Survival rates improve among infants with severe combined immunodeficiency screenings
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Key takeaways:
- Infants are screened in all 50 states and in four provinces in Canada.
- Despite advances, the type of transplant did not impact survival rates.
- Age at time of transplant and infection history drove improvements.
Five-year survival rates among children with severe combined immunodeficiency remained stable at 72% to 73% from 1982 to 2009 before improving to 87% from 2010 to 2018, according to a study published in The Lancet.
Newborn screening for severe combined immunodeficiency (SCID) began in the United States in 2008 and in Canada in 2013, facilitating early diagnosis and hematopoietic cell transplantation (HCT), Morton J. Cowan, MD, pediatric immunologist at UCSF Benioff Children’s Hospital and medical director of the UCSF Pediatric Cell Therapy Laboratory, and colleagues wrote.
The study analyzed data from 902 children with SCID treated with allogeneic HCT at 34 Primary Immune Deficiency Treatment Consortium sites in the United States and Canada based on intervals including 1982-1989, 1990-1999, 2000-2009 and 2010-2018.
The researchers singled 2010-2018 out as the era of newborn screening initiation and expansion. Since the end of 2020, all 50 states in the U.S. and four provinces in Canada have been screening newborns for SCID.
“The findings are highly significant, since they are the first to definitively demonstrate the importance of newborn screening for SCID in terms of survival,” Cowan told Healio.
When infants received HCT from sibling donors matched for human leukocyte antigens (HLA), overall survival rates remained high and unchanged between the four study periods, ranging from 92% to 100%.
When these infants were excluded from analysis and the study focused on infants who received HCT from other sources, 5-year survival rates held steady at 72% to 73% from 1982 to 2009, even though there were advances in clinical care. Five-year survival rates then increased to 87% for the 2010-2018 study period.
Overall 5-year survival rates since 2010 included 92.5% (95% CI, 85.8%-96.1%) for children whose SCID was identified via newborn screening, 79.9% (95% CI, 69.5%-87%) for children whose SCID was identified by clinical illness and 85.4% (95% CI, 71.8%-92.8%) for children whose SCID was identified by family history (P = .043).
Using multivariable analysis, the researchers also found associations between lower overall survival across all four study periods and active infection (HR = 2.41; 95% CI, 1.56-3.72), age 3.5 months and older at HCT (HR = 2.12; 95% CI, 1.38-3.24) and Black or African-American race (HR = 2.33; 95% CI, 1.56-3.46), as well as with certain SCID genotypes.
Additional adjustments further found that type of HCT did not confer a survival advantage after 2010 compared with earlier study periods (HR = 0.73; 95% CI, 0.43-1.26). Instead, younger age and freedom from infections at HCT, both directly driven by newborn screening, drove the improvements in overall survival, the researchers said.
With median ages of 193 to 187 days, age at HCT also was stable from 1982 to 2009. But between 2010 and 2018, the median age at HCT was 111 days (P < .0001), and patients with typical SCID had a median age at HCT of 94 days (P < .0001).
Between 1982 and 1989, 59% of patients received HCT while they had active infections. Between 2010 and 2018, however, that number fell to 31%. Similarly, 18% of patients between 1982 and 1989 and 49% of patients between 2010 and 2018 did not have any previous history of infections when they received HCT.
Based on these findings, the researchers attributed improvements in survival among infants with SCID since 2010 to newborn screenings for the disease. Also, the researchers said, these findings may support global health efforts to expand newborn screenings for SCID around the world.
“These findings represent our own experience, and they are important for other countries that may not be considering newborn screenings for SCID and want proof,” Cowan said.
The researchers plan on continuing their work.
“The next step is our ongoing prospective study of newly diagnosed SCID in which we are focused on identifying factors that can further improve the outcome for these patients since even with newborn screenings, some will get infected,” Cowan said.
Reference:
- Screening newborns for deadly immune disease saves lives. https://www.niaid.nih.gov/news-events/screening-newborns-deadly-immune-disease-saves-lives. Published June 20, 2023. Accessed June 23, 2023.
For more information:
Morton J. Cowan, MD, can be reached at mort.cowan@ucsf.edu.