Patients Treated for SCID (1968-Present)

NCT01346150 | Unknown

• 1 other identifier: DAIT RDCRN PIDTC-6902
• Study Type: observational
• Target: 1,007
• Locations: 2 countries
• Sites: 36

Brief Summary

Individuals with a past diagnosis of severe combined immune deficiency (including many cases of "leaky SCID", Omenn syndrome, and reticular dysgenesis) who have undergone blood and marrow transplant, gene therapy, or enzyme replacement in the past may be eligible for this study. The purpose of study is to look backwards at what has already been done in the. Over 800 patients with SCID are expected to be enrolled, making this one of the largest studies ever to describe outcomes for patients with SCID treated at many different hospitals around North America.

Conditions

SCID; ADA-SCID; XSCID; Leaky SCID; Omenn Syndrome; Reticular Dysgenesis

Outcome Measures

Primary Outcomes (2)

• Retrospective Study - Part 1

  Overall survival

  1, 5, 10, 20, >20 years

• Cross-Sectional Study - Part 2

  Full immune reconstitution

  2 to > 20 years

Secondary Outcomes (4)

• Retrospective Study Part 1

  1 year to > 20 years

• Retrospective Study - Part 1

  3 months to >20 years

• Cross-Sectional Study - Part 2

  2 to >20 years

• Cross-Sectional Study - Part 2

  2 to >20 years

Study Arms (3)

Stratum A -Typical SCID

Typical Severe Combined Immunodeficiency (SCID), Adenosine Deaminase-Deficient ADA SCID, and X-linked SCID (XSCID) who received a transplant

Stratum B - Atypical SCID

Leaky SCID, Omenn Syndrome, and Reticular Dysgenesis who received a transplant

Stratum C - SCID w/Non-HCT Treatments

SCID who received Polyethylene Glycol -Adenosine Deaminase Enzyme Replacement Therapy (PEG-ADA ERT) or gene therapy

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals with diagnosis of SCID or SCID variants treated at Participating Consortium Centers from 1968-Present

You may qualify if:

• Strata A, B, and C (Part 1 - Retrospective Study)-
• Individuals with Severe Combined Immune Deficiency (SCID) diagnosis who:
• were treated at a location participating in this consortium from 1968 until present, and
• are not enrolled in RDCRN PIDTC-6901 (ClinicalTrials.gov ID: NCT01186913).
• Subjects who received HCT/GT/ERT prior to the present date are eligible for the retrospective study. The enrollment criteria for subjects who died prior to definitive therapy are the same as for Strata A, B and C.
• Stratum A, Typical SCID:
• Absence or very low number of T cells (CD3 T cells \< 300/microliter), and no or very low T cell function (\< 10% of lower limit of normal) as measured by response to phytohemagglutinin (PHA) or cells of maternal origin present.
• If maternal cells are present but the patient does not meet criteria for very low T cell function as defined, the assigned reviewers for the potential subject, and if necessary, the full PID-SCID RP will review the laboratory report to determine if criteria of maternal engraftment are met for Protocol 6902.
• Laboratory report of testing for maternal engraftment is required, for evaluation by the PID-SCID RP.
• Stratum B, Leaky SCID, Omenn Syndrome, Reticular Dysgenesis:
• Individuals who meet the following criteria are eligible for enrollment into Stratum B of the study:
• Leaky SCID-
• Maternal lymphocytes tested for and not detected and,
• Either one or both of the following (a,b):
• a) \< 50% of lower limit of normal T cell function (as measured by response to PHA OR \< 50% of lower limit of normal T cell function as measured by response to CD3/CD28 antibody, b) Absent or \< 30% lower limit of normal proliferative responses to candida and tetanus toxoid antigens postvaccination or exposure,

You may not qualify if:

