We learn about the specialised and complicated allogeneic stem cell transplants.
Allogeneic transplants – obtained from a donor
Allogeneic transplants, also known as an allograft or donor peripheral blood stem cell transplant (PBSCT), differ from autologous transplants in that the stem cells are not obtained from the patient’s body but from a donor who may be related, or a matched unrelated donor (MUD). This type of transplant is much more specialised than an autologous transplant and a lot more complicated.
What diseases do allogeneic transplants treat?
- Acute myeloblastic leukaemia; acute myelogenous leukaemia (AML)
- Chronic myelogenous leukaemia (CML) – this disease has more treatment options now other than a transplant due to a monoclonal antibody.
- Chronic lymphocytic leukaemia (CLL)
- Hodgkin’s lymphoma (NL) and non-Hodgkin’s lymphoma (NHL)
- Aplastic anaemia
- Multiple myeloma
- Myelodysplasia syndrome (MDS)
Though, research is being carried out on other conditions, to expand treatment.
How does an allogeneic transplant work?
Peripheral blood stem cells (PBSCT) are taken out of circulating blood from the donor and used to replace diseased marrow in the patient.
Once harvested, the stem cells will be tested. They can be transplanted to the donor on that day, or can be frozen while the patient is undergoing conditioning.
Once the patient is ready for the transplant, the stem cells are defrosted. The unit I worked for generally used cryopreservation (use of very low temperatures to preserve structurally intact living cells and tissues). However, in the case of cells arriving from another country, one unit was infused directly into the patient and the other half of the collection was sent for cryopreservation for later use, if needed.
Donors are found from donor registries either locally (The South African Bone Marrow Registry (SABMR)) or internationally.
The registries rely on people joining and having a small amount of blood taken, to be tested for an early human leukocyte antigen (HLA)/tissue typing level. HLA is present in the white blood cells/tissues in the body and the antigens tell us the tissue typing. These results are then registered on the database.
A donor may be a match for someone in South Africa or overseas as all registries co-operate. A match may happen quickly or a donor may be on the database and not get called for years. It all depends on their typing.
The Sunflower Fund, a SA non-profit organisation, works to promote stem cell drives and sponsors some of the cost of typing. Through their great work, South Africaís database is growing.
Identifying a donor
Finding a matched donor is the key to a successful allograft. Donors may include:
- HLA-matched relative – usually a brother/sister.
- HLA-matched unrelated donor (MUD).
- HLA-mismatched family donor (only if the degree of mismatching is not overwhelming and no possible registry donor is available).
- Unrelated umbilical cord blood stem cells. Note, these are not available in South Africa as there is no registry yet for donor cord blood cells. Some overseas registries have a database and they’re available to South Africa.
Siblings are tested first and a sibling donor is the jackpot. If there is no match in the family then the patient’s tissue typing is compared to records of donor typing, until hopefully a match is found in South Africa or internationally. This can take up to four months and longer. The waiting time is tense and either a donor is found, or disappointingly not.
A transplant from a MUD donor, even if a complete match at all levels of testing, carries more risks than from a matched sibling. Though, the typing worldwide is getting better as well as the knowledge of how to care for a transplant recipient following transplantation.
A mismatch donor can lead to a much more complicated transplant and less success, and is only ever considered in a serious case.
An allograft is extremely expensive, especially if it involves an overseas donor so it’s essential that the patient’s medical aid covers it. Though, sadly some medical aids don’t. Certain medical aids will only cover a local donor.
I have had families raising money themselves to facilitate getting a donor, which only makes the whole process that more stressful.
Unfortunately, not all oncology centres have transplant units so there is a chance that a patient will be far away from home while undergoing an allograft.
What makes a good candidate (patient)?
The patient’s disease needs to be in good remission; the patient must be under the age of 60, and in general good health and fitness with no chronic illness, such as diabetes, hypertension, heart-, kidney- and liver disease. They must also not have any active viral disease, such as cytomegalovirus (CMV). Then, obviously, there must be a fully matched donor. The oncologist will assess all these factors before giving the go ahead.
The transplant process
The patient needs to undergo conditioning. A treatment regime will be given; this regime needs to obliterate any diseased marrow and make space for the new donor cells to grow into. The regime can include chemotherapy and sometimes total body irradiation (TBI) (radiotherapy to the whole body), but this depends on the type of disease and the treating oncologist.
The patient will receive either oral or IVI busulfan, which is a chemotherapy agent, to ‘empty’ the bone marrow. It may be combined with another chemo agent, such as IVI fludarabine, to suppress the immune system. Once again, the oncologist will decide this.
In the centre where I worked, we performed ‘mini-transplants’ – less toxic conditioning regimen but again this all depends on the disease and status of.
Most of our patients underwent their conditioning as outpatients, depending on the oncologist and regimen.
Once the conditioning is completed and a rest day/days taken, the transplant takes place. The stem cells from the donor are infused into the recipient.
After the infusion, the bloods are scrutinised for signs of engraftment (donated stem cells have settled and are starting to produce all the normal blood cells required). This usually becomes noticeable around the 10th day but can be earlier or later.
The recipient is in isolation with barrier nursing for up to four weeks. An immune suppressant is started the day prior to transplant to dampen an immune response against donor cells. It can continue for a year following transplant or longer.
Patient/oncologist/Transplant Sister follow-up with recipient cannot be stressed enough following the transplant. Communication and support is essential to stop any problems promptly.
At the same time as the donor cells are starting to work, oncologists and nurses are looking out for graft versus host disease (GvHD). This disease is specifically related to transplants.
What is GvHD?
GvHD occurs due to the immune system present on the donor cells recognising they’re in a foreign environment and attacking the host cells.
It can be very serious and life-threatening, and if not controlled can attack most commonly the skin, liver and digestive system causing severe complications.
Saying this, we do need some GvHD to give a ‘graft versus tumour effect’. In other words, an immune response to recognise any malignant cells if they reappear in the recipient. Complicated, isn’t it?
The oncologist will be very aware at this stage and treatment is given carefully to prevent a surge of GvHD. This condition can occur at any time following a transplant and can later become chronic. Despite a 100% match, GvHD can still occur.
This means the donated cells do not engraft. It can also be a life-threatening complication due to loss of an immune system and risk of severe infection, due to no new marrow cells to take over normal cell production.
This is a serious liver problem, caused by the chemo/radiation prior to transplant and can be life-threatening.
Other possible long-term complications include infertility, cataracts, depression, lung and heart problems, relapse of original disease.
MEET OUR EXPERT – Mary Farrell
Mary Farrell (SRN SCM) is a retired stem cell co-ordinator. She trained at General Infirmary Leeds 1970-74, and is also a previous Hospice Sister/Chemotherapy Out-Patient Sister.