Infections in Infants with SCID: Isolation, Infection Screening, and Prophylaxis in PIDTC Centers

Morna J Dorsey; Nicola A M Wright; Natalia S Chaimowitz; Blachy J Dávila Saldaña; Holly Miller; Michael D Keller; Monica S Thakar; Ami J Shah; Rolla Abu-Arja; Jeffrey Andolina; Victor Aquino; J L Barnum; Jeffrey J Bednarski; Monica Bhatia; Francisco A Bonilla; Manish J Butte; Nancy J Bunin; Sharat Chandra; Sonali Chaudhury; Karin Chen; Hey Chong; Geoffrey D E Cuvelier; Jignesh Dalal; Magee L DeFelice; Kenneth B DeSantes; Lisa R Forbes; Alfred Gillio; Fred Goldman; Avni Y Joshi; Neena Kapoor; Alan P Knutsen; 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; Lolie C Yu; Morton J Cowan; Rebecca H Buckley; Christopher C Dvorak; Linda M Griffith; Elie Haddad; Donald B Kohn; Brent Logan; Luigi D Notarangelo; Sung-Yun Pai; Jennifer Puck; Michael A Pulsipher; Jennifer Heimall

doi:10.1007/s10875-020-00865-9

Infections in Infants with SCID: Isolation, Infection Screening, and Prophylaxis in PIDTC Centers

J Clin Immunol. 2021 Jan;41(1):38-50. doi: 10.1007/s10875-020-00865-9. Epub 2020 Oct 2.

Authors

Morna J Dorsey¹, Nicola A M Wright², Natalia S Chaimowitz³, Blachy J Dávila Saldaña^{4

5}, Holly Miller⁶, Michael D Keller⁷, Monica S Thakar⁸, Ami J Shah⁹, Rolla Abu-Arja¹⁰, Jeffrey Andolina¹¹, Victor Aquino¹², J L Barnum¹³, Jeffrey J Bednarski¹⁴, Monica Bhatia¹⁵, Francisco A Bonilla¹⁶, Manish J Butte¹⁷, Nancy J Bunin¹⁸, Sharat Chandra^{19

20}, Sonali Chaudhury²¹, Karin Chen²², Hey Chong¹³, Geoffrey D E Cuvelier²³, Jignesh Dalal²⁴, Magee L DeFelice²⁵, Kenneth B DeSantes²⁶, Lisa R Forbes²⁷, Alfred Gillio²⁸, Fred Goldman²⁹, Avni Y Joshi³⁰, Neena Kapoor³¹, Alan P Knutsen³², Lisa Kobrynski³³, Jay A Lieberman³⁴, Jennifer W Leiding^{35

36}, Benjamin Oshrine³⁶, Kiran P Patel³⁷, Susan Prockop³⁸, Troy C Quigg³⁹, Ralph Quinones⁴⁰, Kirk R Schultz⁴¹, Christine Seroogy⁴², David Shyr^{43

44}, Subhadra Siegel⁴⁵, Angela R Smith⁴⁶, Troy R Torgerson⁸, Mark T Vander Lugt⁴⁷, Lolie C Yu⁴⁸, Morton J Cowan¹, Rebecca H Buckley⁴⁹, Christopher C Dvorak¹, Linda M Griffith⁵⁰, Elie Haddad⁵¹, Donald B Kohn⁵², Brent Logan⁵³, Luigi D Notarangelo⁵⁴, Sung-Yun Pai^{55

