Measuring the effect of newborn screening on survival after haematopoietic cell transplantation for severe combined immunodeficiency: a 36-year longitudinal study from the Primary Immune Deficiency Treatment Consortium

Monica S. Thakar, University of Washington, Seattle, WA
Brent R. Logan, Medical College of Wisconsin, WI
Jennifer M. Puck, University of California San Francisco, CA
Elizabeth A. Dunn, University of California San Francisco, CA
Rebecca H. Buckley, Duke University Medical Center, Durham, NC
Morton J. Cowan, University of California San Francisco, CA
Richard J. O'Reilly, Memorial Sloan Kettering Cancer Center, New York, NY
Neena Kapoor, Keck School of Medicine, University of Southern California, CA
Lisa Forbes Satter, Baylor College of Medicine, Houston, TX
Sung-Yun Pai, National Cancer Institute (NCI)/NIH, Bethesda, MD
Jennifer Heimall, Perelman School of Medicine at the University of Pennsylvania, PA
Sharat Chandra, University of Cincinnati College of Medicine, Cincinnati, OH
Christen L. Ebens, University of Minnesota, Minneapolis, MN
Deepak Chellapandian, Johns Hopkins University School of Medicine, Baltimore, MD
Olatundun Williams, Columbia University Irving Medical Center, New York, NY
Lauri M. Burroughs, Fred Hutchinson Cancer Center, Seattle, WA
Blachy Davila Saldana, George Washington University School of Medicine and Health Sciences, Washington DC
Ahmad Rayes, University of Utah, Salt Lake City, UT
Lisa M. Madden, Texas Transplant Institute, San Antonio, TX
Shanmuganathan Chandrakasan, Emory University School of Medicine, Atlanta, GA
Jeffrey J. Bednarski II, Washington University School of Medicine, St Louis, MO
Kenneth B. DeSantes, University of Wisconsin, Madison, WI
Geoffrey D. E. Cuvelier, University of Manitoba, Winnipeg, MB
Pierre Teira, University of Montreal, Montreal, QC
Alfred P. Gillio, Hackensack University Medical Center, Hackensack, NJ
Hesham Eissa, University of Colorado, Aurora, CO
Alan P. Knutsen, St Louis University, St Louis, MO
Frederick D. Goldman, University of Alabama, Birmingham, AL
Lolie C. Yu, LSU Health Sciences Center - New OrleansFollow
et al

Document Type

Article

Publication Date

6-20-2023

Publication Title

The Lancet

Abstract

Background: Severe combined immunodeficiency (SCID) is fatal unless durable adaptive immunity is established, most commonly through allogeneic haematopoietic cell transplantation (HCT). The Primary Immune Deficiency Treatment Consortium (PIDTC) explored factors affecting the survival of individuals with SCID over almost four decades, focusing on the effects of population-based newborn screening for SCID that was initiated in 2008 and expanded during 2010–18. Methods: We analysed transplantation-related data from children with SCID treated at 34 PIDTC sites in the USA and Canada, using the calendar time intervals 1982–89, 1990–99, 2000–09, and 2010–18. Categorical variables were compared by χ (2) test and continuous outcomes by the Kruskal-Wallis test. Overall survival was estimated by the Kaplan-Meier method. A multivariable analysis using Cox proportional hazards regression models examined risk factors for HCT outcomes, including the variables of time interval of HCT, infection status and age at HCT, trigger for diagnosis, SCID type and genotype, race and ethnicity of the patient, non-HLA-matched sibling donor type, graft type, GVHD prophylaxis, and conditioning intensity. Findings: For 902 children with confirmed SCID, 5-year overall survival remained unchanged at 72%–73% for 28 years until 2010–18, when it increased to 87% (95% CI 82·1–90·6; n=268; p=0·0005). For children identified as having SCID by newborn screening since 2010, 5-year overall survival was 92·5% (95% CI 85·8–96·1), better than that of children identified by clinical illness or family history in the same interval (79·9% [69·5–87·0] and 85·4% [71·8–92·8], respectively [p=0·043]). Multivariable analysis demonstrated that the factors of active infection (hazard ratio [HR] 2·41, 95% CI 1·56–3·72; p < 0·0001), age 3·5 months or older at HCT (2·12, 1·38–3·24; p=0·001), Black or African-American race (2·33, 1·56–3·46; p < 0·0001), and certain SCID genotypes to be associated with lower overall survival during all time intervals. Moreover, after adjusting for several factors in this multivariable analysis, HCT after 2010 no longer conveyed a survival advantage over earlier time intervals studied (HR 0·73, 95% CI 0·43–1·26; p=0·097). This indicated that younger age and freedom from infections at HCT, both directly driven by newborn screening, were the main drivers for recent improvement in overall survival. Interpretation: Population-based newborn screening has facilitated the identification of infants with SCID early in life, in turn leading to prompt HCT while avoiding infections. Public health programmes worldwide can benefit from this definitive demonstration of the value of newborn screening for SCID. Funding: National Institute of Allergy and Infectious Diseases, Office of Rare Diseases Research, and National Center for Advancing Translational Sciences.

First Page

129

Last Page

140

PubMed ID

37352885

Volume

402

Issue

10396

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