A Study of Patients Treated for Chronic Granulomatous Disease Since 1995

Overview

About this study

Chronic granulomatous disease (CGD) is an inherited immune system abnormality in which bone marrow transplantation has been shown to be curative. However the risks of transplantation are high and not all patients with CGD may need to undergo this high risk procedure. The purpose of this study is to determine the long term medical condition and daily functioning of patients with CGD after a transplant and if possible, compare these results to patients who do not undergo a transplant.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

Inclusion Criteria:

  • Participant Inclusion Criteria (Part 1 - Longitudinal Analysis)
    • CGD Patients Undergoing Transplant 1995 to Present with Birth Year In or After 1988
      • CGD Patients will be defined by both Defective Neutrophil NADPH Oxidase Function and by clinical history consistent with CGD
      • Patients must have both a functional assay demonstrating abnormal NADPH oxidase function and clinical history consistent with CGD 
        • Assay I Dihydrorhodamine (DHR)
        • Assay II Nitroblue Tetrazolium Oxidation Test (NBT)
        • Diagnostic of CGD (reported as reduced granulocyte oxidative response)
        • Report must be de-identified and provided
      • Clinical History where either functional assay or history is equivocal, one or more of the following may be used to confirm a diagnosis of CGD
        • Absent, significantly reduced expression, or abnormal size of  any of the 5 phox components (gp91 phox, p47 phox, p22 phox, p67phox, and p40phox) of NADPH oxidase, by either  molecular diagnosis (gene sequencing and expression analysis) or blood sample assay which demonstrates CGD with a stimulation index (SI) SI < 35 or equivalent
        • Assay report, including mean fluorescence intensity (MFI) from unstimulated and stimulated samples and gating strategy, must be de-identified and provided
      • Severe and/or recurrent infection (liver, perirectal or lung abscess, pneumonia, adenitis, or osteomyelitis) due to Staphylococcus aureus, Burkholderia, Serratia marcescens, non-albicans Candida, Aspergillus or other mold; or Nocardia or other deep tissue infection characteristic of CGD
      • Sterile granulomatous disease in respiratory, gastrointestinal or urogenital tracts; or Crohn's disease-like colitis
      • A family history consistent with either X-linked or autosomal recessive CGD
      • Western blot
      • Northern blot OR D. Mutation in a gene encoding one of the 5 phox components (gp91 phox, p47 phox, p22 phox, p67 phox, and p40 phox) of NADPH oxidase that is predictive of a decreased or absent oxidative burst (Nonsense, frameshift, or previously described missense mutation associated with CGD)
  • Prospective Cohort Patients who are to undergo transplantation during the study period must be further characterized as oxidase-null or oxidase positive by level of oxidase production by either
    • Genetic sequencing reporting a mutation that is unequivocally associated to absent oxidase production (e.g. null mutations) will be classified as oxidase-null CGD
    • Retrospective Cohort Patients who have already been transplanted will be included regardless of whether further characterization by oxidase level (or genotype/mutation data) is possible or not.
    • DHR assay stimulation Index
      • SI ≤ 2.5 will be classified as oxidase-null CGD
      • SI > 2.5 will be classified as oxidase positive CGD
      • A single validated test that is accepted by the PID-CGD Review Panel is adequate, but testing on two occasions for validation is desirable
    • Ferricytochrome C reduction assay of granulocytes with O2 < 2.3 nmoles /106 cells/h classified as oxidase-null CGD
      • A single validated test that is accepted by the PID-CGD Review Panel is adequate, but testing on two occasions for validation is desirable
  • Retrospective Cohort Patients who have already been transplanted will be included regardless of whether further characterization by oxidase level (or genotype/mutation data) is possible or not
  • Non-Transplanted CGD Patients with Birth Year In or After 1988
    • A non-transplant (conventional therapy) group of CGD subjects will be enrolled in the longitudinal study
    • The non-transplant subjects will be selected from the potentially eligible (retrospective) patient cohort with diagnosis of CGD treated with conventional non-transplant therapy
    • Participating sites will enter their entire retrospective cohort of CGD patients having birth year in or after 1988 into the registration cohort for this protocol
    • Baseline for both non-transplant subjects and HCT subjects for the purpose of comparing survival will be the year of birth.
    • For non-transplant subjects, many of the detailed analyses such as infection and autoimmune complication rates will be assessed in the year preceding the date of last contact
  • To participate in the Cross-Sectional Analysis, patients must have previously been enrolled into the Longitudinal Analysis of Protocol 6903
    • All transplanted subjects in the Cross-Sectional Analysis are surviving
    • Have at least 3 years of follow-up post-transplant
    • Non-transplanted CGD subjects will become eligible for consideration for the Cross-Sectional Analysis if they were eligible and enrolled in the retrospective cohort of the Longitudinal Analysis, and if/when they are > 3 years post-diagnosis of CGD
    • Provision of written informed consent will be required for the Cross-Sectional Analysis

Exclusion Criteria:

  • Participant Exclusion Criteria (Longitudinal and Cross- Sectional Analyses)
    • Presence of other primary immunodeficiency syndromes that do not meet the clinical and laboratory criteria for CGD
    • Rac2 Deficiency
    • Myeloperoxidase Deficiency (MPO Deficiency)
    • Glutathione deficiency
    • Leukocyte adhesion deficiency syndrome
  • Non-transplant subjects
    • The above exclusions pertain
    • In addition, non-transplant subjects will be excluded if the only assessment of oxidase function available is the nitroblue tetrazolium (NBT) test (a non-quantitative test)

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Avni Joshi, M.D.

Open for enrollment

Contact information:

Joni Amundson

(507)293-5606

amundson.joni@mayo.edu

More information

Publications

  • Allogeneic hematopoietic cell transplantation (HCT) has been used for 40 years to ameliorate or cure primary immune deficiency (PID) diseases, including severe combined immunodeficiency (SCID) and non-SCID PID. There is a critical need for evaluation of the North American experience of different HCT approaches for these diseases to identify best practices and plan future investigative clinical trials. Our survey of incidence and prevalence of PID in North American practice sites indicates that such studies are feasible. A conference of experts in HCT treatment of PID has recommended (1) a comprehensive cross-sectional and retrospective analysis of HCT survivors with SCID; (2) a prospective study of patients with SCID receiving HCT, with comparable baseline and follow-up testing across participating centers; (3) a pilot study of newborn screening for SCID to identify affected infants before compromise by infection; and (4) studies of the natural history of disease in patients who do or do not receive HCT for the non-SCID diseases of Wiskott-Aldrich syndrome and chronic granulomatous disease. To accomplish these goals, collaboration by a consortium of institutions in North America is proposed. Participation of immunologists and HCT physicians having interest in PID and experts in laboratory methods, clinical outcomes assessment, databases, and analysis will be required for the success of these studies. Read More on PubMed

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20207446

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