In Utero Stem Cell Transplants Could Revolutionize Thalassemia Treatment
An in utero stem cell transplant for a critically ill second-trimester fetus has led to the birth of an apparently healthy infant. The newborn is the first patient enrolled in the world’s first clinical trial using stem cells transplanted prior to birth.
The infant was born at UCSF Benioff Children’s Hospital San Francisco in February, four months after undergoing the transplant to treat a lethal form of thalassemia, a disease caused by a gene carried by nearly 5 percent of the world’s population.
“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,” said Tippi MacKenzie, MD, a pediatric and fetal surgeon at UCSF Benioff Children’s Hospital San Francisco, 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.”
Unique Expertise From UCSF Benioff Children’s Hospitals
The infant, whose parents were unknowingly carriers of the disease, 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.
During pregnancy, MacKenzie’s team at the UCSF Fetal Treatment Center treated the fetus with regular in utero blood transfusions, after a 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, which is the hallmark of alpha thalassemia major, the most dangerous variant of the disease.
“Intrauterine blood transfusions were needed to treat the hydrops before the stem cell transplant could be performed,” said Juan Gonzalez Velez, MD, PhD, an obstetrician/gynecologist at the UCSF Division of Maternal-Fetal Medicine, who performed the transfusions. “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.”
The fetus’s poor prognosis improved slowly with each transfusion during the pregnancy, Gonzalez Velez said. The stem cell transplant took place during one of those transfusions.
The procedure brings together the unique expertise of both UCSF Benioff Children’s Hospitals. The UCSF Fetal Treatment Center, in San Francisco, is the birthplace of fetal surgery and continues to offer life-saving interventions for fetuses with multiple birth defects. UCSF Benioff Children’s Hospital Oakland established its thalassemia program in 1991 to provide multidisciplinary care to the growing number of thalassemia patients. It is an international leader in stem cell and gene therapy for beta thalassemia.
Disease More Common in People from Southeast Asia, India, Middle East
The gene for alpha thalassemia is carried by a significantly higher percentage of people in 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 alpha thalassemia major, 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.
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.
Unlike bone marrow transplants in childhood, the fetus’s immune system is underdeveloped and has a higher tolerance of the mother’s cells during pregnancy, which allows the transplant to take place without aggressive immune-suppressant treatment.
“Once universally fatal, thalassemia can now be managed as a chronic disease,” said 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. “In utero stem-cell transplantation may take it one step further: as a disease that can be successfully treated before birth.”
Vichinsky said that 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.
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