People with Primary Immune Deficiency (PID) may develop severe, life-threatening infections
as a result of inherited defects in the genes that normally instruct blood-forming cells to
develop and to fight infections. PID diseases include Severe Combined Immune Deficiency
(SCID), leaky SCID, Omenn syndrome (OS), and Reticular Dysgenesis (RD). PIDs may be treated
by transplantation of bone marrow stem cells from a healthy person or, in some cases, by
enzyme replacement or by gene therapy. Patients with SCID were among the first to receive
bone marrow stem cell (also called hematopoietic cells) transplantation (HCT) more than 40
years ago, and HCT is the standard treatment today for this group of diseases. Since PID
diseases are rare, there are not enough patients at any single center to determine the full
range of causes, natural history, or best methods of treatment. For this research study many
PID centers across North America have organized into the Primary Immune Deficiency Treatment
Consortium (PIDTC) to pool their experience and study PIDs together. Researchers will
collect information on your general health, psychological and developmental health, and the
current status of your immune system to help better define future approaches to PID
treatments.
Investigators from institutions participating in this consortium will submit data to the
PIDTC Review Panel to determine eligibility and stratum assignment. The eligibility of the
patients and their stratification by SCID variant and treatment employed for SCID will be
as follows.
Inclusion Criteria:
Strata A, B, and C (Part 1 - Retrospective Study).
Patients eligible for the retrospective analysis include all patients diagnosed to have
SCID who were treated at the institutions participating in this consortium from 1968 until
December 31, 2010, who are not already enrolled on PIDTC Protocol 1. Subjects who received
HCT/GT/ERT prior to December 31, 2010 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. Patients who meet the following inclusion criteria and who
received HCT are eligible for enrollment into Stratum A (Classic SCID) of the study:
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 T cells of maternal origin present, but with < 10% of normal T
cell function (as measured by response to PHA).
Stratum B, Leaky SCID, Omenn Syndrome, Reticular Dysgenesis. Patients who meet the
following criteria are eligible for enrollment into Stratum B of the study: Leaky SCID
- Reduced number of CD3 T cells - for age up to 2 years ≥ 300 and < 1000/microliter;
for > 2 years up to 4 years ≥ 300 and < 800/microliter ; for > 4 years ≥ 300 and <
600/microliter
- Absence of maternal engraftment ≥ 10% and ≤ 30% of lower limit of normal T cell
function (as measured by response to PHA)
Omenn Syndrome (OS)
- Generalized skin rash
- Absence of maternal engraftment
- Detectable CD3 T cells, ≥ 300/microliter
- Absent or low (up to 30% of normal) T cell proliferation to antigens to which the
patient has been exposed
- If the proliferation to antigen was not performed, but at least 4 of the following 9
supportive criteria, at least one of which must be among those marked with an
asterisk (*) are present, the patient is eligible: Hepatomegaly; Splenomegaly;
Lymphadenopathy; Elevated IgE; Elevated absolute eosinophil count; *Oligoclonal T
cells measured by CDR3 length or flow cytometry >80% of CD4+ T cells are CD45RO+ ;
*Proliferation to PHA is reduced <30% of lower limit of normal or SI <20;
*Proliferative response in mixed leukocyte reaction is reduced <30% of lower limit of
normal or SI <5
Reticular Dysgenesis (RD)
- Absence or very low number of T cells (CD3 T cells <300/microliter)
- No or very low (<10% of lower limit of normal) T cell function (as measured by
response to phytohemagglutinin (PHA)
- Severe congenital neutropenia (absolute neutrophil count <200/microliter)
- Sensorineural deafness and/or absence of granulopoiesis at bone marrow examination
Stratum C, SCID with Non-HCT Treatments. Patients who meet the following criteria and were
treated with PEG-ADA or gene therapy with autologous modified cells are eligible for
enrollment into Stratum C (SCID with non-HCT treatments) of the study.
- ADA Deficient SCID treated with PEG-ADA
- Any SCID treated with gene therapy
Strata A, B, and C (Part 2 - Cross-Sectional Study)
Patient inclusion criteria for the cross sectional study: Eligibility for Strata A, B and
C are the same as for the retrospective study except that all the patients in the
cross-sectional study are currently surviving and are at least 2 years post the most
recent class of therapy.