• Parts 1 and 2 - Retrospective and Cross-Sectional Studies -
• Lack of appropriate testing to rule out HIV infection after 1997 (p24 antigen or more sensitive) or other cause of secondary immunodeficiency,
• Presence of DiGeorge syndrome,
• MHC Class I and MHC Class II antigen deficiency are excluded,
• Metabolic conditions that imitate SCID or related disorders such as folate transporter deficiency, severe zinc deficiency, transcobalamin deficiency.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Primary Immune Deficiency Treatment Consortium (PIDTC): collaborator
• National Center for Advancing Translational Sciences (NCATS): collaborator

Study Sites (36)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Mattel Children's Hospital UCLA: Division of Pediatric Hematology/Oncology

Los Angeles, California, 90095-1752, United States

Location

Lucile Salter Packard Children's Hospital at Stanford

Palo Alto, California, 94305, United States

Location

University of California San Francisco Children's Hospital

San Francisco, California, 94143-1278, United States

Location

Children's Hospital Denver:Center for Cancer and Blood Disorders

Denver, Colorado, 80220, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010-2970, United States

Location

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

Children's Healthcare of Atlanta/Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

Lurie Children's Hospital of Chicago

Chicago, Illinois, 60614, United States

Location

Children's Hospital/Louisiana State University Health Sciences Center

New Orleans, Louisiana, 70118, United States

Location

NIH Clinical Center Genetic Immunotherapy Section

Bethesda, Maryland, 20892, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota Medical Center

Minneapolis, Minnesota, 55455, United States

Location

SSM Cardinal Glennon Children's Medical Center

St Louis, Missouri, 63104, United States

Location

Washington University St Louis Children's Hospital

St Louis, Missouri, 63110, United States

Location

Hackensack University Medical Center: Department of Pediatrics

Hackensack, New Jersey, 07601, United States

Location

Memorial Sloan-Kettering Cancer Center: Department of Pediatrics

New York, New York, 10065, United States

Location

Duke University Medical Center: Department of Pediatrics, Division of Allergy/Immunology

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Oregon Health & Science University: Pediatric Hematology/Oncology

Portland, Oregon, 97239-3098, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

University of Texas Southwestern Medical Center Dallas

Dallas, Texas, 75235, United States

Location

Texas Children's Hospital

Houston, Texas, 77030-2399, United States

Location

Methodist Children's Hospital of South Texas

San Antonio, Texas, 78229, United States

Location

Primary Children's Medical Center/University of Utah

Salt Lake City, Utah, 84113, United States

Location

Fred Hutchinson Cancer Research Center: Clinical Research Division and Pediatric Stem Cell Transplantation Center

Seattle, Washington, 98101, United States

Location

University of Wisconsin/ American Family Children's Hospital

Madison, Wisconsin, 53705-2275, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226-4874, United States

Location

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

British Columbia Children's Hospital

Vancouver, British Columbia, V6H 3V4, Canada

Location

Cancer Care Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

The Hospital for Sick Children (SickKids)

Toronto, Ontario, M5G 1XB, Canada

Location

CHU St. Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Related Publications (14)

• Griffith LM, Cowan MJ, Kohn DB, Notarangelo LD, Puck JM, Schultz KR, Buckley RH, Eapen M, Kamani NR, O'Reilly RJ, Parkman R, Roifman CM, Sullivan KE, Filipovich AH, Fleisher TA, Shearer WT. Allogeneic hematopoietic cell transplantation for primary immune deficiency diseases: current status and critical needs. J Allergy Clin Immunol. 2008 Dec;122(6):1087-96. doi: 10.1016/j.jaci.2008.09.045. Epub 2008 Nov 6.

