Sickle cell disease or sickle cell anaemia is a chronic, hereditary blood disease that is notoriously hard to treat. Patients often suffer lifelong severe pain attacks and other health problems. Up until recently there was no effective treatment for adult patients, but the advent of stem cell transplantation has changed that. The treatment was already offered in the USA, but since recently Amsterdam UMC offers stem cell transplants in the Netherlands. Dutch scientists have improved the American regime so that patients are not only cured, but also do not have to take medication anymore. Ten adult patients have been cured so far.
Red blood cells are produced by stem cells within the bone marrow. A genetic defect causes red blood cells to take on a crescent or sickle shape in patients. These sickle shaped blood cells are broken down much quicker than healthy blood cells. Their shape also impairs their movement through blood vessels. Sickle cells tend to get entangled and can get stuck in a blood vessel. This leads to a deficiency in oxygen supply to organs and tissues, that can suffer damage as a result of this. This process can cause periods of severe pain. On top of this, sickle cell patients suffer from chronic anaemia and are more vulnerable to all types of infection. Their life expectancy is much shorter than average, at around 54 years.
Stem cell therapy involves changing mutated stem cells for healthy stem cells from a donor, usually a sibling. This treatment has been used on children with sickle cell disease, but not in adults. The reason is that in order for this stem cell transplant to be successful, the recipient’s immune system needs to be shut down, so that the new cells aren’t attacked and destroyed by the patient’s white blood cells. Heavy doses of chemotherapy ensure that the immune system of the recipient is neutralized, and that the mutated stem cells are destroyed. This treatment is too severe for adult patients, because their organs have already been damaged by the sickle cell disease over a longer period of time. Children still have healthy organs, which makes the chemotherapy treatment less dangerous.
The novel American treatment uses low dose radiation instead of chemotherapy, as well as administering antibodies. In this manner, the recipient’s body is prepped to receive donor stem cells.
In 85% of cases, this treatment succeeds and cures the patient of sickle cell disease, but 15% of patients experience rejection of the donor cells. Additionally, cured patients have to continue taking heavy doses of immunosuppressants. This means that their immune system is permanently compromised. These people will have to apply extreme caution in avoiding infections, which often involves profound lifestyle changes. Furthermore, these drugs come with all sorts of side effects, such as joint pains, acne and raised cholesterol levels.
Scientists in Amsterdam have found a way to circumvent these after-effects by adding a pre-conditioning phase to the existing American stem cell transplant protocol. Prior to the transplant, the patient is treated with drugs that reduce activity in the bone marrow. Typically, the bone marrow of sickle cell patients is very active in producing new blood cells. Basically this means that there simply isn’t room to fit in the new donor stem cells. Apart from that, sickle cell patients have a highly active immune system. The Amsterdam scientists hoped that reducing activity in the bone marrow would results in better acceptance of the donor stem cell.
This turned out to be the case. Over the past 2 years, 10 patients have been treated in Amsterdam with the pre-conditioning phase preceding the actual transplant. Thus far, all transplants have been a success without any rejection reactions. Even more promising is that all 10 patients have been able to completely reduce their immunosuppressant intake after the transplant to zero. The ten ex-patients are still being monitored by the Amsterdam UMC scientists in order to assess whether damaged organs and tissues recover over time. Also the effects on social and psychological wellbeing are being evaluated.