Exclusion Criteria:
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
- Most patients with other PIDs such as nucleoside phosphorylase deficiency, ZAP70
deficiency, CD40 ligand deficiency, NEMO deficiency, XLP, cartilage hair hypoplasia
or ataxia telangiectasia will not meet the inclusion criteria for Stratum A, B, or C
above. However, a patient with one of the above may meet the inclusion criteria for
Stratum B and if so will be included.
- 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
University of Alabama at Birmingham, Birmingham, Alabama 35233, United States; Recruiting
Fredrick Goldman, MD, Phone: 205-939-5855, Email: fgoldman@peds.uab.edu
Fredrick Goldman, MD, Principal Investigator
British Columbia Children's Hospital, Vancouver, British Columbia V6H 3V4, Canada; Recruiting
Jeffrey Davis, MD, Phone: (604) 875-3577, Email: jdavis@cw.bc.ca
Jeffrey Davis, MD, Principal Investigator
Children's Hospital Los Angeles, Los Angeles, California 90027, United States; Recruiting
Renna Killen, RN, Phone: 323-361-2217, Email: rkillen@chla.usc.edu
Neena Kapoor, MD, Principal Investigator
University of California, Los Angeles, Los Angeles, California 90095-1752, United States; Recruiting
Theodore Moore, MD, Phone: 310-825-6708, Email: TBMoore@mednet.ucla.edu
Theodore Moore, MD, Principal Investigator
University of California San Francisco Children's Hospital, San Francisco, California 94143-1278, United States; Recruiting
Elizabeth Dunn, Phone: 415-476-4860, Email: DunnE@peds.ucsf.edu
Morton Cowan, MD, Principal Investigator
Stanford University, Stanford, California 94305, United States; Recruiting
Matthew Porteus, MD, Phone: 650-725-6520, Email: mporteus@stanford.edu
Matthew Porteus, MD, Principal Investigator
Children's Hospital Denver, Denver, Colorado 80220, United States; Not yet recruiting
Ralph Quinones, MD, Phone: 720-777-6511, Email: RQuinones@tchden.org
Ralph Quinones, MD, Principal Investigator
Children's National Medical Center, Washington, District of Columbia 20010-2970, United States; Recruiting
Brett Loechelt, MD, Phone: 202-476-2800, Email: BLoechel@cnmc.org
Brett Loechelt, MD, Principal Investigator
Children's Healthcare of Atlanta/Emory University School of Medicine, Atlanta, Georgia 30322, United States; Recruiting
Ann Haight, MD, Phone: 404-785-1272, Email: Ann.haight@choa.org
Ann Haight, MD, Principal Investigator
Children's Memorial Hospital, Chicago, Illinois 60614, United States; Recruiting
Meredith Marshall, Phone: 773-880-3459, Email: memarshall@childrensmemorial.org
Ramsay Fukeihan, MD, Principal Investigator
Children's Hospital/LSUHC, New Orleans, Louisiana 70118, United States; Not yet recruiting
Lolie Yu, MD, Phone: 504-896-9740, Email: lyu@lsuhsc.edu
Lolie Yu, MD, Principal Investigator
Cancer Care Manitoba, Winnipeg, Manitoba R3E 0V9, Canada; Not yet recruiting
Marlis Schroeder, MD, Phone: (204) 787-4372, Email: marlis.schroeder@cancercare.mb.ca
Marlis Schroeder, MD, Principal Investigator
NIH Clinical Center Genetic Immunotherapy Section, Bethesda, Maryland 20892, United States; Not yet recruiting
Elizabeth Kang, MD, Phone: 301-402-7567, Email: ekang@niaid.nih.gov
Elizabeth Kang, MD, Principal Investigator
Children's Hospital Boston, Boston, Massachusetts 02115, United States; Recruiting
Jennifer Braunstein, PNP, Phone: 617-355-2457, Email: jennifer.braunstein@childrens.harvard.edu
Sung-Yun Pai, MD, Principal Investigator
University of Michigan Health System, Ann Arbor, Michigan 48109, United States; Recruiting
James Connelly, MD, Phone: 737-936-4000, Email: jaconnel@med.umich.edu
