Six-year-old Paulina Michelle Aguilar made medical history Thursday when she became the first recipient of a bone marrow transplant to also serve as the donor in a second transplant, in this case to her 5-week-old sister.
Paulina was born with severe combined immunodeficiency disease (SCID), a genetic problem that left her vulnerable to fatal infections. SCID is the same disease that afflicted David, the famous "Bubble Boy" in Houston. He died at age 12 in 1984, before marrow transplants became available.
Five years ago, Paulina received a bone marrow transplant from her father that, along with a second, "booster" transplant, cured the disorder.
Thursday, Dr. Stephen Feig at UCLA Medical Center drew bone marrow from Paulina and injected it into her baby sister Tatiana Mari, who also has SCID. Within two to three weeks doctors should know if the unprecedented operation will succeed and cure the younger sister. Dr. E. Richard Stiehm of UCLA said there is a 90% chance it will.
The procedure was "quite a remarkable feat," said Dr. Morton Cowan of UC San Francisco. "It is particularly important for this patient" because using the sister's marrow reduced the risk of the donor cells attacking the recipient's body, which is one of the major causes of death in bone marrow transplants.
"By taking the marrow from the first [daughter] and giving it to the second, there should really not be any risk [of this "graft versus host" disease] to the second one," he added.
Recruiting a bone marrow recipient as a donor will not become a widespread practice, however, said Dr. Rebecca Buckley of Duke University Medical Center, because the number of families in which there are two SCID victims is small. The best solution for the problem, she added, is genetic counseling before SCID babies are conceived.
But the procedure could eventually aid all transplants, Cowan added, by "increasing our knowledge about how cells from one individual learn to recognize and accept cells from another" without triggering rejection. If that process can be harnessed, it could become possible to do transplants without using anti-rejection drugs.
Paulina's genetic problem was a surprise to her parents, who had no inkling that the gene for SCID was present in their family. It was diagnosed when the girl became critically ill at 3 months with \o7 Pneumocystis\f7 pneumonia, a fatal infection that strikes AIDS victims and others with a compromised immune system. "They gave her 48 hours to live and we hit rock-bottom," said her father, Luis.
She recovered, however, and when she was 7 months old, Stiehm and his colleagues performed a bone marrow transplant using stem cells--the primitive blood cells that are the progenitors of all other cells in the blood--from her father. Such a parental transplant is not as safe as one from a sibling because the parent's blood is not as good an immunological match. Only 50% to 60% of parental transplants are successful, but Paulina was one of the fortunate ones.
Her father's cells, circulating in her bloodstream, provided a missing enzyme required to fight off infections. A second transplant two years later bolstered her immunity, and this year she was able to attend kindergarten. "She is a very healthy girl," Stiehm said.
The Aguilars, who live in Duarte, had a second daughter, Naomi, who was born without the genetic defect. But Tatiana, the third, did have it. Physicians diagnosed the condition at birth, and she has remained in isolation at UCLA since then.
Neither Luis nor Naomi was an acceptable immunological match for Tatiana, so the only potential donor was Paulina, who proved to be a very good match. "The obvious thing to do was to use Paulina as the donor for a transplant, and that was what we did," Stiehm said. With the exception of the standard, minute risk from undergoing anesthesia, the risks to Paulina were small, he said.
"I wasn't worried about Paulina, but about Tatiana," he added.
Now they must wait and see how well she responds to the treatment. "The main thing that determines how well a transplant succeeds is how sick the patient is prior to transplant, and she has been perfectly well," Stiehm said. And, concluded Buckley, "The odds are that this baby is going to do very well."