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Transplantation

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Keypoints

  • Transplants are used after high-dose chemotherapy to help replace the immune system and bone marrow
  • Patients with aggressive relapsed non-Hodgkin's lymphoma are offered transplants, along with those who do not respond to chemotherapy
  • The transplant can be from another person or, more often, from the patient themselves, with the cells needed for the transplant collected before the high-dose chemotherapy

Introduction

Stem cell transplantation (or bone marrow transplantation) is offered to some patients with non-Hodgkin's lymphoma. Stem cells are the immature blood cells that form in bone marrow. They develop into the mature blood cells - red blood cells, white blood cells and platelets.

Transplantation involves the use of very high-dose chemotherapy (sometimes with radiotherapy) that destroys the bone marrow. The destroyed bone marrow must then be restored with the transplanted stem cells.

A stem cell transplant can be either be:

  • Allogeneic, in which the stem cells come from another person - a donor. The donor may be a relative, ideally a twin. Otherwise, they could be a brother and sister. Another unrelated, but matched, person may also donate marrow
  • Autologous, in which the patient's own stem cells, collected before the high-dose chemotherapy, are transplanted back into them
Transplantation involves the use of high-dose chemotherapy that destroys bone marrow, which is then replenished with the transplanted cells. Click on the picture to go to an animation explaining transplantation

Stem cell, bone marrow transplantation

Stem cell transplants in non-Hodgkin's lymphoma are usually autologous, although allogeneic transplants are becoming more common.

There are two main types of transplantation, depending on the source of the stem cells:

After the high-dose chemotherapy has destroyed the marrow and before the marrow has recovered, the main risk is infection. This risk period lasts for a few weeks, during which time the patient stays in hospital. Antibiotics and top-up blood transfusions may be given.

Transplantation may be used in patients whose non-Hodgkin's lymphoma has relapsed as an aggressive form of the disease, whether or not it was indolent or aggressive at the time of diagnosis.

It can also be used in patients with aggressive non-Hodgkin's lymphoma that does not respond to ordinary chemotherapy, and in those with indolent non-Hodgkin's lymphoma in order to increase the chances of remission. It is also used in some of the rarer forms of non-Hodgkin's lymphoma that are known to be resistant to chemotherapy.

Peripheral blood cell transplantation

In peripheral blood cell transplantation, which is the most common form of stem cell transplant, the source of stem cells is the circulating blood, rather than the bone marrow. Patients with non-Hodgkin's lymphoma can either have an autologous or an allogeneic peripheral blood cell transplant, depending on whether or not their own stem cells are suitable for use, and whether a suitable donor can be found.

In both cases, the stem cells which are going to be transplanted, whether from the patient themselves or a donor, are first encouraged to be produced in greater quantities in the bone marrow and spill over into the blood. This is achieved by the injection of proteins called growth factors, such as G-CSF, which is also made naturally by the body. The growth factor is given daily as a small injection under the skin over between 4 and 5 days.

To collect the stem cells for the transplant, a machine called a cell separator removes blood from a vein in the arm, taking out the stem cells and then returning the blood to the patient. This may involve visiting the hospital for several hours over a few days. It is not a painful procedure and no general anaesthetic is needed. The cells are stored until needed.

In order to rid the body of any remaining cancer cells, the patient then undergoes high-dose chemotherapy, sometimes with radiotherapy, which destroys the bone marrow (myeloablation) and reduces the body's immune system (immunosuppression). Treatment takes several days, and is given in hospital.

A stem cell transplant is then performed, in which the stem cells, whether taken from the patient themselves or a donor, are injected into the patient, almost always through a central line.

The patient then remains in hospital for a few weeks while the bone marrow recovers. As the risk of infection is high during this period, special precautions, including giving antibiotics and special nursing procedures, will be taken. Blood transfusions may be given from time to time.

When the bone marrow and the number of cells in the blood have returned to normal, the patient is discharged from hospital and followed-up as an outpatient.

This technique has promising results, especially in patients with indolent non-Hodgkin's lymphoma. Unlike bone marrow, stem cells can be removed without using a general anaesthetic.

There are important differences between an autologous and an allogeneic peripheral blood cell transplant.

Autologous transplantation

Patients whose own stem cells are suitable for peripheral blood cell transplant are often given doses of chemotherapy drugs before the G-CSF. This both reduces the chances of any lymphoma cells being in the bone marrow and temporarily suppresses stem cell production.

When the bone marrow is recovering from the chemotherapy, the number of stem cells produced by the bone marrow rapidly increases, encouraged by the G-CSF.

After the stem cells have been harvested from the patient, they are cryogenically frozen. The patient then receives high-dose chemotherapy followed by the re-infusion of the previously harvested stem cells.

As the cells come from the patient themselves, the chances of an immune reaction between the patient's immune system and the transplanted cells is drastically reduced. Nevertheless, the risk of infection while the bone marrow is recovering is high, and it is important that patients talk to the lymphoma team about reducing the chances of infection.

