A promising therapy ends a decade of daily blood transfusions to survive

BarcelonaIt has been a year since she last received blood transfusions, but until very recently she needed one a day to survive. In the last decade, she tried up to nine different treatments, using all sorts of strategies such as antibodies, steroids, or immunosuppressive drugs. But none of them had a lasting impact. This is the case of a 47-year-old woman with three complex and serious diseases that caused her immune system —that is, the body's defenses— to mistakenly attack her own cells as if they were an external threat.

As she had exhausted conventional therapeutic alternatives, professionals at the Hospital of Erlangen, in Germany, proposed a treatment with CAR-T cell immunotherapy, a therapy in which the patient is their own donor. Specifically, the patient's T lymphocytes (which are natural defenses) are extracted, genetically reprogrammed in the laboratory so they do not attack healthy cells, and re-inoculated into the bloodstream. Since receiving this treatment —which revolutionized the treatment of some cancers such as blood cancers a few years ago—, the patient no longer needs transfusions or other treatments for now.

"The treatment was extremely effective in eliminating the three autoimmune diseases at once," assures Fabian Müller, the author of the study published this Thursday in the journal Med by Cell Press, which describes this milestone. The expert, who works at the Hospital of Erlangen, highlights that after more than a decade of being ill, the patient is now in remission, meaning there are no symptoms of any of the three diseases, and she can return to an almost normal life. "This therapy has significantly improved her quality of life," he states.

The patient's immune system mistakenly attacked and destroyed her red blood cells due to a disease called severe autoimmune hemolytic anemia (AIHA). Furthermore, her defenses also destroyed platelets due to a second condition, immune thrombocytopenia (ITP), and she had a higher risk of dangerous blood clots due to antiphospholipid antibody syndrome, the third and final autoimmune disease she suffered from. Consequently, she had to receive a blood transfusion every day, as well as permanent anticoagulant medication. Last year, the patient met with Dr. Müller's team, who had already successfully used CAR-T to treat severe autoimmune diseases, such as lupus, a disorder that causes the body's defenses to go out of control and attack healthy tissues. .

Redesigning defenses outside the body

To develop the therapy, the team extracted the patient's white blood cells and isolated her T lymphocytes, the immune cells that actively scan the body for infected or abnormal cells and destroy them. The researchers then re-engineered the patient's T lymphocytes to recognize a protein called CD19, which is present on immune cells that produce antibodies, called B lymphocytes. They then infused the CAR-T lymphocytes back into the patient and eliminated all of her B lymphocytes, as the authors believed they were responsible for the three diseases.  

The clinical effects were almost immediate. The patient needed her last blood transfusion just one week after treatment. Two weeks later, she reported feeling stronger and able to carry out daily activities. Three weeks after completing treatment, her hemoglobin levels, a protein in red blood cells, doubled and returned to normal, suggesting her immune system was no longer destroying her red blood cells.  

"After more than ten years of illness, the patient's blood counts normalized within weeks. The speed and depth of the response were remarkable," celebrates Müller. Although this is a single case, and therefore much more evidence is needed to draw conclusions about the potential of this type of therapy, the authors believe that using CAR-T therapy earlier for patients with severe autoimmune diseases "could help prevent complications from years of ineffective treatments, avoid organ damage, and return patients to their lives," concludes the expert.