56}, Jennifer Puck¹, Michael A Pulsipher³¹, Jennifer Heimall⁵⁷

Affiliations

¹ Division of Pediatric Allergy, Immunology, & Bone Marrow Transplant, Benioff Children's Hospital, University of California San Francisco, San Francisco, CA, USA.
² Division of Hematology/Immunology, Department of Pediatrics, Alberta Children's Hospital, University of Calgary, Calgary, AB, Canada.
³ Section of Immunology, Allergy and Retrovirology, Department of Pediatrics, William T. Shearer Center for Human Immunobiology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.
⁴ Division of Blood and Marrow Transplantation, Children's National Medical Center, Washington, DC, USA.
⁵ Department of Pediatrics, George Washington University, Washington, DC, USA.
⁶ Center for Cancer and Blood Disorders, Phoenix Children's Hospital, Phoenix, AZ, USA.
⁷ Division of Allergy & Immunology, Children's National Health System, and Division of Pediatrics, George Washington University, Washington, DC, USA.
⁸ Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, USA.
⁹ Division of Stem Cell Transplantation and Regenerative Medicine, Lucille Packard Children's Hospital, Stanford School of Medicine, Stanford, CA, USA.
¹⁰ Nationwide Children's Hospital, Columbus, OH, USA.
¹¹ Department of Pediatrics, Golisano Children's Hospital, University of Rochester Medical Center, Rochester, NY, USA.
¹² University of Texas, Southwestern, Dallas, TX, USA.
¹³ UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
¹⁴ Department of Pediatrics, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.
¹⁵ Pediatric Stem Cell Transplant Columbia, University Irving Medical Center, New York, NY, USA.
¹⁶ Northeast Allergy, Asthma & Immunology (private practice), Leominster, MA, USA.
¹⁷ Division of Immunology, Allergy, and Rheumatology, Department of Pediatrics, University of California Los Angeles, Los Angeles, CA, USA.
¹⁸ Cellular Therapy and Transplant Section, Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
¹⁹ Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
²⁰ Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
²¹ Division of Pediatric Hematology, Oncology, Stem Cell Transplantation, Ann & Robert H Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
²² Division of Allergy and Immunology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA.
²³ Pediatric Blood and Marrow Transplant Program, CancerCare Manitoba, Department of Pediatrics and Child Health, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
²⁴ Pediatric Bone Marrow Transplant, Rainbow Babies and Children's Hospital, Cleveland, OH, USA.
²⁵ Division of Allergy and Immunology, Nemours/AI duPont Hospital for Children, Wilmington, DE, USA.
²⁶ Division of Hematology, Oncology and Bone Marrow Transplant, Department of Pediatrics, University of Wisconsin School of Medicine, Madison, WI, USA.
²⁷ William T Shearer Center for Human Immunobiology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.
²⁸ Joseph M Sanzari's Childrens Hospital, Hackensack University Medical Center, Hackensack, NJ, USA.
²⁹ Department of Pediatrics, Division of Hematology Oncology, University of Alabama at Birmingham, Birmingham, AL, USA.
³⁰ Pediatric and Adult Allergy/Immunology, Mayo Clinic, Rochester, MN, USA.
³¹ Section of Transplantation and Cellular Therapy, Children's Hospital Los Angeles Cancer and Blood Diseases Institute, USC Keck School of Medicine, Los Angeles, CA, USA.
³² Pediatric Allergy and Immunology, Cardinal Glennon Children's Hospital, St. Louis, MO, USA.
³³ Children's Healthcare of Atlanta, Emory University Department of Pediatrics, Allergy and Immunology, Atlanta, GA, USA.
³⁴ Department of Pediatrics, The University of Tennessee Health Science Center, Memphis, TN, USA.
³⁵ Division of Allergy and Immunology, Department of Pediatrics, University of South Florida, St. Petersburg, FL, USA.
³⁶ Johns Hopkins All Children's Hospital, Cancer and Blood Disorders Institute, St. Petersburg, FL, USA.
³⁷ Children's Healthcare of Atlanta, Atlanta, GA, USA.
³⁸ Department of Pediatrics, Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
³⁹ Pediatric Blood and Marrow Transplantation Program, Methodist Children's Hospital, San Antonio, TX, USA.
⁴⁰ Pediatric Hematology, Oncology and Bone Marrow Transplant, Children's Hospital Colorado, Aurora, CO, USA.
⁴¹ Michael Cuccione Childhood Cancer Research Program, BC Children's Hospital and Research Institute, Vancouver, British Columbia, Canada.
⁴² University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
⁴³ Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Utah School of Medicine, Primary Children's Hospital, Salt Lake City, UT, USA.
⁴⁴ Division of Stem Cell Transplant, Department of Pediatrics, Stanford Medicine, Lucile Packard Children's Hospital, Palo Alto, CA, USA.
⁴⁵ Division of Pediatric Pulmonology, Allergy and Immunology and Sleep Medicine, Westchester Medical Center, Valhalla, NY, USA.
⁴⁶ Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN, USA.
⁴⁷ Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, MI, USA.
⁴⁸ Division of Heme-Onc/HSCT, Children's Hospital/LSUHSC, New Orleans, LA, USA.
⁴⁹ Division of Allergy and Immunology, Department of Pediatrics and Department of Immunology, Duke University School of Medicine, Durham, NC, USA.
⁵⁰ Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
⁵¹ Pediatric Immunology and Rheumatology Division, CHU Sainte-Justine, Department of Pediatrics, Department of Microbiology, Immunology and Infectious Disease, University of Montreal, Montreal, QC, Canada.
⁵² Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
⁵³ Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA.
⁵⁴ Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
⁵⁵ Division of Hematology-Oncology, Boston Children's Hospital, Boston, MA, USA.
⁵⁶ Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
⁵⁷ Division of Allergy and Immunology, Children's Hospital of Philadelphia, Wood 3301, 3401 Civic Center Blvd, Philadelphia, PA, 19104, USA. [email protected].

Abstract

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.

Keywords: Infections; hematopoietic stem cell transplant; newborn screening; primary immunodeficiency; prophylaxis; severe combined immunodeficiency.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Age of Onset
Antibiotic Prophylaxis
Clinical Decision-Making
Disease Management
Disease Susceptibility
Female
Hematopoietic Stem Cell Transplantation / adverse effects
Hematopoietic Stem Cell Transplantation / methods
Humans
Infant
Infant, Newborn
Infection Control*
Infections / diagnosis
Infections / epidemiology*
Infections / etiology*
Male
Neonatal Screening
Prognosis
Public Health Surveillance
Severe Combined Immunodeficiency / complications*
Severe Combined Immunodeficiency / diagnosis
Severe Combined Immunodeficiency / epidemiology*
Severe Combined Immunodeficiency / therapy
Surveys and Questionnaires
Time-to-Treatment

Associated data

ClinicalTrials.gov/NCT01186913

Abstract

Publication types

MeSH terms

Associated data

Grants and funding