Allogeneic transplantation

As a sibling or matched unrelated donor will not have non-Hodgkins's lymphoma, they will not need to have chemotheraphy before their stem cells are harvested. The harvest can also be performed exactly when the patient is ready, so the stem cels are infused fresh after being transported from the donor to the patient, which can either be within the same hospital or from one hospital to another.

Although the success rate with allogeneic peripheral blood cell transplantation is potentially higher than with an autologous transplant, as the donor will not have any trace of non-Hodgkin's lymphoma, there are more risks to patients who have this form of treatment.

As the transplanted cells, no matter how closely matched the donor has been, are not identical to those from the patient themselves, an immune reaction could occur. The patient's immune system could 'reject' the donated cells and attack them as if they were infecting bacteria. More importantly, the patient could suffer 'graft-versus-host-disease', in which the transplanted immune cells attack the patient's own cells as being 'foreign' to the donor immune system. Untreated, this can cause diarrhoea, skin rashes and liver damage, and may become very severe or even life threatening.

However, there are drugs that can be given to limit the effects of graft-versus-host-disease, and doctors may 'purge' donated stem cells of a type of T cell that is thought to cause the reaction, especially if the donor is unrelated and not able to be closely matched.

Bone marrow transplantation can sometimes be autologous (using the patient's own cells), but is usually allogeneic (using cells from a matched donor)
Autologous or allogeneic bone marrow transplantation

Bone marrow transplantation

Bone marrow transplantation is a variation of peripheral blood stem cell transplantation. In peripheral blood cell transplants, stem cells are mobilised from the bone marrow to the blood where they can be harvested easily. In bone marrow transplants, the stem cells are harvested from the bone marrow itself, which requires a general anaesthesia for the patient or donor.

Patients with non-Hodgkin's lymphoma can either have an autologous or an allogeneic bone marrow transplant, depending largely on the disease situation, facilities and experience of the centre and whether or not their own bone marrow is suitable for use, and whether a suitable donor can be found. Peripheral blood stem cell transplant has largely replaced bone marrow transplant today.

In both autologous and allogeneic bone marrow transplantation, about a week or two before the bone marrow is taken, the patient themselves or the closely matched donor may have 1-2 pints of blood taken. This will be given back to them when the bone marrow is collected.

During the actual procedure, the cells are harvested from the bone marrow of the pelvic bone, under general anaesthetic, and the bone marrow is stored until needed. This is usually followed by an overnight hospital stay. As the procedure is demanding, whether it is the patient themselves or a matched donor who is the source of the stem cells, it is generally only performed in patients under 65 years of age who are in good health.

In order to rid the body of any remaining cancer cells, the patient then undergoes high-dose chemotherapy, sometimes with radiotherapy, which destroys the bone marrow (myeloablation) and reduces the body's immune system (immunosuppression). Treatment takes several days, and is given in hospital.

A bone marrow transplant is then performed, in which the bone marrow, whether taken from the patient themselves or a donor, is injected into the patient, almost always through a central line.

The patient remains in hospital for a few weeks while the bone marrow recovers. As the risk of infection is high during this period, special precautions, including giving antibiotics and special nursing procedures, will be taken. Blood transfusions may be given from time to time.

When the bone marrow and the number of cells in the blood have returned to normal, the patient is discharged from hospital and followed-up as an outpatient.

There are important differences between an autologous and an allogeneic bone marrow transplant, and it is important to discuss these between the lymphoma team before starting on treatment.

Autologous transplantation

Although it is more usual for patients whose own cells are suitable for bone marrow transplant to have a peripheral blood cell transplant, the lymphoma team will some times recommend an autologous bone marrow transplant.

After the bone marrow has been taken from the patient, it is cryogenically frozen until the patient's remaining bone marrow has been destroyed and they are ready to receive the transplant.

As the bone marrow comes from the patient themselves, the chances of an immune reaction between the patient's immune system and the transplanted cells is drastically reduced. Nevertheless, the risk of infection while the bone marrow is recovering is high, and it is important that patients talk to the lymphoma team about reducing the chances of infection.

Allogeneic transplantation

As the source of the bone marrow is a sibling or matched unrelated donor, the harvest must be performed exactly when the patient is ready, so the stem cells are infused fresh after being transported from the donor to the patient, which can either be within the same hospital or from one hospital to another.

Although the success rate with allogeneic bone marrow transplantation is potentially higher than with an autologous transplant, as the donor will not have any trace of non-Hodgkin's lymphoma, there are more risks to patients who have this form of treatment.

As the transplanted cells, no matter how closely matched the donor has been, are not identical to those from the patient themselves, an immune reaction could occur. The patient's immune system could 'reject' the donated cells and attack them as if they were infecting bacteria. More importantly, the patient could suffer 'graft-versus-host-disease', in which the transplanted immune cells attack the patient's own cells as being 'foreign' to the donor immune system. Untreated, this can cause diarrhoea, skin rashes and liver damage, and may become very severe or even life threatening.

However, there are drugs that can be given to limit the effects of graft-versus-host-disease, and doctors may 'purge' donated stem cells of a type of T cell that is thought to cause the reaction, especially if the donor is unrelated and not able to be closely matched.


 

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