Why is stem cell transplantation considered a dangerous procedure for most patients?

When the immune system functions properly, it knows how to distinguish between foreign factors and the body's own tissues. In autoimmune diseases, this recognition mechanism malfunctions: immune cells and antibodies, which are supposed to protect the body from threats, are turned against it and damage healthy tissues. Today, there are drugs that can suppress the activity of the immune system and reduce the damage, but most of the time they do not eliminate the cause of the disease, and therefore prolonged treatment is required.

A study recently published in the journal Med demonstrates the potential of an alternative approach: instead of repeatedly suppressing a faulty immune system, in exceptional cases it may be possible to replace it with a new immune system. Transplants from a donor are already used to treat some cancers, sickle cell anemia, and other blood diseases, but their use in autoimmune diseases is rare. The new study describes two patients who suffered from a severe autoimmune disease of the nervous system and underwent a stem cell transplant from a donor more than 15 years ago. Since then, the disease has not recurred in them, the antibodies that cause it have disappeared from their blood, and they no longer needed treatment against it. The result is interesting, but it involves only two patients and a procedure that involves significant risks.

The antibodies that damage the nervous system

The study followed a man and a woman who suffered from Neuromyelitis Optica (NMOSD) – a rare autoimmune disease that mainly affects the spinal cord and the optic nerve. In most patients with the disease, antibodies are created against the protein aquaporin-4, which is found on the surface of supporting cells in the nervous system. The antibodies trigger an inflammatory response that damages the cells and can cause vision loss, weakness, and even paralysis. The disease is characterized by recurring attacks, and each attack can leave behind additional damage.

In recent years, targeted drugs have been approved that significantly reduce the risk of attacks, but they require continuous treatment, do not necessarily eliminate the antibodies that cause the disease, and not all patients respond to them. The two patients in the study were 28 years old at the time of treatment and suffered from a severe and treatment-resistant disease that continued to flare up despite numerous treatments. They underwent the transplant in 2009 and 2010, even before the targeted drugs for the disease were approved, to which not all patients respond either.

A previous attempt at an autologous stem cell transplant, in which the patient's own stem cells are returned to them after treatment aimed at suppressing the immune system, also failed to stop the progression of the disease. In contrast, in a transplant from a donor, the transplanted stem cells establish themselves in the bone marrow and begin to produce new blood and immune cells, which originate from the donor. Thus, a new immune system is built in the body that originates from another person – but because the cells are foreign to it, the risk also increases that the body will reject the transplant or that the new immune cells will attack the patient's tissues.

For the transplant, each of them received hematopoietic stem cells from a different donor. These are cells that originate in the bone marrow, and from which all blood cells are created, including cells of the immune system. Before the transplant, the patients underwent chemotherapy and immunosuppression, which were intended to destroy a significant part of their existing immune system and make room for the new cells. After that, the donor's stem cells were transplanted into their bodies, which established themselves in the bone marrow and gradually began to produce new blood and immune cells. The new cells were of donor genetic origin, and developed and shaped themselves in the patients' bodies to create a new immune system.

Far-reaching results

The results were extraordinary: after 15 and 16 years of follow-up, both patients did not experience any more attacks and did not need immunosuppressive treatment against the disease. The antibodies against aquaporin-4 disappeared from their blood and did not appear in the new immune system, and imaging tests did not show new lesions in the nervous system. In the man, there was a significant improvement in function – he returned to an independent life and even became a father. In the woman, who suffered from severe neurological damage before the transplant, there was only limited improvement in hand movement, but the disease stopped progressing.

The researchers speculate that the transplant succeeded because it removed long-lived memory cells from the patients' immune system, which continue to produce the harmful antibodies even after other treatments. In addition, they found that in the new immune system there were many regulatory T cells – cells that inhibit the activity of other immune cells and thus prevent them from attacking the body's tissues. However, the study does not prove that the elimination of long-lived memory cells or the changes in the regulatory T cell population were what led to the remission of the disease.

Despite the encouraging result, a transplant of hematopoietic cells from a donor is not a routine treatment for this disease. It can cause serious complications, including life-threatening infections and graft-versus-host disease – a condition in which the donor's immune system cells attack the patient's tissues. Both patients did not suffer from the disease, but one of them needed regular treatment due to a lack of antibodies, and the other was diagnosed with bladder cancer 12 years after the transplant. It is impossible to determine if there is a link between the development of cancer and the transplant, but secondary malignancies are a known risk after treatments of this type.

The study has a major limitation: it involves only two cases, without a control group and without comparison to the modern treatments available today, so it is still not known how many more patients will benefit from this approach, and if the benefits justify the risks. Nevertheless, the long-term follow-up provides interesting evidence that in rare and particularly severe cases, replacing the immune system is not just a way to suppress the disease – perhaps it can stop the mechanism that activates it in the first place.