Patients Treated for Wiskott-Aldrich Syndrome (WAS) Since 1990

NCT02064933 | Completed

• 1 other identifier: DAIT RDCRN PIDTC-6904
• Study Type: observational
• Target: 305
• Locations: 2 countries
• Sites: 43

Brief Summary

Wiskott - Aldrich syndrome (WAS) is a rare serious medical condition that causes problems both with the immune system and with easy bruising and bleeding. The immune abnormalities cause patients with WAS to be very susceptible to infections. Depending on the specific type of primary immune deficiency diseases, there are effective treatments, including antibiotics, cellular therapy and gene therapy, but studies of large numbers of patients are needed to determine the full range of causes, natural history, or the best methods of treatment for long term success. This multicenter study combines retrospective, prospective and cross-sectional analyses of the transplant experiences for patients with WAS who have already received HCT since 1990, or who will undergo Hematopoietic cell transplant (HCT) during the study period. The retrospective and prospective portions of the study will address the impact of a number of pre and post-transplant factors on post-transplant disease correction and ultimate benefit from HCT and the cross-sectional portion of the study will assess the benefit of HCT 2 years post-HCT in consenting surviving patients.

Conditions

Wiskott-Aldrich Syndrome

Keywords

Wiskott-Aldrich Syndrome; Hematopoietic Stem Cell Transplantation; Genetic Therapy

Outcome Measures

Primary Outcomes (7)

• Longitudinal Analysis: Overall Survival From Time of HCT/Gene Therapy

  The event analyzed is death from any cause. The time to this event is the time from HCT/gene therapy to death or last follow-up.

  an expected average of 5 years

• Cross-Sectional Analysis: Proportion of Participants Achieving Full T Cell Reconstitution

  Full T cell reconstitution is defined by all of the following: * CD3 cell count within normal range for age. * CD4 cell count within normal range for age. * CD8 cell count within normal range for age * Donor T cell chimerism \> 95% * Lymphocyte proliferation to PHA. Proliferative responses to PHA within the normal range (at or above the lower limit of normal). When possible the proliferation to PHA should be calculated as a percentage of the lower limit of normal controls for that laboratory; alternatively, the lower limit of normal controls for the day may be used

  an expected average of 5 years

• Cross-Sectional Analysis: Proportion of Participants Achieving Full B Cell Reconstitution

  Full B cell reconstitution is defined by all of the following: * Quantitative immunoglobulins (IgG, IgM, and IgA) within normal range; each immunoglobulin level will be assessed separately. * Serologic confirmation of post immunization tetanus titer in protective range. * Serologic confirmation of post immunization pneumococcal titers in protective range (protective titers for \> 50% of the serotypes contained in the vaccine) following immunization

  an expected average of 5 years

• Cross-Sectional Analysis: Proportion of Participants Achieving Resolution of thrombocytopenia

  Resolution of thrombocytopenia defined by Platelets ≥ 150,000/microliter (transfusion independent for at least 7 consecutive days)

  an expected average of 5 years

• Cross-Sectional Analysis: Day of Recovery of Absolute Neutrophil Count (ANC) to 500 / uL

  Day of Recovery of Absolute Neutrophil Count (ANC) to 500 / uL is defined as the first day of at least 3 different days the ANC is measured as 500 / uL or greater

  an expected average of 5 years

• Cross-sectional Analysis: Day of Recovery of Platelet Count to 20,000 / uL

  Day of Recovery of Platelet Count to 20,000 / uL is defined as the first day of at least 3 laboratory values obtained on different days where the platelet count was measured as 20,000 / uL or greater, AND without platelet transfusions for at least 7 consecutive days immediately preceding this day.

  an expected average of 5 years

• Cross-sectional Analysis: Day of Recovery of Platelet Count to 50,000 / uL

  Day of Recovery of Platelet Count to 50,000 / uL is defined as the first day of at least 3 laboratory values obtained on different days where the platelet count was measured as 50,000 / uL or greater, AND without platelet transfusions for at least 7 consecutive days immediately preceding this day.

  an expected average of 5 years

Secondary Outcomes (24)

• Longitudinal Analysis: Proportion of Participants Achieving Hematologic Reconstitution

  an expected average of 5 years

• Longitudinal Analysis: Day of Recovery of Absolute Neutrophil Count (ANC) to 500 / uL

  an expected average of 5 years

• Longitudinal Analysis: Day of Recovery of Platelet Count to 20,000 / uL

  an expected average of 5 years

• Longitudinal Analysis: Day of Recovery of Platelet Count to 50,000 / uL

  an expected average of 5 years

• Longitudinal Analysis: Proportion of Participants Achieving Full T Cell Immune Reconstitution

  an expected average of 5 years

Study Arms (3)

