Graft-versus-Host Disease: Know your donor

For more than five decades, Haematopoietic (blood-forming) stem cell transplantation has been recognised as potentially curative therapy for certain types of cancer and non-malignant disorders.

Umbilical cord blood has emerged as a viable alternative source of blood-forming stem cells which could be made available, without delay, to the child or a sibling. Parents now have the ability to store (‘cryopreserve’) their newborn baby’s cord blood stem cells in a family cord blood bank.

Once done, a cord blood transplant (CBT) becomes an option for the Transplant Team and may obviate the need to search for a matched, unrelated donor.

One of the main benefits of cord blood, as a source of stem cells, include the simplicity of collection at the birth of the baby, with no risk to mother or baby. There are two ways of collecting the stem cells:

  • The ability to immediately bank these samples in a family (private) stem cell bank, for future use by the child (donor) or a sibling.
  • Cord blood stored in ‘public’ cord blood banks are made available for use by non-related individuals. These cord blood stem cells can be made available for transplant, without delay, and are more ‘naïve’ than the other sources of blood-forming stem cells i.e., bone marrow (BM) and peripheral blood stem cells (PBSCs).

Defining Graft-versus-Host Disease

The day-to-day task of a person’s immune system is to protect it from foreign invaders, be it a bacteria, virus or other organisms or cells that are not identified as ‘self’.

When a person needs a stem cell transplant, a donor, who is a match for the specific patient, must be found. This is what we call Human Leukocyte Antigen (HLA) matching or, in non-medical terms, “flags” that the immune system must look at to determine if something is an invader. With a stem cell transplant, the recipient will receive donor stem cells and these cells will form new blood as well as an immune system in the recipient.

Higher levels of differences of human leukocyte antigen (HLA) matching can be tolerated with CBT, confers a potential advantage. Also, some studies have shown a lower incidence of graft-versus-host disease (GvHD) with CBTs compared to bone marrow and peripheral blood stem cell transplants.

These features make a cord blood transplant as a potentially important option in patients from diverse, cultural and ethnic backgrounds as, for these patients, it can often be challenging to locate a matched unrelated donor (MUD).

With a stem cell transplant, even after HLA matching, the patient/recipient’s body will still see small differences between the new developing immune system and other cells in their body. Therefore, the recipient’s “new” immune system may harm some of the recipient’s cells because they are seen as “different”. This immune attack (on the recipient) is called Graft versus Host Disease (GvHD). The word ‘graft’ referring to the donor’s cells, and the ‘host’, to the patient (recipient).

The good of GvHD

GvHD can have a ‘good’ aspect as it indicates that the recipient’s new immune system is working and is likely to be attacking any remaining or returning disease. This type of immune response is called ‘graft versus leukaemia effect’ or ‘graft versus tumour effect’. However, extreme GvHD can cause undesirable problems and side effects which is life threatening.

The not-so good

GvHD is complex and cannot be predicted. Approximately, 30-40% % of transplant recipients will show signs of GvHD. In certain cases, it is mild but, in severe cases, may be life-threatening.

GvHD can be classified as the following:

  • Acute: occurring within the first 100 days after transplant
  • Chronic: usually occurring after 100 days and
  • Overlap: having features of both acute and chronic GvHD.

GvHD affects organs such as the skin, liver, and gastrointestinal system.

It usually requires a fine balance of medication to keep the disease under control. Treatment includes localised and/or systemic steroids or immunosuppressive medication. In some cases, acute or chronic GvHD cannot be controlled with these medications and further treatment, such as extracorporeal photopheresis (ECP) (where the white blood cells that cause GvHD are destroyed with medication and ultra-violet (UV) light, is required).

Several strategies exist to further improve outcomes in CBT and minimise GvHD even further:

  1. The use of double CBT from unrelated donors
  2. The use of HLA-identical sibling CBT
  3. The use of a combination of UCB and bone marrow from the same sibling,
  4. The use of higher cell doses in conjunction with microenvironmental factors and, for example, the combined use of mesenchymal stem cells.

These strategies are designed to enhance the ‘homing’ and engraftment of the transplanted cells and improve success rates overall.

Final words

Parents should consider storing their baby’s stem cells at birth, which would give the Transplant Team an option should a stem cell transplant be needed.

Did you know

Since the first cord blood transplant in 1988, more than 40,000 CBTs have been performed, worldwide, over the past three decades.