Researchers say Study Underscores Importance of Newborn Screening for “Bubble Boy” Disease
July 31, 2014
from a new study argue for expanding newborn screening for “bubble boy” disease,
which leaves affected infants so vulnerable to infection that most die before
their first birthday if untreated.
Read coverage by the Wall Street Journal, Boston Globe, USA Today and Reuters Health.
Early detection, transplantation provide best outcomes for "bubble boy" disease
Study in NEJM reviews 10 years of data,
argues for expansion of newborn screening
BOSTON (July 31,
2014) — Children born with so-called “bubble boy” disease have the best chance
of survival if they undergo a hematopoietic stem cell transplant as soon after birth
as possible, according to a detailed analysis of 10 years of outcome data by
researchers at Dana-Farber/Boston
Children's Cancer and Blood Disorders Center. These findings, the researchers say,
argue for expanding newborn screening for severe combined immune deficiency (SCID), a disorder that leaves affected infants so vulnerable to infection that
most die within the first year of life if untreated.
The study, published
today in the New England Journal of
Medicine, analyzes data on 240 children with SCID transplanted at 25
centers across North America between Jan. 1, 2000 and Dec. 31, 2009, the decade
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—together 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.
In addition to
patient age, the analysis finds that infection status at the time of transplant
and donor source had the strongest impact on transplant outcomes (i.e.,
five-year survival and successful immune system reconstitution).
is much, much better if infants undergo transplant before they turn 3½ months old
and before they contract any SCID-related infections," says study first
author Sung-Yun Pai, MD, of Dana-Farber/Boston
Children’s. "The best way to identify patients that early when there is no
family history of SCID is through newborn screening."
gained from newborn screening suggest that SCID, while still rare, is twice as
common as once thought. "Some children who succumbed to unexplained
infections probably suffered from SCID," Pai notes. The disorder is now
estimated to occur in one of every 50,000 births, up from earlier estimates of
one in 100,000 births.
is not the ally of children with SCID," says Luigi Notarangelo, MD, of Boston Children's Hospital, one of the study's
senior authors, who was 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."
new study was conducted under the auspices of the Primary Immune Deficiency Treatment Consortium, a North American
collaborative supported by the National Institutes of Health. It looked at the
effect on outcomes of patient age, infection status, donor source, and the use
of chemotherapy to condition patients prior to transplant.
Children who underwent
transplant before 3.5 months of age had excellent survival, regardless of donor
source or infection status, as did patients transplanted with the stem cells of
a matched sibling donor, long recognized as the gold standard of transplant. Children outside that
age group also had very good survival regardless of donor source—sibling, parent
or unrelated donor—as long as the patient did not have an active infection at
the time of transplant. The effect on survival of
donor type and pre-transplant conditioning was only discernible in
actively infected patients.
74 percent of the 240 patients studied survived at least five years.
patients transplanted younger than 3.5 months, 94 percent survived.
all (97 percent) of patients who received stem cells from a matched sibling
50 percent, survival was lowest among patients who were older than 3.5 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 prior to transplant had particularly poor survival (39-53%).
patients who never had an infection, 90 percent survived, as did 82 percent of
patients whose infection had resolved before transplant.
survivors who received chemotherapy conditioning have stronger immune systems
after transplant, further research is needed, Pai says, to determine whether the
late effects of chemotherapy or the vulnerabilities of a weaker immune system pose
the greater long-term risk.
study accomplishes several things," Pai notes. "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.
she adds, "it establishes the importance of early detection and
transplantation, which points to the benefit of expanding newborn screening for
SCID as broadly as possible."
study was supported by the National Institute of Allergy and Infectious Diseases
(grant number 1U54AI082973), the Office of Rare Diseases Research of the
National Center for Advancing Translational Sciences (grant number R13AI094943),
the Translational Research Program of Boston Children’s Hospital, the National
Heart, Lung and Blood Institute (grant numbers K23HL085288, P01HL36444 and 2U01HL069254),
the National Cancer Institute (grant number CA23766), Texas Children's Hospital
and the St. Baldrick's Foundation.