Choosing a haematopoietic stem cell match

 Looking for a haematopoietic stem cell match? There’s more to it then swiping right. Dr Lucille Sarah Singh explains why.

You can listen to this article below, or by using your favourite podcast player at pod.link/oncologybuddies

What is a haematopoietic stem cell transplant?

A haematopoietic stem cell transplant (HPSCT) offers the potential for cure in certain malignant, inherited and auto-immune diseases as well as bone marrow failure conditions. It involves infusing healthy haematopoietic stem cells into patients. An autologous HPSCT is when a patient’s own stem cells are used. An allogeneic HPSCT is when donor stem cells are infused, and this is where the search for that perfect haematopoietic stem cell match comes in. 

First successful bone marrow transplants

The first successful bone marrow transplant was performed in 1956 by Dr E D Thomas who treated a child with leukaemia, using donor bone marrow from the child’s identical twin. An identical twin donor means that there is no risk of rejecting the donor stem cells and no risk of the donor cells attacking the patient’s cells. The availability of a twin donor whilst ideal is a rarity in practice. In 1973 the first successful bone marrow transplant using an unrelated donor occurred. Building on these successes and with improvements in post-transplant care and anti-rejection therapies, transplants can now also be performed in partially-matched cases (haplo-identical transplants), meaning parents and children can now become each other’s donors where fully-matched donors are unavailable. 

What exactly are we matching up? 

Human leukocyte antigens (HLA). These are proteins found on the surfaces of your cells. HLA-A, HLA-B, and HLA-C are found on all your cells. HLA-DP, HLA-DQ and HLA-DR are found specifically on the surfaces of specialised immune cells. Genes on chromosome 6 encode all of these proteins and are highly polymorphic, essentially meaning there are many versions of normal when it comes to HLA proteins. 

The best-case scenario would be for the patient and donor to have the same versions across all the HLA classes. Fully-matched related donors are preferred over fully-matched unrelated donors. 

Haplo-identical related donors (mismatches present) are used when no fully-matched donors (related or unrelated) are available. ABO blood grouping is also done and whilst ABO matching is preferred, ABO incompatibility is not a barrier to transplant as therapeutic interventions can be undertaken pre- and post-transplant to mitigate the complications this may cause. 

Tick box list

Other considerations, outside of the above, also play a role in terms of increasing the likelihood of a successful transplant. Younger donors are preferred (<40 years). Male donors are preferred over female donors as there is a higher risk of graft-vs-host disease with female donors. 

Patients and donors are also screened to see if they have been exposed to viral infections. Cytomegalovirus is a virus that can cause serious and debilitating infection in the post-transplant period. Patients and donors are screened for previous exposure to this virus and the combination of a negative donor and negative patient or a positive donor and positive patient is preferred. Even once a potential donor has ticked all the boxes for an acceptable match, they are subjected to a thorough medical review to determine if they are healthy enough to be a stem cell donor. It does sometimes happen that further testing reveals medical problems they were unaware of which excludes them from donating stem cells. 

Medical aid obstacles

The transplant has to be approved and funded by the patient’s medical scheme. Annexure A of The Medical Schemes Act, 131 of 1998 states that bone marrow transplants should only be covered if the patient is under 60. Furthermore, it goes on to say that allogeneic transplants will only be considered if there is an HLA-matched family donor (no unrelated donors even if fully-matched) and only in first remission. 

This latter part is particularly problematic in that even if a second remission is attained, because the transplant wasn’t requested in first remission (bearing in mind that there is no medical indication to transplant most cancers in first remission), the transplant will be declined by the certain medical schemes who strictly adhere to this legislation despite the medical indication for transplant being sound. 

This legislation unfortunately is a barrier to performing HPSCTs in a significant proportion of patients where it’s medically indicated. This marginalised group of patients succumb to their disease 100% of the time. 

Image by stock.adobe.com