Stem Cell Transplants for SCID Children – Earlier is Better

Severe Combined Immune Deficiency or SCID hamstrings the immune system of newborn children and prevents their immune systems from fighting off any diseases. Children born with SCID must be isolated in a germ-free environment and are sometimes called “bubble children,” since they must go out in the open in space suits that purify their air. However, if children with this “bubble boy” disease have a bone marrow transplant, they can survive. When, however is the best time to give these children such a transplant?

A new study by a research group at the Harvard-affiliated Dana Farber/Boston Children’s Cancer and Blood Disorders Center has reviewed the last ten years of data on treating these young patients. According to the conclusions of this study, children with SCID have the best chance of survival if they undergo a bone marrow stem cell transplant as soon after birth as possible. Consequently, genetic screening of newborn babies for SCID should be expanded, since this disorder leaves affected infants so vulnerable to infection that most die within the first year of life if untreated.

This new research was published in the New England Journal of Medicine, and analyzed data on 240 SCID children who underwent transplants at 25 centers across North America between Jan. 1, 2000, and Dec. 31, 2009 (before the U.S. Department of Health and Human Services recommended newborn screening for SCID in 2010). Currently, 21 states and the District of Columbia, which are home to about two-thirds of all babies born in the United States, screen newborns for SCID. Another nine states are expected to implement newborn screening by the end of 2014.

“The best way to identify patients that early when there is no family history of SCID is through newborn screening,” said Sung-Yun Pai, first author on the study. “Survival is much, much better if infants undergo transplant before they turn 3½ months old and before they contract any SCID-related infections,” said Pai. “The best way to identify patients that early when there is no family history of SCID is through newborn screening.”

While patient age was one of the strongest factors determining the survival of SCID infants, this study also showed that the infection status at the time of transplant and the donor source had the strongest impact on transplant outcomes (i.e., five-year survival and successful immune system reconstitution).

Interestingly, the data used in this study also showed that even though SCID is relatively rare, SCID is twice as common as once thought. “Some children who succumbed to unexplained infections probably suffered from SCID,” Pai noted. SCID is estimated to occur in one of every 50,000 births, up from earlier estimates of one in 100,000.

“Time is not the ally of children with SCID,” said Luigi Notarangelo of Boston Children’s Hospital, who was one of the study’s senior authors. Notarangelo is among those who lobbied successfully to establish SCID newborn screening in Massachusetts in 2009. “Because they do not have a functional immune system, the longer the wait before a transplant, the greater the risk they will contract a potentially devastating infection.”

Children who underwent transplant before 3½ months of age had excellent survival, and this was regardless of donor source or infection status. Likewise, children who underwent transplant with stem cells from a tissue-matched sibling donor. Children outside that age group also had very good survival regardless of donor source, but only if the patient did not have an active infection at the time of transplant. The effect of the donor type and pre-transplant conditioning on survival rates was important only in actively infected patients.

Other findings from this study included:
• 74 percent of the 240 patients studied survived at least five years.
• Among patients who underwent transplant at younger than 3½ months, 94 percent survived.
• Virtually all (97 percent) of the patients who received stem cells from a matched sibling donor survived.
• At 50 percent, survival was lowest among patients who were older than 3½ months and had active infections at the time of transplant. Actively infected infants who did not have a matched sibling donor and who received immunosuppressive or chemotherapy before transplant had particularly poor survival rates (39-53 percent).
• Among patients who never had an infection, 90 percent survived, as did 82 percent of patients whose infection had resolved before transplant.

While survivors who received chemotherapy conditioning had stronger immune systems after transplant, it is still unknown if the drugs used to wipe out the patient’s immune systems before the bone marrow transplant pose a long-term risk when given to such young patients.

“This study accomplishes several things,” she said. “First, it creates a baseline with which to compare patient outcomes since the advent of newborn screening for SCID. Second, it provides guidance for clinicians regarding the use of chemotherapy conditioning before transplantation. Third, it highlights the relative impacts of infection status and patient age on transplant success.

“Lastly, it establishes the importance of early detection and transplantation, which points to the benefit of expanding newborn screening for SCID as broadly as possible.”