not stored for any length of time.

Stem cells collected for autologous (self) transplant, are generally preserved and stored in a freezer until ready for use.

Conditioning

Patients undergoing a transplant are first given treatment termed the conditioning regimen. This is high-dose treatment administered in the days before the stem cells are infused. Conditioning therapy can include chemotherapy and sometimes radiation therapy. The two goals of conditioning therapy are:

  1. To kill as much lymphoma as possible
  2. Reduce stem cell population

 

There are many different combinations of chemotherapy, radiation therapy and immunotherapy that can be used in conditioning regimes. There are different intensities of conditioning treatment, they are:

  • Full intensity myeloablative conditioning
  • Non myeloablative conditioning
  • Reduced intensity conditioning

 

In all regimens the treatment is intensive and as a result, a lot of healthy cells die along with the lymphoma. The choice of regimen will depend on the type of lymphoma, treatment history and other individual factors such as age, general health and fitness. The treating team will discuss with the patient which conditioning regimen is appropriate for the patient.


In an allogeneic transplant, patients can be admitted to hospital as early as 14 days prior to the transplant. Each patients case is different and your doctor will inform you of when you’ll be admitted. Patients remain in hospital anywhere from 3 – 6 weeks post transplant. This is a guideline; every transplant is different, and some people need more medical care for longer than 6 weeks.

If you are having an allogeneic stem cell transplant using stem cells from an unrelated or major mismatched donor, you may need higher intensity conditioning treatment.

You might have different conditioning treatment if you are having an allogeneic transplant using stem cells from umbilical cord blood or from a half-matched relative.

You can access detailed information on conditioning regimens on the Eviq website.

Reinfusing stem cells

After the intensive conditioning chemotherapy has finished, the stem cells are reinfused. These stem cells slowly begin to produce new, healthy blood cells. Eventually, they will produce enough healthy cells to repopulate the whole bone marrow, replenishing all blood and immune cells.

Having the stem cells reinfused is a straightforward procedure. It is similar to a blood transfusion. The cells are given through a line into the central line. The day the stem cells are reinfused is referred to as “Day Zero”.

With any medical procedure, there is a risk of having a reaction to the stem cell infusion. For most people there is no reaction, but others might experience:

  • Feeling sick or being sick
  • Bad taste or burning feeling in your mouth
  • High blood pressure
  • Allergic reaction
  • Infection

 

In allogeneic stem cell transplants, as these donated cells take hold (or engraft) in the recipient (patient). They begin to function as part of the immune system and may attack the lymphoma cells. This is termed graft-versus lymphoma effect.

In some cases, following allogeneic transplant, the donor cells also attack the patient’s healthy cells. This is called graft-versus-host disease (GVHD).

Engraftment of your stem cells

Engraftment is when the new stem cells begin to gradually take over as the primary stem cells. This generally happens around 2 – 3 weeks after the infusion of stem cells but can take longer, especially if the new stem cells have come from umbilical cord blood.

While the new stem cells engraft, you are at a very high risk of getting an infection. People generally have to remain in hospital for this period, because they can get sick and need to be able to receive treatment right away.

While you are waiting for your blood counts to improve, you might have some of the following treatments to support your recovery:

  • Blood transfusions – for low red blood cell count (anaemia)
  • Platelet transfusions – for low platelet levels (thrombocytopenia)
  • Antibiotics – for bacterial infections
  • Antiviral medication – for viral infections
  • Anti-fungal medication – for fungal infections

Engraftment syndrome

After receiving the new stem cells, some people develop the following symptoms 2-3 weeks later, generally around the time of cell engraftment:

  • Fever: high temperature of 38 degrees or above
  • A red rash
  • Diarrhoea
  • Fluid retention

This is called ‘engraftment syndrome’. It is more common after a self (autologous) stem cell transplant than a donor (allogeneic) stem cell transplant.

It is a common side effect of transplant and is treated with steroids. These symptoms can also be caused by other factors, including chemotherapy, and might not be a sign of engraftment syndrome.

Some common hospital protocols during a transplant include:

  • You usually stay in a hospital room on your own for the duration of your stay
  • The hospital room is cleaned regularly and sheets and pillowcases are changed every day
  • You cannot have live plants or flowers in your room
  • Hospital staff and visitors must wash their hands before entering your room
  • Sometimes visitors and hospital staff might need to wear gloves, gowns or aprons, and face masks when visiting you
    People should not visit you if they are unwell
  • Children under a certain age might not be allowed to visit at all – although some hospitals allow them to if the children are well

 

Once your blood counts have recovered and the patient is well enough, they can go home. After this time, they will be followed-up closely by the medical team.

Complications from stem cell transplantation

Graft Versus Host Disease (GvHD)

Graft-versus-host disease (GvHD) is a common complication of an allogeneic stem cell transplant. It happens when:

  • The donor T-cells (also termed the ‘graft’) recognises antigens on other cells in the recipient’s body (called the ‘host’) as foreign
  • After recognising these antigens, the donor T-cells then attack the cells of their new host.

 

This effect can be useful when the new donor T-cells attack the remaining lymphoma cells (called the graft versus lymphoma effect). Unfortunately, the donor T-cells can also attack healthy tissues. This can cause serious side effects.

