Newborn Elianna was the first patient enrolled in the world’s first clinical trial using blood stem cells transplanted prior to birth. The infant had been critically ill during the second trimester of pregnancy due to a commonly fatal disease called alpha thalassemia. Her parents, Nichelle Obar and Chris Constantino, were unknowingly carriers of the disease. Typically, a baby with this problem dies before they’re even born. Not Elianna! She was born at UCSF Medical Center at Mission Bay in February, four months after undergoing the transplant to treat the blood disorder.
This phase 1 trial aimed to determine first whether the procedure – which includes infusing the mother’s stem cells along with several blood transfusions – would be safe. The ultimate goal, however, will be to assess whether the mother’s stem cells integrate, or engraft, in the fetus’ bone marrow and generate healthy blood cells throughout the child’s life.
A lot of the time, women whose fetuses are diagnosed with alpha thalassemia terminate the pregnancy due to the low likelihood of a successful birth. This clinical trial with Elianna is a great hope. Tippi MacKenzie, MD, a pediatric and fetal surgeon at UCSF Benioff Children’s Hospital San Francisco, who performed the pioneering transplant after a decade of research, said:
“We are encouraged by how well she and her mother have tolerated this complex treatment. Her birth suggests that fetal therapy, including fetal transfusions, is a viable option to offer to families with this diagnosis.”
Elianna was born at 37 weeks’ gestation, weighing just under 5 lbs. She has been discharged from the hospital and has returned with her family to their home in Hawaii. However, she will require further blood transfusions or another stem cell transplant to remain healthy.
Diagnosis, Transfusion, Transplantation
It all began when a visit to the medical center near the family’s hometown detected life-threatening swelling, or hydrops, during an ultrasound. The swelling, which included an enlarged heart, was the result of the body’s response to severe anemia and lack of oxygen – the hallmark of alpha thalassemia major and the most dangerous variant of the disease. After this, MacKenzie’s team at the UCSF Fetal Treatment Center treated the fetus with regular in-utero blood transfusions throughout the pregnancy.
Juan Gonzalez Velez, MD, Ph.D., an obstetrician/gynecologist at the UCSF Division of Maternal-Fetal Medicine, who performed the transfusions, said:
“Intrauterine blood transfusions were needed to treat the hydrops before the stem cell transplant could be performed. During the last 30 years, this has been the treatment of choice for patients developing severe fetal anemia and we think that fetuses with alpha thalassemia can also benefit from these transfusions.”
With each transfusion during the pregnancy, the fetus’ poor prognosis improved slowly. The stem cell transplant took place during one of those transfusions. In utero, stem cell transplantation involves extracting bone marrow from the pregnant woman between the 18th to 25th week of pregnancy.
The bone marrow cells are processed, and hematopoietic cells – immature stem cells that can evolve into all types of blood cells – are singled out from the mix. They are then injected through the woman’s abdomen into the umbilical vein of the fetus, where they can circulate through the bloodstream, developing into healthy, mature blood cells.
Conclusion
This specific trial aimed to assess the safety of the procedure, not its effectiveness; the baby survived but was not cured. Future plans may include using in-utero stem cells to treat beta-thalassemia, the more common type of the disease, as well as sickle cell anemia and other serious and life-threatening genetic disorders.
Elliott Vichinsky, MD, who is overseeing the baby’s treatment and is the founder of the Northern California Comprehensive Thalassemia Center at UCSF Benioff Children’s Hospital Oakland, said:
“Once universally fatal, thalassemia can now 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.”
