Title
Primary Immune Regulatory Disorders (PIRD): Longitudinal Study of Clinical Presentation, Treatment and Outcomes

Description
Primary Immune Regulatory Disorders (PIRD): Longitudinal Study of Clinical Presentation, Treatment and Outcomes

Objective
Primary Objective: The primary objective of this study is to estimate the overall survival (OS) of PIRD patients from the time of diagnosis. Patients may be treated with Best Available Therapy (BAT) or Hematopoietic Cell Transplant (HCT).

Secondary Objectives:
1. For HCT, determine the natural history of disease presentation, spectrum of symptoms, timing of HCT, and factors that prompt care providers to refer PIRD patients for HCT.
2. Determine the impact of treatment (BAT or HCT) on clinical outcome, including survival,
autoimmunity, inflammatory disease, non-malignant lymphoproliferation, immune reconstitution, infections, malignancy, and growth and development.
3. For HCT, determine donor chimerism after HCT and correlate this to resolution of PIRD-associated clinical symptoms and survival.
4. For HCT, determine the effect of stem cell source, donor matching and conditioning intensity on donor cell engraftment, donor chimerism, GvHD, survival after HCT, and resolution of PIRDassociated clinical symptoms.
5. For HCT, determine event-free and morbidity-free survival after HCT and determine whether active autoimmunity or autoinflammation at the time of HCT affects survival and outcome at 1, 2, 3, 5, 10 and 15 years post-HCT.
6. Determine predictors of disease response and survival after BAT and HCT. Determine whether these are broadly predictive or only applicable to patients with particular genetic defects.
7. Determine health-related quality-of-life (HRQoL) in patients with PIRD and whether this is impacted by treatment with BAT or HCT.
8. Determine the immunophenotype of T cells, Treg cells, and B cells in patients with PIRD and determine how this is affected by treatment (BAT or HCT).
9. Determine the genetic basis of disease in PIRD patients who meet clinical criteria for enrollment and do not have an identified genetic lesion.

Treatment This is a longitudinal study of patients with Primary Immune Regulatory Disorders (PIRD) (Study Arm), and family members of subjects enrolled on the Longitudinal Study Arm, who have not yet developed clinical disease (Family member cohort).

Key Eligibility Inclusion Criteria: The Longitudinal Study Arm will enroll subjects having confirmed PIRD, and will consist of a Retrospective Cohort, and a Prospective Cohort. A Diagnosis (Dx) date will be established for each patient as the time when the patient first meets/met the eligibility criteria for enrollment, even if this was in the past. The Diagnosis (Dx) date will start the clock for collection of data for the study, for all patients on the Longitudinal Study Arm.

Patients may be treated with Best Available Therapy (BAT) (includes any non-transplant therapies), or with Hematopoietic Cell Transplant (HCT).

If patients undergo Hematopoietic Stem Cell Transplant (HCT), the timing of the subsequent data collection windows will shift and will be established from the “HCT Date”.

Applicable Disease Sites
Hematologic cancers, other

Participating Institutions
UW Health University Hospital