Most of the time GvHD causes mild-to-moderate symptoms, but occasionally, it can be severe and even life-threatening. Before and after the transplant, patients are given treatment to reduce the risk of developing GvHD. The transplant team monitors the patient closely for any signs of GvHD so they can treat it as early as possible, if it develops.
GvHD is classed as ‘acute’ or ‘chronic’ depending on the signs and symptoms.

Risk of Infection

Following a stem cell transplant, the high doses of chemotherapy will have eliminated a lot of white blood cells, including a white blood cell called neutrophils. A low level of neutrophils is known as neutropenia. Prolonged neutropenia puts someone at a very high risk of developing an infection. The infections can be treated, however if not caught early and treated immediately they can be life-threatening.

While in hospital, immediately after the stem cell transplant, the treating team will be taking precautions to prevent infections developing as well as closely monitoring for signs of infection. Although many precautions are taken to reduce the risk of contracting an infection, most patients who have an allogeneic stem cell transplant will get an infection.

In the first few weeks after the transplant, patients are at the highest risk of developing a bacterial infection. Such infections include, bloodstream infections, pneumonia, digestive system infections or skin infections.

In the next few months, patients are most at risk of developing viral infections and these might be viruses that were lying dormant in the body before the transplant and may flare up when the immune system is low. They do not always cause symptoms. Regular blood tests after the transplant will be done to make sure a flare-up of a viral infection called cytomegalovirus (CMV) is detected early. If a blood tests shows CMV is present – even if without symptoms – the patient will have treatment with antiviral drugs. More than one course of treatment may be needed and this treatment could prolong the hospital stay.

Blood counts start to rise between 2 to 4 weeks after an allogeneic stem cell transplant. However, it can take many months, or sometimes even years, for the immune system to recover fully.

When being discharged from the hospital the medical team should advise what signs of infection to look out for and who to contact if there is a possible infection or anything else that may be a worry for the patient.

Side effects of very high dose chemotherapy

Patients are likely to experience side effects from the high-dose anti-cancer treatment. The following side effects may be common and more information is in the side effects section

  • Oral Mucositis (sore mouth)
  • Anaemia (low red cell count)
  • Thrombocytopenia (low platelet count)
  • Nausea and vomiting
  • Digestive tract problems (diarrhoea or constipation)

Graft failure

Graft failure occurs if the transplanted stem cells fail to settle in the bone marrow and make new blood cells. This means the blood counts do not recover, or they begin to recover but then go down again.

Graft failure is serious but it is rare after an allogeneic stem cell transplant, especially if the donor is a good match.

The medical team will monitor blood counts closely and if the new stem cell begins to fail, the patient might be treated initially with growth factor hormones. These can encourage the stem cells in the bone marrow to produce more cells.

If the donor stem cells do not engraft, the patient might need a second stem cell transplant. This second transplant can be either from the same stem cell donor or a different one.

Late effects

Late effects are health problems that may develop months or years after the lymphoma treatment. Most transplant centres have dedicated late effects services that offer screening programmes to detect late effects as early as possible. This gives the patient the best chance of being treated successfully if they develop any late effects.

Patients may also be at risk of developing Post-Transplant Lymphoproliferative Disorder (PTLD) – lymphomas that can develop in people who are taking immunosuppressant drugs after a transplant. However, PTLD is rare. Most patients who have had transplants do not develop PTLD.

For more info see
Late Effects

Follow-up care

After a stem cell transplant, there will have regular (weekly) appointments with the doctor. Follow up will continue for months and years after treatment, but less and less frequently as time passes. Eventually the transplant doctors will be able to hand over the follow up care, to the patients GP.

Approximately 3 months after a transplant, a PET scan, CT scan and/or bone marrow aspirate (BMA) may be scheduled to assess how the recovery is going.

It is common to have to go back into hospital for treatment in the weeks and months that follow a transplant but as time goes on, the risk of serious complications decreases.

Patients are also likely to be experiencing side effects from the high-dose treatment and may feel unwell and very tired. However, it usually takes around a year to recover from a stem cell transplant.

THE medical team should advise on other factors to consider during the recovery period. Lymphoma Australia has an online private Facebook page, Lymphoma Down Under where you can ask questions and get support from other people affected by lymphoma or a stem cell transplant.

What happens after a stem cell transplant?

Finishing treatment can be a challenging time for many patients, as they readjust back into life after transplant. Some of the common concerns can be related to:

  • Physical
  • Mental wellbeing
  • Emotional health
  • Relationships
  • Work, study and social activities
For more info see
Finishing Treatment

Further Information

Steve was diagnosed with mantle cell lymphoma in 2010. Steve has survived both an autologous and an allogeneic stem cell transplant. This is Steve’s story.

Dr Nada Hamad, Haematologist & bone marrow transplant physician
St Vincent’s Hospital, Sydney

Dr Amit Khot, Haematologist & bone marrow transplant physician
Peter MacCallum Cancer Centre & Royal Melbourne Hospital

Dr Amit Khot, Haematologist & bone marrow transplant physician
Peter MacCallum Cancer Centre & Royal Melbourne Hospital

Dr Amit Khot, Haematologist & bone marrow transplant physician
Peter MacCallum Cancer Centre & Royal Melbourne Hospital

Dr Amit Khot, Haematologist & bone marrow transplant physician
Peter MacCallum Cancer Centre & Royal Melbourne Hospital

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