UCSF performs first-ever transplant in a fetus
The tiniest patient — still inside her mother’s womb — has been treated with a stem cell transplant derived from her mother’s bone marrow, at UC San Francisco.
The infant is the first patient in the world to receive blood-making stem cells prior to birth, according to the university.
Most stem cell transplants are performed far later in life to treat diseases such as cancer.
But this patient, identified as Elianna Constantino of Hawaii, was treated about four months before her birth. She received the transplant from her mother, so did not reject it.
She suffered from a lethal form of alpha thalassemia, a disease caused by a gene carried by nearly 5 percent of the world’s population. Most fetuses with this condition die before birth. It restricts the blood’s ability to carry oxygen to vital organs.
It is too early to say if it will save her life.
But she tolerated the treatment and was born healthy on Feb. 1, giving hope for fetal treatment of other patients, according to Dr. Tippi MacKenzie, who performed the pioneering transplant after decades of research.
“Her healthy birth suggests that fetal therapy is a viable option to offer to families with this diagnosis,” said MacKenzie, a pediatric and fetal surgeon at UCSF Benioff Children’s Hospital San Francisco, in a prepared statement.
In the future, it could be tested in fetuses suffering from sickle cell anemia, hemophilia and other hereditary blood disorders.
The success of the procedure hinges on this insight: The fetus’s immune system is underdeveloped, so it can tolerate the mother’s cells during pregnancy, not rejecting them.
Once a person is born, such transplants require aggressive immune-suppressant treatment.
Alpha thalassemia is a genetic disease most common in people from China, the Philippines, Thailand, India and the Middle East — parts of the globe where many Americans, especially those in the San Francisco Bay Area, claim their ancestry.
In most patients, progressive anemia and heart failure develop before birth, causing developmental impairment if treatment is delayed. Treatment includes lifelong blood transfusions starting in the second trimester, followed by further transfusions after birth, or a bone-marrow transplant with a matched donor in childhood. In most cases, the fetus dies in utero or the pregnancy is aborted due to lack of treatment options.
Stem cell transplants from a matched donor in childhood are successful in some cases, but patients face risks, including graft-versus-host disease and serious side effects from immune-suppression drugs.
Parents Nichelle Obar, 40, and Chris Constantino, 37, did not learn until the pregnancy that they are thalassemia carriers. Their first child, who is now 3, is healthy.
They came to UCSF after an ultrasound performed at a medical center near their hometown detected Elianna had an enlarged heart, the result of the body’s response to severe anemia and lack of oxygen — and the hallmark of the most dangerous form of alpha thalassemia.
Obar was 21 weeks pregnant, but her fetus was deteriorating.
Almost immediately, doctors gave Elianna a transfusion, which improved her health.
Then bone marrow was collected from her mother. These bone marrow cells were processed and hematopoietic cells — immature stem cells that can evolve into all types of blood cells — were isolated from the mix.
They were injected through Obar’s abdomen into the umbilical vein of Elianna, where they started circulating through the bloodstream, maturing into healthy blood cells.
The infant was born at 37 weeks’ gestation, weighing just under 5 pounds. She has been discharged from the hospital and has returned with her family to their home in Hawaii.
“It is too early to say how effective the stem cell transplantation will be, but we are encouraged by how well she and her mother have tolerated the treatment,” MacKenzie said.
The procedure is part of a clinical study at UCSF Benioff Children’s Hospitals in San Francisco and Oakland. The two hospitals are enrolling 10 pregnant women in the first phase of a clinical trial to treat fetuses with this inherited disorder.
The trial, the first of its kind in the world, was funded by a $12.1 million grant from the California Institute for Regenerative Medicine.