James Connelly, MD, Principal Investigator
University of Minnesota Medical Center, Minneapolis, Minnesota 55455, United States; Recruiting
Angie Smith, MD, Phone: 612-626-2778, Email: smith719@umn.edu
Angie Smith, MD, Principal Investigator
Cardinal Glennon Children's Medical Center, St. Louis, Missouri 63104, United States; Recruiting
Wendy Sanders, RN, Phone: 314-268-2700, Ext: 3513, Email: Wendy_Sanders@ssmhc.com
Alan Knutsen, MD, Principal Investigator
Washington University St Louis Children's Hospital, St. Louis, Missouri 63110, United States; Not yet recruiting
Shalini Shenoy, MD, Phone: 314-454-6018, Email: shenoy@wustl.edu
Shalini Shenoy, MD, Principal Investigator
Hackensack University Medical Center, Hackensack, New Jersey 07601, United States; Recruiting
Alfred Gillio, MD, Phone: 201-996-5645, Email: agillio@humed.com
Alfred Gillio, MD, Principal Investigator
Memorial Sloan-Kettering Cancer Center, New York, New York 10065, United States; Recruiting
Carolyn Doorish, Phone: 646-888-5718, Email: doorishc@mskc.org
Richard J O'Reilly, MD, Principal Investigator
Duke University, Durham, North Carolina 27710, United States; Recruiting
Rebecca Buckley, MD, Phone: 919-684-2922, Email: buck1003@mc.duke.edu
Rebecca Buckley, MD, Principal Investigator
Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, United States; Recruiting
Angie Poston, BS, Phone: 513-636-8815, Email: angela.poston@cchmc.org
Lisa Filipovich, MD, Principal Investigator
Oregon Health and Science University, Portland, Oregon 97239-3098, United States; Not yet recruiting
Evan Shereck, MD, Phone: 503-494-0829, Email: Shereck@ohsu.edu
Evan Shereck, MD, Principal Investigator
The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States; Recruiting
Kathleen Sullivan, MD, PhD, Phone: 215-590-1697, Email: sullivak@mail.med.upenn.edu
Kathleen Sullivan, MD, PhD, Principal Investigator
CHU St. Justine, Montreal, Quebec H3T 1C5, Canada; Not yet recruiting
Elie Haddad, MD, Phone: (514) 345-4931, Ext: 6217, Email: elie.haddad@umontreal.ca
Elie Haddad, MD, Principal Investigator
University of Texas Southwestern Medical Center/Children's of Dallas, Dallas, Texas 75390-9263, United States; Recruiting
Victor Aquino, MD, Phone: 214-648-8800, Email: victor.aquino@utsouthwestern.edu
Victor Aquino, MD, Principal Investigator
Texas Children's Hospital, Houston, Texas 77030-2399, United States; Recruiting
Chivon McMullen-Jackson, RN, BSN, Phone: 832-824-1339, Email: cdmcmull@texaschildrens.org
William Shearer, MD, Principal Investigator
Methodist Children's Hospital of South Texas/Texas Transplant Institute, San Antonio, Texas 78229, United States; Recruiting
Ka Wah Chan, MD, Phone: 210-575-7268, Email: Kawah.Chan@MHShealth.com
Ka Wah Chan, MD, Principal Investigator
Primary Children's Medical Center/University of Utah, Salt Lake City, Utah 84113, United States; Recruiting
Michael Pulsipher, MD, Phone: 801-662-4830, Email: michael.pulsipher@hsc.utah.edu
Michael Pulsipher, MD, Principal Investigator
University of Washington & Seattle Children's Hospital/ Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, United States; Recruiting
Lauri M. Burroughs, MD, Phone: 206-667-2396, Email: lburroug@fhcrc.org
Lauri Burroughs, MD, Principal Investigator
Medical College of Wisconsin, Milwaukee, Wisconsin 53226-4874, United States; Recruiting
John M. Routes, MD, Phone: 414-456-4802, Email: jroutes@mce.edu
James Casper, MD, Phone: (414) 456-4170, Email: jcasper@mcw.edu
John M. Routes, MD, Principal Investigator
