The natural history of children with severe combined immunodeficiency: Baseline features of the first fifty patients of the primary immune deficiency treatment consortium prospective study 6901

Christopher C. Dvorak*, Morton J. Cowan, Brent R. Logan, Luigi D. Notarangelo, Linda M. Griffith, Jennifer M. Puck, Donald B. Kohn, William T. Shearer, Richard J. O'Reilly, Thomas A. Fleisher, Sung Yun Pai, I. Celine Hanson, Michael A. Pulsipher, Ramsay L Fuleihan, Alexandra Filipovich, Frederick Goldman, Neena Kapoor, Trudy Small, Angela Smith, Ka Wah ChanGeoff Cuvelier, Jennifer Heimall, Alan Knutsen, Brett Loechelt, Theodore Moore, Rebecca H. Buckley

*Corresponding author for this work

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

The Primary Immune Deficiency Treatment Consortium (PIDTC) consists of 33 centers in North America. We hypothesized that the analysis of uniform data on patients with severe combined immunodeficiency (SCID) enrolled in a prospective protocol will identify variables that contribute to optimal outcomes following treatment. We report baseline clinical, immunologic, and genetic features of the first 50 patients enrolled, and the initial therapies administered, reflecting current practice in the diagnosis and treatment of both typical (n = 37) and atypical forms (n = 13) of SCID. From August 2010 to May 2012, patients with suspected SCID underwent evaluation and therapy per local center practices. Diagnostic information was reviewed by the PIDTC eligibility review panel, and hematopoietic cell transplantation (HCT) details were obtained from the Center for International Blood and Marrow Transplant Research. Most patients (92 %) had mutations in a known SCID gene. Half of the patients were diagnosed by newborn screening or family history, were younger than those diagnosed by clinical signs (median 15 vs. 181 days; P = <0.0001), and went to HCT at a median of 67 days vs. 214 days of life (P = <0.0001). Most patients (92 %) were treated with HCT within 1-2 months of diagnosis. Three patients were treated with gene therapy and 1 with enzyme replacement. The PIDTC plans to enroll over 250 such patients and analyze short and long-term outcomes for factors beneficial or deleterious to survival, clinical outcome, and T- and B-cell reconstitution, and which biomarkers are predictive of these outcomes.

Original languageEnglish (US)
Pages (from-to)1156-1164
Number of pages9
JournalJournal of Clinical Immunology
Volume33
Issue number7
DOIs
StatePublished - Jul 2 2013

Fingerprint

Severe Combined Immunodeficiency
Natural History
Prospective Studies
Cell Transplantation
Therapeutics
North America
Genetic Therapy
B-Lymphocytes
Biomarkers
Bone Marrow
Newborn Infant
Transplants
Mutation
Survival
Enzymes

Keywords

  • Severe combined immunodeficiency
  • hematopoietic cell transplantation
  • newborn screening

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Dvorak, Christopher C. ; Cowan, Morton J. ; Logan, Brent R. ; Notarangelo, Luigi D. ; Griffith, Linda M. ; Puck, Jennifer M. ; Kohn, Donald B. ; Shearer, William T. ; O'Reilly, Richard J. ; Fleisher, Thomas A. ; Pai, Sung Yun ; Hanson, I. Celine ; Pulsipher, Michael A. ; Fuleihan, Ramsay L ; Filipovich, Alexandra ; Goldman, Frederick ; Kapoor, Neena ; Small, Trudy ; Smith, Angela ; Chan, Ka Wah ; Cuvelier, Geoff ; Heimall, Jennifer ; Knutsen, Alan ; Loechelt, Brett ; Moore, Theodore ; Buckley, Rebecca H. / The natural history of children with severe combined immunodeficiency : Baseline features of the first fifty patients of the primary immune deficiency treatment consortium prospective study 6901. In: Journal of Clinical Immunology. 2013 ; Vol. 33, No. 7. pp. 1156-1164.
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abstract = "The Primary Immune Deficiency Treatment Consortium (PIDTC) consists of 33 centers in North America. We hypothesized that the analysis of uniform data on patients with severe combined immunodeficiency (SCID) enrolled in a prospective protocol will identify variables that contribute to optimal outcomes following treatment. We report baseline clinical, immunologic, and genetic features of the first 50 patients enrolled, and the initial therapies administered, reflecting current practice in the diagnosis and treatment of both typical (n = 37) and atypical forms (n = 13) of SCID. From August 2010 to May 2012, patients with suspected SCID underwent evaluation and therapy per local center practices. Diagnostic information was reviewed by the PIDTC eligibility review panel, and hematopoietic cell transplantation (HCT) details were obtained from the Center for International Blood and Marrow Transplant Research. Most patients (92 {\%}) had mutations in a known SCID gene. Half of the patients were diagnosed by newborn screening or family history, were younger than those diagnosed by clinical signs (median 15 vs. 181 days; P = <0.0001), and went to HCT at a median of 67 days vs. 214 days of life (P = <0.0001). Most patients (92 {\%}) were treated with HCT within 1-2 months of diagnosis. Three patients were treated with gene therapy and 1 with enzyme replacement. The PIDTC plans to enroll over 250 such patients and analyze short and long-term outcomes for factors beneficial or deleterious to survival, clinical outcome, and T- and B-cell reconstitution, and which biomarkers are predictive of these outcomes.",
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Dvorak, CC, Cowan, MJ, Logan, BR, Notarangelo, LD, Griffith, LM, Puck, JM, Kohn, DB, Shearer, WT, O'Reilly, RJ, Fleisher, TA, Pai, SY, Hanson, IC, Pulsipher, MA, Fuleihan, RL, Filipovich, A, Goldman, F, Kapoor, N, Small, T, Smith, A, Chan, KW, Cuvelier, G, Heimall, J, Knutsen, A, Loechelt, B, Moore, T & Buckley, RH 2013, 'The natural history of children with severe combined immunodeficiency: Baseline features of the first fifty patients of the primary immune deficiency treatment consortium prospective study 6901', Journal of Clinical Immunology, vol. 33, no. 7, pp. 1156-1164. https://doi.org/10.1007/s10875-013-9917-y