Retrospective Cohort (Longitudinal Analysis)

Participants with WAS treated at consortium centers since 1990 who have received transplant (Stratum A) or gene therapy (Stratum B)

Prospective Cohort (Longitudinal Analysis)

Participants treated at consortium centers since 1990 who will receive transplant (Stratum A) or gene therapy (Stratum B)

Cross-Sectional Cohort (Cross-sectional Analysis)

Living participants with WAS who have received transplant (Stratum A) or gene therapy (Stratum B) at Consortium Centers 1990-Present And \>= 2 Years Post-Transplant

Eligibility Criteria

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

Study Population

Male WAS participants treated at consortium centers Since 1990

You may qualify if:

• WAS participants will be defined as males who have:
• thrombocytopenia (\< 100K) AND EITHER molecular diagnosis of WAS OR reduced WASP expression; OR
• thrombocytopenia (\< 100K) AND positive family history consistent with WAS diagnosis; OR
• chronic thrombocytopenia (\< 100K for minimum of 3 months) AND low mean platelet volume (MPV below normal range for age) AND EITHER recurrent and/or severe infections requiring treatment and/or eczema OR lack of antibody response to polysaccharide antigens or low IgM.
• Longitudinal Analysis (Retrospective and Prospective)
• Stratum A. Participants with WAS who have or will Receive HCT
• Participants with WAS who have received an HCT since January 1, 1990
• Stratum B. Participants with WAS who have or will Receive Gene Transfer
• Participants in which the intention is to treat with gene transfer with autologous modified cells
• Cross-Sectional Analysis (Strata A and B) 1. Participants with WAS who are surviving and at least 2 years after the most recent HCT or gene therapy.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Primary Immune Deficiency Treatment Consortium (PIDTC): collaborator
• Rare Diseases Clinical Research Network: collaborator

Study Sites (43)

Department of Pediatrics, University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California

Los Angeles, California, 90027, United States

Location

Department of Pediatrics, David Geffen School of Medicine at University of California, Los Angeles,

Los Angeles, California, 90095-1752, United States

Location

Lucile Salter Packard Children's Hospital at Stanford

Palo Alto, California, 94304, United States

Location

University of California, San Francisco Benioff Children's Hospital

San Francisco, California, 94143-1278, United States

Location

Children's Hospital Denver, University of Colorado

Denver, Colorado, 80220, United States

Location

Nemours Alfred I. duPont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

Children's National Hospital-George Washington University School of Medicine and Health Sciences

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

Location

Blood and Marrow Transplant Program, Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

Aflac Cancer and Blood Disorders Center, Emory/Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60614, United States

Location

Center for Cancer and Blood Disorders, Children's Hospital/Louisiana State University

New Orleans, Louisiana, 70118, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Department of Pediatrics, C. S. Mott Children's Hospital, University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Division of Pediatric Blood and Marrow Transplantation, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic Children's Center

Rochester, Minnesota, 55905, United States

Location

Cardinal Glennon Children's Hospital, Saint Louis University

St Louis, Missouri, 63104, United States

Location

Saint Louis Children's Hospital, Washington University

St Louis, Missouri, 63110, United States

Location

Institute for Pediatric Cancer and Blood Disorders, Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Department of Pediatrics, Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Department of Pediatrics, Golisano Children's Hospital, University of Rochester

Rochester, New York, 14642, United States

Location

Maria Fareri Children's Hospital, New York Medical College

Valhalla, New York, 10595, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital Medical Center, University of Cincinnati

Cincinnati, Ohio, 45229-3039, United States

Location

Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Division of Pediatric Hematology/Oncology, Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Children's Hospital of Philadelphia, University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Pediatrics, University of Texas Southwestern Medical Center

Dallas, Texas, 75390-9263, United States

Location

Baylor College of Medicine Section of Immunology, Allergy, and Retrovirology, Texas Children's Hospital

Houston, Texas, 77030-2399, United States

Location

Texas Transplant Institute, Methodist Children's Hospital

San Antonio, Texas, 78229, United States

Location

Primary Children's Hospital, University of Utah

Salt Lake City, Utah, 84113, United States

Location

Fred Hutchinson Cancer Research Center and University of Washington-Seattle Children's Hospital

