Purpose: The Primary Immune Deficiency Treatment Consortium (PIDTC) enrolled children with severe combined immunodeficiency (SCID) in a prospective natural history study of hematopoietic stem cell transplant (HSCT) outcomes over the last decade. Despite newborn screening (NBS) for SCID, infections occurred prior to HSCT. This study’s objectives were to define the types and timing of infection prior to HSCT in patients diagnosed via NBS or by family history (FH) and to understand the breadth of strategies employed at PIDTC centers for infection prevention. Methods: We analyzed retrospective data on infections and pre-transplant management in patients with SCID diagnosed by NBS and/or FH and treated with HSCT between 2010 and 2014. PIDTC centers were surveyed in 2018 to understand their practices and protocols for pre-HSCT management. Results: Infections were more common in patients diagnosed via NBS (55%) versus those diagnosed via FH (19%) (p = 0.012). Outpatient versus inpatient management did not impact infections (47% vs 35%, respectively; p = 0.423). There was no consensus among PIDTC survey respondents as to the best setting (inpatient vs outpatient) for pre-HSCT management. While isolation practices varied, immunoglobulin replacement and antimicrobial prophylaxis were more uniformly implemented. Conclusion: Infants with SCID diagnosed due to FH had lower rates of infection and proceeded to HSCT more quickly than did those diagnosed via NBS. Pre-HSCT management practices were highly variable between centers, although uses of prophylaxis and immunoglobulin support were more consistent. This study demonstrates a critical need for development of evidence-based guidelines for the pre-HSCT management of infants with SCID following an abnormal NBS. Trial Registration: NCT01186913.
Bibliographical noteFunding Information:
Memoriam: The authors recognize the late Dr. William T. Shearer for his contribution to this and many studies of the PIDTC. We thank Catherine Chang, Tara Bani, and Elizabeth Dunn for project management and assistance. ? Morna Dorsey, Nicola AM Wright, Natalia S. Chaimowitz, Blachy J D?vila Salda?a, Holly Miller, Michael D. Keller, Monica S. Thakar, and Ami J. Shah, MD, designed data collection instruments, collected data, carried out the initial analyses, drafted the initial manuscript, and reviewed and revised the final manuscript. ? Morton J Cowan, Rebecca H. Buckley, Christopher C. Dvorak, Elie Haddad, Donald B. Kohn, Luigi D. Notarangelo, Sung Yun Pai, Jennifer Puck, MD, Michael Pulsipher, and Jennifer Heimall conceptualized and designed the study, designed the data collection instruments, collected data, carried out the initial analyses, drafted the initial manuscript, and reviewed and revised the manuscript. ? Linda Griffith and Brent Logan conceptualized and designed the study, designed the data collection instruments, carried out data analyses, and reviewed and revised the manuscript. ? Rolla Abu-Arja, Jeffrey Andolina, Victor Aquino, JL Barnum, Jeffrey J. Bednarski, Monica Bhatia, Francisco A. Bonilla, Manish J. Butte, Nancy J Bunin, Sharat Chandra, Sonali Chaudhury, Karin Chen, Hey Chong, Geoff Cuvelier, MD, FRCPC, Jignesh Dalal, Magee L. DeFelice, Kenneth B. DeSantes, Lisa R Forbes, Alfred Gillio, Fred Goldman, Avni Y Joshi, Neena Kapoor, MD, Alan P. Knutsen, MD, Lisa Kobrynski, Jay A Lieberman, Jennifer W Leiding, Benjamin Oshrine, Kiran P. Patel, Susan Prockop, Troy C. Quigg, Ralph Quinones, Kirk R. Schultz, Christine Seroogy, David Shyr, Subhadra Siegel, Angela R. Smith, Troy R. Torgerson, Mark T. Vander Lugt, and Lolie C Yu collected data and critically reviewed the manuscript for important intellectual content. ? All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
This work was supported by the Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases (NIAID); and the Office of Rare Diseases Research (ORDR), National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), Bethesda, MD; Public Health Service grant/cooperative agreements U54-AI082973 (PIs: MJ Cowan; September 2019 forward JM Puck and DB Kohn), U54-NS064808 and U01-TR001263 (PI: JP Krischer), R13-AI094943 (PIs: MJ Cowan; March 2018 forward JM Puck), and the Division of Intramural Research, NIAID, NIH. LD Notarangelo is supported by the Division of Intramural Research, NIAID, NIH. The PIDTC is a part of the Rare Diseases Clinical Research Network (RDCRN) of ORDR, NCATS. Collaborative work of the PIDTC with the Pediatric Blood and Marrow Transplant Consortium (PBMTC) is supported by the U54 grants above along with support of the PBMTC Operations Center by grant/cooperative agreement U10HL069254 (PI: MA Pulsipher, NHLBI/NCI) and a Johnny Cristopher Children’s Charitable Foundation St. Baldrick’s Consortium Grant. Collaborative work of the PIDTC with the Center for International Blood and Marrow Transplant Research (CIBMTR) is supported by grant/cooperative agreement U24-CA76518 (PI: MM Horowitz) from the National Cancer Institute (NCI), NHLBI, and NIAID, NIH; and grant/cooperative agreement U01HL069294 from the NHLBI and NCI; contract HHSH250201200016C and HHSH234200637015C with the Health Resources and Services Administration (HRSA/DHHS); and grants N00014-13-1-0039 and N00014-14-1-0028 from the Office of Naval Research. Acknowledgments Authorship Contributions
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- hematopoietic stem cell transplant
- newborn screening
- primary immunodeficiency
- severe combined immunodeficiency