  PMID: 18992926 BACKGROUND

• Pai SY, Logan BR, Griffith LM, Buckley RH, Parrott RE, Dvorak CC, Kapoor N, Hanson IC, Filipovich AH, Jyonouchi S, Sullivan KE, Small TN, Burroughs L, Skoda-Smith S, Haight AE, Grizzle A, Pulsipher MA, Chan KW, Fuleihan RL, Haddad E, Loechelt B, Aquino VM, Gillio A, Davis J, Knutsen A, Smith AR, Moore TB, Schroeder ML, Goldman FD, Connelly JA, Porteus MH, Xiang Q, Shearer WT, Fleisher TA, Kohn DB, Puck JM, Notarangelo LD, Cowan MJ, O'Reilly RJ. Transplantation outcomes for severe combined immunodeficiency, 2000-2009. N Engl J Med. 2014 Jul 31;371(5):434-46. doi: 10.1056/NEJMoa1401177.

  PMID: 25075835 RESULT

• Shearer WT, Dunn E, Notarangelo LD, Dvorak CC, Puck JM, Logan BR, Griffith LM, Kohn DB, O'Reilly RJ, Fleisher TA, Pai SY, Martinez CA, Buckley RH, Cowan MJ. Establishing diagnostic criteria for severe combined immunodeficiency disease (SCID), leaky SCID, and Omenn syndrome: the Primary Immune Deficiency Treatment Consortium experience. J Allergy Clin Immunol. 2014 Apr;133(4):1092-8. doi: 10.1016/j.jaci.2013.09.044. Epub 2013 Nov 28.

  PMID: 24290292 RESULT

• Haddad E, Allakhverdi Z, Griffith LM, Cowan MJ, Notarangelo LD. Survey on retransplantation criteria for patients with severe combined immunodeficiency. J Allergy Clin Immunol. 2014 Feb;133(2):597-9. doi: 10.1016/j.jaci.2013.10.022. Epub 2013 Dec 10. No abstract available.

  PMID: 24331379 RESULT

• Griffith LM, Cowan MJ, Notarangelo LD, Kohn DB, Puck JM, Shearer WT, Burroughs LM, Torgerson TR, Decaluwe H, Haddad E; workshop participants. Primary Immune Deficiency Treatment Consortium (PIDTC) update. J Allergy Clin Immunol. 2016 Aug;138(2):375-85. doi: 10.1016/j.jaci.2016.01.051. Epub 2016 Apr 22.

  PMID: 27262745 RESULT

• Griffith LM, Cowan MJ, Notarangelo LD, Kohn DB, Puck JM, Pai SY, Ballard B, Bauer SC, Bleesing JJ, Boyle M, Brower A, Buckley RH, van der Burg M, Burroughs LM, Candotti F, Cant AJ, Chatila T, Cunningham-Rundles C, Dinauer MC, Dvorak CC, Filipovich AH, Fleisher TA, Bobby Gaspar H, Gungor T, Haddad E, Hovermale E, Huang F, Hurley A, Hurley M, Iyengar S, Kang EM, Logan BR, Long-Boyle JR, Malech HL, McGhee SA, Modell F, Modell V, Ochs HD, O'Reilly RJ, Parkman R, Rawlings DJ, Routes JM, Shearer WT, Small TN, Smith H, Sullivan KE, Szabolcs P, Thrasher A, Torgerson TR, Veys P, Weinberg K, Zuniga-Pflucker JC; workshop participants. Primary Immune Deficiency Treatment Consortium (PIDTC) report. J Allergy Clin Immunol. 2014 Feb;133(2):335-47. doi: 10.1016/j.jaci.2013.07.052. Epub 2013 Oct 15.

  PMID: 24139498 RESULT

• 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 R, Filipovich A, Goldman F, Kapoor N, Small T, Smith A, Chan KW, Cuvelier G, Heimall J, Knutsen A, Loechelt B, Moore T, Buckley RH. 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. J Clin Immunol. 2013 Oct;33(7):1156-64. doi: 10.1007/s10875-013-9917-y. Epub 2013 Jul 2.