Seattle, Washington, 98109, United States

Location

American Family Children's Hospital, University of Wisconsin

Madison, Wisconsin, 53705-2275, United States

Location

Children's Hospital of Wisconsin-Milwaukee

Milwaukee, Wisconsin, 53226, United States

Location

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

Children's & Women's Health Centre of British Columbia

Vancouver, British Columbia, V6H 3V4, Canada

Location

Cancer Care Manitoba, University of Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1XB, Canada

Location

CHU Sainte-Justine, Department of Pediatrics, University of Montreal

Montreal, Quebec, H3T 1C5, Canada

Location

Related Publications (10)

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• Burroughs LM, Petrovic A, Brazauskas R, Liu X, Griffith LM, Ochs HD, Bleesing JJ, Edwards S, Dvorak CC, Chaudhury S, Prockop SE, Quinones R, Goldman FD, Quigg TC, Chandrakasan S, Smith AR, Parikh S, Davila Saldana BJ, Thakar MS, Phelan R, Shenoy S, Forbes LR, Martinez C, Chellapandian D, Shereck E, Miller HK, Kapoor N, Barnum JL, Chong H, Shyr DC, Chen K, Abu-Arja R, Shah AJ, Weinacht KG, Moore TB, Joshi A, DeSantes KB, Gillio AP, Cuvelier GDE, Keller MD, Rozmus J, Torgerson T, Pulsipher MA, Haddad E, Sullivan KE, Logan BR, Kohn DB, Puck JM, Notarangelo LD, Pai SY, Rawlings DJ, Cowan MJ. Excellent outcomes following hematopoietic cell transplantation for Wiskott-Aldrich syndrome: a PIDTC report. Blood. 2020 Jun 4;135(23):2094-2105. doi: 10.1182/blood.2019002939.

  PMID: 32268350 RESULT

• Alexander JL, Davila Saldana BJ, Brazauskas R, Dammalapati SG, Griffith LM, Shah AJ, Shimano KA, Ochs HD, Bleesing J, Ebens CL, Kapadia M, Bauchat A, Kapoor N, Oved JH, Eissa H, Lust H, Keller MD, Haines H, Chandrakasan S, Talano JM, Rayes A, Madden LM, Shereck EB, Miller HK, Forbes Satter LR, Martinez CA, Rozmus J, Bednarski JJ, Yu LC, Chellapandian D, Aquino VM, Knutsen AP, Chong H, Chopek A, Gillio AP, Joshi A, Rangarajan HG, Moore TB, Andolina JR, DeSantes K, Vander Lugt MT, Prockop SE, Shyr D, Sullivan KE, Parikh SH, Weinacht KG, Torgerson TR, Marsh RA, Dvorak CC, Chan AY, Haddad E, Heimall J, Pulsipher MA, Leiding JW, Kohn DB, Puck JM, Notarangelo LD, Rawlings DJ, Cowan MJ, Petrovic A, Pai SY, Burroughs LM. Hematopoietic Cell Transplantation for Wiskott-Aldrich syndrome: A PIDTC Report. Blood Adv. 2025 Dec 4:bloodadvances.2025017662. doi: 10.1182/bloodadvances.2025017662. Online ahead of print.

  PMID: 41346295 DERIVED

Related Links

• Primary Immune Deficiency Treatment Consortium (PIDTC), Rare Clinical Diseases Research Network, National Institutes of Health
• Division of Allergy, Immunology, and Transplantation (DAIT)
• National Institute of Allergy and Infectious Diseases (NIAID)

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood and tissue samples

MeSH Terms

Conditions

Wiskott-Aldrich Syndrome

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphopenia; Leukopenia; Cytopenia; Hemorrhagic Disorders; Leukocyte Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked; Primary Immunodeficiency Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Lauri M. Burroughs, MD

  Fred Hutchinson Cancer Center

  STUDY CHAIR

• David J. Rawlings, MD

  Department of Pediatrics, University of Washington-Seattle Children's Hospital

  STUDY CHAIR

• Luigi D. Notarangelo, MD

  National Institute of Allergy and Infectious Diseases, NIH

  STUDY CHAIR

• Alexandra H. Filipovich, MD

  Children's Hospital Medical Center, Cincinnati

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: February 13, 2014
• First Posted: February 17, 2014
• Study Start: February 2, 2014
• Primary Completion: May 1, 2019
• Study Completion: May 1, 2019
• Last Updated: August 10, 2020

Record last verified: 2020-08

Locations

US (38); CA (5)