The natural history of children with severe combined immunodeficiency : Baseline features of the first fifty patients of the primary immune deficiency treatment consortium prospective study 6901. / Dvorak, Christopher C.; Cowan, Morton J.; Logan, Brent R.; Notarangelo, Luigi D.; Griffith, Linda M.; Puck, Jennifer M.; Kohn, Donald B.; Shearer, William T.; O'Reilly, Richard J.; Fleisher, Thomas A.; Pai, Sung Yun; Hanson, I. Celine; Pulsipher, Michael A.; Fuleihan, Ramsay L; Filipovich, Alexandra; Goldman, Frederick; Kapoor, Neena; Small, Trudy; Smith, Angela; Chan, Ka Wah; Cuvelier, Geoff; Heimall, Jennifer; Knutsen, Alan; Loechelt, Brett; Moore, Theodore; Buckley, Rebecca H.

In: Journal of Clinical Immunology, Vol. 33, No. 7, 02.07.2013, p. 1156-1164.

Research output: Contribution to journalArticle

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T1 - The natural history of children with severe combined immunodeficiency

T2 - Baseline features of the first fifty patients of the primary immune deficiency treatment consortium prospective study 6901

AU - Dvorak, Christopher C.

AU - Cowan, Morton J.

AU - Logan, Brent R.

AU - Notarangelo, Luigi D.

AU - Griffith, Linda M.

AU - Puck, Jennifer M.

AU - Kohn, Donald B.

AU - Shearer, William T.

AU - O'Reilly, Richard J.

AU - Fleisher, Thomas A.

AU - Pai, Sung Yun

AU - Hanson, I. Celine

AU - Pulsipher, Michael A.

AU - Fuleihan, Ramsay L

AU - Filipovich, Alexandra

AU - Goldman, Frederick

AU - Kapoor, Neena

AU - Small, Trudy

AU - Smith, Angela

AU - Chan, Ka Wah

AU - Cuvelier, Geoff

AU - Heimall, Jennifer

AU - Knutsen, Alan

AU - Loechelt, Brett

AU - Moore, Theodore

AU - Buckley, Rebecca H.

PY - 2013/7/2

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N2 - The Primary Immune Deficiency Treatment Consortium (PIDTC) consists of 33 centers in North America. We hypothesized that the analysis of uniform data on patients with severe combined immunodeficiency (SCID) enrolled in a prospective protocol will identify variables that contribute to optimal outcomes following treatment. We report baseline clinical, immunologic, and genetic features of the first 50 patients enrolled, and the initial therapies administered, reflecting current practice in the diagnosis and treatment of both typical (n = 37) and atypical forms (n = 13) of SCID. From August 2010 to May 2012, patients with suspected SCID underwent evaluation and therapy per local center practices. Diagnostic information was reviewed by the PIDTC eligibility review panel, and hematopoietic cell transplantation (HCT) details were obtained from the Center for International Blood and Marrow Transplant Research. Most patients (92 %) had mutations in a known SCID gene. Half of the patients were diagnosed by newborn screening or family history, were younger than those diagnosed by clinical signs (median 15 vs. 181 days; P = <0.0001), and went to HCT at a median of 67 days vs. 214 days of life (P = <0.0001). Most patients (92 %) were treated with HCT within 1-2 months of diagnosis. Three patients were treated with gene therapy and 1 with enzyme replacement. The PIDTC plans to enroll over 250 such patients and analyze short and long-term outcomes for factors beneficial or deleterious to survival, clinical outcome, and T- and B-cell reconstitution, and which biomarkers are predictive of these outcomes.

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KW - Severe combined immunodeficiency

KW - hematopoietic cell transplantation

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