  PMID: 23818196 RESULT

• Griffith LM, Cowan MJ, Notarangelo LD, Puck JM, Buckley RH, Candotti F, Conley ME, Fleisher TA, Gaspar HB, Kohn DB, Ochs HD, O'Reilly RJ, Rizzo JD, Roifman CM, Small TN, Shearer WT; Workshop Participants. Improving cellular therapy for primary immune deficiency diseases: recognition, diagnosis, and management. J Allergy Clin Immunol. 2009 Dec;124(6):1152-60.e12. doi: 10.1016/j.jaci.2009.10.022.

  PMID: 20004776 RESULT

• Kohn DB, Hershfield MS, Puck JM, Aiuti A, Blincoe A, Gaspar HB, Notarangelo LD, Grunebaum E. Consensus approach for the management of severe combined immune deficiency caused by adenosine deaminase deficiency. J Allergy Clin Immunol. 2019 Mar;143(3):852-863. doi: 10.1016/j.jaci.2018.08.024. Epub 2018 Sep 5.

  PMID: 30194989 RESULT

• Miggelbrink AM, Logan BR, Buckley RH, Parrott RE, Dvorak CC, Kapoor N, Abdel-Azim H, Prockop SE, Shyr D, Decaluwe H, Hanson IC, Gillio A, Davila Saldana BJ, Eibel H, Hopkins G, Walter JE, Whangbo JS, Kohn DB, Puck JM, Cowan MJ, Griffith LM, Haddad E, O'Reilly RJ, Notarangelo LD, Pai SY. B-cell differentiation and IL-21 response in IL2RG/JAK3 SCID patients after hematopoietic stem cell transplantation. Blood. 2018 Jun 28;131(26):2967-2977. doi: 10.1182/blood-2017-10-809822. Epub 2018 May 4.

  PMID: 29728406 RESULT

• Haddad E, Logan BR, Griffith LM, Buckley RH, Parrott RE, Prockop SE, Small TN, Chaisson J, Dvorak CC, Murnane M, Kapoor N, Abdel-Azim H, Hanson IC, Martinez C, Bleesing JJH, Chandra S, Smith AR, Cavanaugh ME, Jyonouchi S, Sullivan KE, Burroughs L, Skoda-Smith S, Haight AE, Tumlin AG, Quigg TC, Taylor C, Davila Saldana BJ, Keller MD, Seroogy CM, Desantes KB, Petrovic A, Leiding JW, Shyr DC, Decaluwe H, Teira P, Gillio AP, Knutsen AP, Moore TB, Kletzel M, Craddock JA, Aquino V, Davis JH, Yu LC, Cuvelier GDE, Bednarski JJ, Goldman FD, Kang EM, Shereck E, Porteus MH, Connelly JA, Fleisher TA, Malech HL, Shearer WT, Szabolcs P, Thakar MS, Vander Lugt MT, Heimall J, Yin Z, Pulsipher MA, Pai SY, Kohn DB, Puck JM, Cowan MJ, O'Reilly RJ, Notarangelo LD. SCID genotype and 6-month posttransplant CD4 count predict survival and immune recovery. Blood. 2018 Oct 25;132(17):1737-1749. doi: 10.1182/blood-2018-03-840702. Epub 2018 Aug 28.

  PMID: 30154114 RESULT

• Dvorak CC, Haddad E, Buckley RH, Cowan MJ, Logan B, Griffith LM, Kohn DB, Pai SY, Notarangelo L, Shearer W, Prockop S, Kapoor N, Heimall J, Chaudhury S, Shyr D, Chandra S, Cuvelier G, Moore T, Shenoy S, Goldman F, Smith AR, Sunkersett G, Vander Lugt M, Caywood E, Quigg T, Torgerson T, Chandrakasan S, Craddock J, Davila Saldana BJ, Gillio A, Shereck E, Aquino V, DeSantes K, Knutsen A, Thakar M, Yu L, Puck JM. The genetic landscape of severe combined immunodeficiency in the United States and Canada in the current era (2010-2018). J Allergy Clin Immunol. 2019 Jan;143(1):405-407. doi: 10.1016/j.jaci.2018.08.027. Epub 2018 Sep 5.

