3.4.1. Donor Selection

The main determinants when selecting a donor whether related or unrelated are as follows:

The “perfect” donor does not exist – no current algorithm will guarantee a positive outcome will always occur.

3.4.2. HLA Match

The most significant factor in success and overall outcome is the degree of match between the donor and recipient.

1.

Most data suggest a 10/10 match is the best choice.

2.

In many circumstance a 9/10 match can be considered as good as a 10/10 but where the mismatch occurs is important. A mismatch at HLA DQB1 has been shown to have the least likely adverse outcome. Worse outcomes have been seen where the mismatch is at class I. Choosing a HLA A, B or C mismatch should be based on local studies and experience as it can be population or ethnically dependent.

3.

Two or more mismatches are associated with a poorer outcome (Shaw 2009).

3.4.3. Cytomegalovirus (CMV) Status

Cytomegalovirus (CMV) is a common virus that can infect almost anyone. Most people don’t know they have CMV because it rarely causes symptoms. However, if you’re pregnant or have a weakened immune system, CMV is cause for concern. Once infected with CMV, your body retains the virus for life.

Where possible the donor-recipient pairing should be CMV matched with preference given to a CMV compatible donor, i.e. negative donor in a CMV-negative recipient. The CMV status of the donor is less important in a CMV-positive recipient, but there is some evidence that a CMV-positive donor is preferable in a CMV-positive recipient as it may protect the patient from CMV infection (Rovira et al. 2012). Analysis has shown that prior donor CMV exposure significantly reduces the risk of CMV reactivation in CMV-positive recipients as immunity against CMV seems to be transferred with the donor cells and protects CMV-positive recipients from reactivation.

3.4.4. Blood Group

Blood group mismatch is not a contraindication to HSCT, and there is conflicting data about the role of blood group mismatch in relation to post HSCT relapse, but the majority of research suggest that is does not influence HSCT outcome (Kulkarni and Treleaven 2009).

Matching donor and recipient blood group may benefit the recipient as it may reduce the number of transfusions and the period of transfusion dependency post HSCT. Blood group matching is an important consideration in transplants where BM stem cells are the product of choice as it removes the requirement for the product to be red cell depleted to reduce the risk of intravascular haemolysis in the recipient.

3.4.5. Sex Match

Donor-recipient sex match is an important predictor of transplant-related mortality (TRM) with the combination of a male recipient with a female donor known to have an increased risk of chronic GVHD and a higher TRM but not necessarily a reduced relapse risk in all diseases.

3.4.6. Parity

If only female donors are available, it is recommended where possible to use a nonparous female donor as -parous females have a higher chance of having HLA-specific antibodies due to exposure to foetal antigens in utero. It is accepted that recipients (either male or female) who have a HSCT from parous donors have a higher risk of chronic GVHD (Kollman et al. 2001).

3.4.7. Age

The younger the donor at the time of HSCT donation has a favourable outcome after HSCT. It appears that the risk of acute GVHD (Grade 3 or above) and chronic GVHD is higher, and overall survival can be lower with increased donor age (Kollman et al. 2001).

3.4.8. Donor Evaluation

All donors should be medically assessed and consented independently from the recipient medical team. The maxim of “Do No Harm” to the donor is paramount, and no donor should be selected where there is a risk of aggravating or exacerbating a potential medical issue in the donor.

Table 3.4 lists the investigations that should be undertaken for all donors. There is a concern that related donors may not always be as forthcoming about their health as they do not wish to jeopardise their relative’s transplant. The table lists the mandatory virology screening that is required on all donors – specific or additional testing may be required in certain countries, e.g. screening for West Nile virus if donor resides in an at risk area, or if the countries’ regulations require it, e.g. Tri-NAT assay.

Table 3.4

Pre-transplant investigations of the donor

3.5.1. Screening of Elderly Donors

With more than 25% of HSCT now being performed in recipients >55 years of age, the chance of a higher age in matched sibling donors is also greater. This group of donors are more likely to have age-related medical conditions, and additional testing may be required to reduce the risk of donor-derived disease, e.g. transmission of an immune-mediated condition, e.g. asthma or psoriasis to the recipient, and reduce the risk to the donor. This includes PSA (prostate-specific antigen) in males, occult blood in stools, possible BM aspirate if results are abnormal, protein electrophoresis and CT chest if there is a history of smoking.

3.5.2. Screening of Paediatric Donors

Paediatric sibling donors are a unique underreported group with special challenges for the HSCT team and the family. Parents of the paediatric donor are in the difficult position of having to consent to both the donation and the transplant. JACIE and other professional bodies suggest the use of independent assessor and donor advocates in the case of paediatric donors to ensure the needs of the paediatric donors are met and that they are protected. Hutt et al. (2015) state that the intense experience of HSCT has a long-term impact on the whole family indicating the need for follow-up and psychological support. There can be a striking difference between the donors’ and parents’ view of the situation with the donor feeling a closer relationship with the recipient and also feeling responsible for them as well as the fact that the recipient owes them a debt of gratitude. Parents are concerned with two children and often feel that the donation process has a positive effect on family life not understanding any negative effect it may have on the donor feeling a pressure to donate or having that feeling of responsibility.

The needs of paediatric donor are sometimes left unmet since parents and healthcare professionals cannot always see the effect of the donation process on them. This can also be said to be the case in adult donors although they at least have life experience and knowledge which enables them to process and deal with their feelings in a way that a child often cannot.

3.5.3. Confidentiality

Information and care of the HSCT patients and their donor should be kept separate. Healthcare professionals must minimise their influence and that of the recipient and other family members which could complicate the potential donors’ decision to donate or not. Families are complex entities, and potential donors and recipients can be estranged or influenced, and donors can feel pressured to donate. A model of care which is independent to the recipient (i.e. independent medical assessment and counselling of the potential donor) increases the potential donors’ sense of security and allows for informed consent or refusal of donation. It is essential to separate the care of the donor from that of the recipient so that each individual can be focussed upon. The privacy of the donor must be respected and protected, and all potential donors should be given information at the time of the HLA typing about the potential process.

3.5.4. Donor Consent and Clearance

All donors should be reviewed and consented prior to the recipient commencing conditioning chemotherapy. They should be medically cleared and understand the implications if they withdraw their consent or participation once the recipient’s conditioning has commenced.

3.5.5. Stem Cell Source

While this is primarily dictated by the transplant medical assessment and the type of HSCT that the recipient is undergoing, the donor will also influence that decision. The donor has a choice in which type of donation method that they prefer, and both should be discussed. The donor may also have medical issues which influence the cell source, e.g. donors with significant back injuries or issues may not be suitable for bone marrow harvest, and unrelated donors who do not have adequate peripheral venous access may not be considered for apheresis due to the reluctance to insert a central access device in an unrelated donor.