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Developments Improve Safety of Stem Cell Transplantation in the Treatment of Leukaemia
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Two studies in the field of stem cell transplantation are being presented at the 11th annual Congress of the European Hematology Association (EHA) in Amsterdam, the Netherlands.
The study, conducted at the Leiden University Medical Center (LUMC), demonstrates that environment-specific cells can play a role in positively influencing rejection reactions following stem cell transplants.
The second study, from the San Raffaele Scientific Institute in Milan, Italy, shows that a 'suicide' gene can be used to cut short rejection reactions following stem cell transplants.
Both discoveries make stem cell transplants safer, and signify a step forward in the treatment of malignant blood conditions such as leukaemia.
Firstly, stem cells may be extracted from the bone marrow by multiple aspirations. A transplantation performed with these stem cells is known as a bone marrow transplant.
Stem cells can also be harvested from the blood, in which case it is known as a stem cell transplant.
The patient is given healthy, functional stem cells intravenously, i.e. directly into the bloodstream.
These stem cells find their way to the bone marrow in the bones, and start producing blood cells. This is important for the patient's recovery.
A common complication that occurs after stem cell transplantation is a rejection reaction in the patient's body, which can potentially be fatal.
Stem cells are located in an environment that is unique to bone marrow. Currently, only the blood-forming stem cells are used in a stem cell transplant, and not the cells located around them.
The LUMC study showed that these environment-specific cells play an important role in mediating potential rejection reactions subsequent to transplantation.
Rejection of the stem cell transplant by the patient's body is one of the problems associated with stem cell transplants in the treatment of leukaemia and other diseases.
These environment-specific cells, known as mesenchymal stem cells, can suppress immune reactions in the body.
Professor W.E.Fibbe of the LUMC, said, "One of the exciting things about this discovery is that these environment-specific cells can not only suppress immune reactions, but also activate them, depending on the donor or receiver."
"This property of environment-specific cells has not been identified in this way before."
He continued, "The study was originally conducted by the LUMC with the goal of suppressing undesirable rejection reactions following stem cell transplants, but this discovery will allow us to investigate a large number of new possibilities."
In the future, this insight may be applied to organ transplants and the treatment of other diseases, including auto-immune diseases.
The second study, conducted by the San Raffaele Scientific Institute in Milan, achieved three goals:
- Availability of a donor for virtually every patient with leukaemia;
- Mediate the rejection reaction more effectively with the aid of 'suicide' gene therapy;
- Achieve faster immune system recovery in order to fight life-threatening infections.
Generally, siblings are tested to find an exact tissue match. The odds of success in this scenario are low (25%). In this Italian study, family donors were used who were only a 50% match for the receiver. This allowed a suitable donor to be found for every patient.
The immune cells present in the stem cell transplant can cause serious rejection reactions in the receiver; this is called the graft-versus-host reaction.
This is accompanied by life-threatening symptoms which occur mainly in the skin, liver and intestines. At the same time, the donor's immune cells also attack the leukaemia cells in the receiver: the graft-versus-leukaemia reaction.
These immune reactions following stem cell transplantation were effectively combated by Dr. F. Ciceri's group with the help of so-called 'suicide' gene therapy.
A gene is introduced into the donor immune cells, and when triggered by a specifically tailored drug, the immune cells 'commit suicide', bringing the damaging immune reaction to a halt.
Dr. Ciceri has successfully used infusions of genetically modified donor immune cells after transplantation, allowing the patient-receiver's immune system to restore itself more quickly, lowering patient mortality due to serious infections from the historic 53% to 12.5%.
