Stem cell transplant risks mitigated with stem cell therapies

While stem cell transplants can save the lives of people living with different life-threatening conditions, they also entail risks for both donors and recipients, but new stem cell therapies might offer solutions.

Stem cell transplants treat conditions – such as leukaemia, myeloma and lymphoma – in which the bone marrow is damaged and can no longer produce healthy blood cells. The replacement cells can either come from a patient’s body or a donor.

Every year, around 40,000 stem cell transplants take place in Europe, which continues to grow thanks to medical advances despite the slowdown during the COVID-19 pandemic in 2020. 

More transplants mean that more patients receive the treatment they need. However, it also implies a greater need for post-transplant care and addressing diseases associated with the procedure. 

One of the most tricky aspects of stem cell transplants is the need to find a suitable donor. For a person to be able to receive a transplant, there needs to be a match of human leukocyte antigens (HLA), which are proteins in most cells in your body that the immune system uses to see which cells belong in your body and which do not. 

Tissue types are inherited, meaning the best chance to find a match is with a sibling from the same two biological parents. However, 70% of patients do not have a full match in their family, relying on external donors. 

When this is the case, the probability of finding a match is not the same for everyone. There’s often a shortage of donors from diverse ethnic backgrounds, as patients from minority groups might have difficulty finding a suitable donor due to the genetic complexity of matching stem cells.

Another complex facet of donations is the possible complications after the procedure.

The most common side effect of a stem cell transplant is graft-versus-host disease (GVHD), a complication that occurs when the donor stem cells, the graft, attack healthy cells in the patient, the host.

Acute GVHD usually develops within the first 100 days after transplantation, and it affects approximately 30 to 60% of patients who undergo an allogeneic stem cell transplant.

Most of the risk factors that can contribute to GVHD are related to the donor – the older age of the donor, sex and whether there is an HLA mismatch.

And while recipients of a donation are exposed to risks, so are those who donate their stem cells.

Taking this into account and broadening the scope of donations, the European Parliament put forward an update on regulating substances of human origin (SoHO). The text states that SoHOs should be obtained from individuals whose health status can guarantee that no adverse effects occur due to the donation.

The Parliament also adds that the regulation should include principles and technical rules to monitor and protect donors, which they consider “particularly important where the donation involves significant risk to the donor’s health”. 

Stem cell transplants fall under this definition as there is a need for pre-treatment with medicinal products and a medical intervention to collect the substance. 

“As different types of donation entail different risks for donors, with varying levels of significance, the monitoring of donor health should be proportionate to those levels of risk”, states the Parliament’s text. 

The potential of new therapies

Anna Couturier, senior project manager at The European Consortium for Communicating Gene and Cell Therapy Information (EuroGCT), told Euractiv that the future of stem cell therapies moves away from traditional transplants to new advanced therapies (ATMPs) that will minimise the risks of donations and facilitate treatment. 

“It cuts out the difficulties, this whole infrastructure that we have for donations, because you don’t have things like GVHD, you don’t have rejection from the body”, Couturier said. 

These new therapies mean that the procedure won’t longer need an external donor as they will allow editing patient’s cells or genes without introducing any foreign actor. 

According to the European Medicine Agency (EMA), stem cells are categorised as ATMPs when these cells undergo substantial manipulation or are used for a different essential function.

“We’re standing on an absolute precipice of approvals coming from the European Medicines Agency of new gene and cell therapies. In the next five years, it’s going to be unbelievable the differences in what treatments are available”, she said. 

One of the examples of the potential of these therapies is Casgevy, a cell-based gene therapy medicinal product, which the EMA recommended for approval on 15 December. 

This therapy is the first one that uses CRISPR/Cas9 technology, which allows editing of a patient’s blood stem cells. 

Casgevy is indicated to treat transfusion‑dependent beta-thalassemia and severe sickle cell disease, two inherited rare diseases caused by genetic mutations that affect the production or function of haemoglobin – the protein found in red blood cells that carries oxygen around the body. Both diseases are life-long, debilitating and life-threatening.

The EMA states that Casgevy is indicated for “patients 12 years of age and older for whom haematopoietic stem cell transplantation is appropriate and a suitable donor is not available”.

Despite the big advances these therapies bring, Couturier added that “whether we are all up the task of making sure these new treatments reach patients safely, fairly, and accessibly is another question”. 

She also warned about the need to stay cautious and the long way ahead in the next years to unleash these new treatments’ full potential.

[Edited by Alice Taylor]

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