  PMID: 30193840 RESULT

• Rayes A, Logan BR, Liu X, Dara J, Buckley RH, Oved JH, Kapoor N, Kapadia M, Chandra S, Martinez CA, Bunin N, Chandrakasan S, Chen K, Bednarski JJ, Haines HL, Eissa H, Talano JM, Keller MD, Ebens CL, Chaudhury S, Shereck EB, Aquino VM, Knutsen AP, Alexander JL, Gillio AP, Chellapandian D, Shah AJ, Miller HK, Vander Lugt MT, Seroogy CM, Dorsey MJ, Mousallem T, Parrott RE, O'Reilly RJ, Aguayo-Hiraldo PI, Prockop SE, Davila Saldana BJ, Thakar MS, Burroughs LM, Torgerson TR, Leiding JW, Marsh RA, Griffith LM, Pulsipher MA, Kohn DB, Notarangelo LD, Cowan MJ, Puck JM, Cuvelier GDE, Heimall J, Haddad E, Pai SY, Dvorak CC. Outcomes Following Matched Sibling Donor Transplantation for Severe Combined Immunodeficiency: A Report from the PIDTC. Blood Adv. 2025 Nov 25:bloodadvances.2025016812. doi: 10.1182/bloodadvances.2025016812. Online ahead of print.

  PMID: 41289158 DERIVED

• Cuvelier GDE, Logan BR, Prockop SE, Buckley RH, Kuo CY, Griffith LM, Liu X, Yip A, Hershfield MS, Ayoub PG, Moore TB, Dorsey MJ, O'Reilly RJ, Kapoor N, Pai SY, Kapadia M, Ebens CL, Forbes Satter LR, Burroughs LM, Petrovic A, Chellapandian D, Heimall J, Shyr DC, Rayes A, Bednarski JJ, Chandra S, Chandrakasan S, Gillio AP, Madden L, Quigg TC, Caywood EH, Davila Saldana BJ, DeSantes K, Eissa H, Goldman FD, Rozmus J, Shah AJ, Vander Lugt MT, Thakar MS, Parrott RE, Martinez C, Leiding JW, Torgerson TR, Pulsipher MA, Notarangelo LD, Cowan MJ, Dvorak CC, Haddad E, Puck JM, Kohn DB. Outcomes following treatment for ADA-deficient severe combined immunodeficiency: a report from the PIDTC. Blood. 2022 Aug 18;140(7):685-705. doi: 10.1182/blood.2022016196.

  PMID: 35671392 DERIVED

Related Links

• Primary Immune Deficiency Treatment Consortium (PIDTC)
• Division of Allergy, Immunology, and Transplantation (DAIT)
• National Institute of Allergy and Infectious Diseases (NIAID)
• National Center for Advancing Translational Sciences (NCATS)

Biospecimen

Retention: SAMPLES WITH DNA

Biospecimens may include blood, other tissues (e.g., buccal swab or brushing), and/or bone marrow.

MeSH Terms

Conditions

Severe combined immunodeficiency due to adenosine deaminase deficiency; X-Linked Combined Immunodeficiency Diseases; Severe Combined Immunodeficiency; Reticular dysgenesis

Condition Hierarchy (Ancestors)

Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Primary Immunodeficiency Diseases; Infant, Newborn, Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Elie Haddad, MD, PhD

  University of Montréal, CHU Sainte-Justine

  STUDY CHAIR

• Richard J. O'Reilly, MD

  Memorial Sloan Kettering Cancer Center

  STUDY CHAIR

• Morton J. Cowan, MD

  University of California, San Francisco

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2011
• First Posted: May 2, 2011
• Study Start: May 15, 2011
• Primary Completion: August 1, 2023
• Study Completion: August 1, 2023
• Last Updated: November 12, 2020

Record last verified: 2020-11

Locations

CA (5); US (31)