Early transplantation of blood-forming stem cells is a highly effective treatment for infants with severe combined immunodeficiency (SCID), a group of rare, life-threatening inheritedc, a study funded by the National Institutes of Health suggests.

Approximately three-quarters of SCID infants who received transplants survived for at least five years. Infants who received transplants within the first 3.5 months of life had the best outcomes. Researchers from the Primary Immune Deficiency Treatment Consortium External Web Site Policy (PIDTC), funded by NIH’s National Institute of Allergy and Infectious Diseases (NIAID), report their findings in the July 31 issue of the New England Journal of Medicine.

SCID is caused by defects in genes involved in the development and function of infection-fighting T and B cells. Infants with SCID appear healthy at birth but are highly susceptible to infections. If untreated, SCID is fatal, usually within the first year of life. Development of a newborn screening test has made it possible to detect SCID before symptoms appear. The test was added to the US Department of Health and Human Services’ Recommended Uniform Screening Panel External Web Site Policy for newborns in 2010, but to date, only 21 states External Web Site Policy have implemented newborn screening for SCID.

“The findings from this study highlight the positive impact of treating SCID early in life,” said NIAID director Anthony S. Fauci, M.D. “They also suggest that widespread use of newborn screening tests for SCID is warranted to ensure that infants with this rare syndrome receive life-saving transplants.”

Stem cell transplantation can fully correct the T-cell and, less consistently, the B-cell deficiencies of SCID infants. To identify factors that contribute to successful transplant outcomes, PIDTC investigators analysed data from 240 SCID infants who received transplants at 25 clinical centres across the United States and Canada between 2000 and 2009.

The researchers found that younger infants and those without infections had excellent survival rates. Almost all 68 babies transplanted within the first 3.5 months of life survived, with 64 still alive five years after transplant. Many of these babies had a family history of SCID and were diagnosed before the onset of infections. Survival rates for older infants who never had infection or whose infections cleared before transplant also were high 90 per cent and 82 per cent, respectively. Only 50 per cent of babies who had infections at the time of transplant survived for five years.

“These findings indicate that early transplantation and absence of infection are critical to achieving the best transplant outcomes for infants with this serious disorder,” said Daniel Rotrosen, M.D., director of NIAID’s Division of Allergy, Immunology and Transplantation. “The results of this study pave the way for further work to identify optimal stem cell transplant procedures for infants with SCID.”

Donor type also affected transplant success, with the best outcomes resulting from sibling donors whose human leukocyte antigens (HLA) proteins that help regulate immune responses matched those of the recipient. HLA matching reduces the risk of graft-versus-host disease, in which transplanted cells attack the recipient’s cells. Because HLA markers are inherited from both parents, siblings have a one-in-four chance of being a perfect match.  In the PIDTC study, 97 per cent of infants who received transplants from HLA-matched siblings survived at least five years.

Regardless of donor type, survival rates were high for infants transplanted within the first 3.5 months of life and those of any age without infection at time of transplant. SCID infants with active infection and lacking a matched sibling donor did not fare as well. These infants were most likely to survive if they received specially treated c from a parent, but did not receive any pre-transplant chemotherapy, which often is administered to help the transplanted cells survive. This finding indicates that treatment and prevention of infection and avoidance of chemotherapy if an infection cannot be cleared are important considerations before transplantation.

Transplants from matched siblings led to the best restoration of immune function. Among survivors of transplants from non-sibling donors, use of certain pre-transplant chemotherapy regimens was associated with higher T-cell numbers and more consistent B-cell function. However, chemotherapy carries the risk of severe early side effects, which can reduce chances of survival. Survivors may experience long-term chemotherapy side effects, such as poor growth. Future research will focus on developing transplant procedures that improve survival and immune recovery while avoiding harmful side effects.

This work was supported by NIAID, NIH, under grant numbers 1U54AI082973 and R13AI094943, and by the NIH Office of Rare Diseases Research, National Center for Advancing Translational Sciences. The National Heart, Lung and Blood Institute, part of NIH; the St. Baldrick’s Foundation; and the David Center of Texas Children’s Hospital also provided funding.

NIAID conducts and supports research at NIH, throughout the United States, and worldwide to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses.