This clinical trial has the potential to prevent thousands of miscarriages and infant deaths from alpha thalassemia, a deadly condition, each year.
Many different problems can arise during pregnancy, but few are more deadly than a condition called alpha thalassemia, a blood disorder that is fatal to the fetus. However, that is changing due to a new treatment involving stem cells. Still in the clinical trial phase, the treatment recently saved the life of an infant named Elianna and has the potential to save hundreds more.
Elliot Vichinsky, MD, founder of the Northern California Comprehensive Thalassemia Center at UCSF Benioff Children’s Hospital in Oakland, states, “Once universally fatal, thalassemia can not be managed as a chronic disease…In utero stem cell transplantation may take it one step further: as a disease that can be successfully treated before birth.”
According to the National Institutes of Health, alpha thalassemia drastically reduces production of hemoglobin in the body. Hemoglobin is a protein found in red blood cells and without it, red blood cells are unable to carry enough oxygen to the rest of the body. Without enough hemoglobin, the body becomes anemic, causing weakness, fatigue, and other complications. In a fetus, it can also cause enlarged organs and life-threatening swelling.
There are two forms of alpha thalassemia called HbH disease and Hb Bart syndrome. HbH is the milder of the two and can cause anemia that is more moderate than Hb Bart, along with jaundice, an overgrowth of bone in the the upper jaw and forehead, and hepatosplenomegaly, which is an enlargement of the spleen and liver. HbH often isn’t detectable until early childhood. Those afflicted normally live into adulthood.
The other form of alpha thalassemia, Hb Bart syndrome, is the much more deadly of the two types. Symptoms of Hb Bart include severe anemia, hepatosplenomegaly, and defects of the heart, urinary system, and genitalia. Hb Bart also often causes hydrops fetalis, a condition that causes large amounts of fluid to build up in at least two areas of a fetus or newborn’s body. The Hb Bart form of alpha thalassemia is often deadly, causing stillbirth or death shortly after birth.
Alpha thalassemia is a genetic mutation “in the DNA of cells that make hemoglobin.” Approximately five percent of the world population are carriers of this mutation and thousands of children are born with the condition every year. Inheriting the gene is complex and involve both the HBA1 and HBA2 genes. There are two copies, called alleles, of each of the genes in cells, meaning that there are four alleles in each cell that produce the protein alpha-globin. A child inherits one HBA1 and one HBA2 allele from each of their biological parents. A fetus gets alpha thalassemia when one or more of these genes are missing from their genetic makeup.
The severity of alpha thalassemia depends on how many missing genes there are between the two parents. For example, if each parent is missing at least one alpha-globin allele, every child they have has the potential to develop alpha thalassemia. The National Institutes of Health state that “the precise risk depends on how many alleles are missing and which combination of HBA1 and HBA2 genes is affected.” In many cases, if a person has:
- one mutated allele, they are will be a carrier but probably won’t display signs of alpha thalassemia.
- two mutated alleles, they will probably have mild symptoms. This is called alpha thalassemia minor.
- three mutated alleles, they will have “moderate to severe” symptoms. This is HbH disease.
- four mutated alleles, they will develop the most severe form of the condition, alpha thalassemia major, and will likely not survive birth or live long after birth.
Risk factors for alpha thalassemia include a family history of the disease, along with African, Southeast Asian, Central Asian, Indian, Middle Eastern, and Mediterranean ancestry. The Mayo Clinics says that alpha thalassemia is almost impossible to prevent and recommends genetic testing if you either have thalassemia or suspect you carry the gene.
Johns Hopkins states that a fetus can be diagnosed by a prenatal text call chorionic villus sampling (CVS), which is performed by taking a tissue sample from the placenta to “test for chromosomal abnormalities and certain other genetic problems.” Amniocentesis, which involves testing a sample of amniotic fluid, can also be used to look for alpha thalassemia.
Treatment for alpha thalassemia traditionally involved giving fetuses blood transfusions beginning in the second trimester. If the child survives, monthly blood transfusions are needed for the rest of their life. A less common treatment is iron chelation therapy, which “removes iron from the body caused by repeated blood transfusions.”
Bone-marrow transplants are the only current cure for alpha thalassemia, but it is difficult to find a donor match and the procedure itself is risky. The doctor that performed baby Elianna’s surgery, Tippi MacKenzie, is the Associate Professor of Surgery and Director of Research at the UCSF Fetal Treatment Center. She says that waiting until a child is born brings additional complications. She says, “If you do the stem cell transplant after birth, you have to give the baby a lot of toxic medicines to make room in the bone marrow, and that can cause diseases on its own.” One of the toxic medicines MacKenzie references is chemotherapy, one of the current treatments for cancer.
Elianna’s treatment began with blood transfusions in utero. However, one of the transfusions also contained extracted bone marrow from her mother. A fetus is “more tolerant of its mother’s cells than [cells from] a living baby, which means that doctors don’t have to worry about rejection of the transplant.
Elianna was born at week 37, nearly full term, and weighed five pounds. While it is still too soon to tell if she has been cured of alpha thalassemia, doctors are optimistic. The injection of the pregnant parent’s bone marrow could potentially save thousands of lives each year. Dr. Vichinsky believes that this trial may lead lead to future treatments for beta thalassemia, sickle-cell anemia, another often deadly blood disease, and other life-threatening conditions.