Study of Treatment of Inflammation before Stem Cell Transplant in People with a Primary Immune Regulatory Disorder (PIRD) and/or an Autoinflammatory Condition, BRIDGE Study

Inclusion Criteria

• Patients receiving first allo-HCT for the following immunologic conditions: * Primary immune regulatory disorder with or without a genetic lesion as defined by the Primary Immune Deficiency Treatment Consortium (PIDTC) * Patients with autoinflammatory disorders evidenced by cytokine or inflammation assays with at least 1.5 x upper limit of normal (ULN) of measured cytokines and/or an elevated ferritin or erythrocyte sedimentation rate (ESR) > 2 ULN * For inclusion on the emapalumab group, the lesion must be isolated to the IFNγ pathway (or mediators thereof) with an elevated CXCL9 > 1.5 ULN OR sIL2R > 1.5 ULN (or already controlled on immune modulation, provided that CXCL9 or sIL2R levels were elevated prior to initiation of immune modulation). Inclusion on the fludarabine/dexamethasone group requires inflammation (as defined above) other than an isolated IFNγ pathway
• Able to tolerate cytoreduction (based on adequate organ function as described below)
• Patients of any age can enroll so long as they meet other inclusion criteria
• Serum bilirubin =< 2 mg/dL, unless benign congenital hyperbilirubinemia. Patients with hyperbilirubinemia related to paroxysmal nocturnal hemoglobinuria or other hemolytic disorders related to their primary immune regulatory disorder (PIRD) diagnosis are eligible
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase < 2.5 times the upper limit of normal unless thought to be disease-related. Investigator will need to perform clinically indicated evaluations to assess if disease related or intrinsic liver disease. Additional testing may be done if clinically indicated, after the pre-transplant immune prophase and prior to start of conditioning as this will provide additional data to confirm disease related versus intrinsic liver dysfunction
• Serum creatinine < 1.5x normal for age. If serum creatinine is outside the normal range, then creatinine clearance (CrCl) > 50 mL/min/1.73 m^2 (calculated or estimated) or glomerular filtration rate (GFR) (mL/min/1.72 m^2) > 30% of predicted normal for age * Age: 1 week; MeanGFR +/- standard deviation (SD) (mL/min/1.73 m^2): 40.6 + / - 14.8 * Age: 2 – 8 weeks; MeanGFR +/- standard deviation (SD) (mL/min/1.73 m^2): 65.8 + / - 24.8 * Age: > 8 weeks; MeanGFR +/- standard deviation (SD) (mL/min/1.73 m^2): 95.7 +/- 21.7 * Age: 2 – 12 years; MeanGFR +/- standard deviation (SD) (mL/min/1.73 m^2): 133 +/- 27 * Age: 13 – 21 years (males); MeanGFR +/- standard deviation (SD) (mL/min/1.73 m^2): 140 +/- 30 * Age: 13 – 21 years (females); MeanGFR +/- standard deviation (SD) (mL/min/1.73 m^2): 126.0 + / - 22.0
• Left ventricular ejection fraction (LVEF) >= 50% by multigated acquisition scan (MUGA) or resting echocardiogram
• Pulmonary function testing (forced expiratory volume in 1 second [FEV1] and corrected diffusion capacity of the lung for carbon monoxide [DLCO]) >= 50% predicted (pediatric patients unable to complete pulmonary function testing (PFTs) will need oxygen saturation as recorded by pulse oximetry of >= 92% on room air)
• Age >= 16 years: Eastern Cooperative Oncology Group (ECOG) =< 1 or Karnofsky 70%
• Age < 16 years: Lansky 70%
• Each patient must be willing to participate as a research subject and must sign an informed consent form or legal guardian with assent as appropriate
• DONOR: Related Donors: * 8/8 or 7/8 human leukocyte antigen (HLA) matched at A, B, C, and DRB1 loci, as tested by DNA analysis * Haploidentical donors at A, B, C and DRB1 loci, as tested by DNA analysis
• DONOR: Unrelated Donors: * 8/8 or 7/8 matched at A, B, C, and DRB1 loci, as tested by DNA analysis
• DONOR: Able to provide informed consent for the donation process per institutional standards
• DONOR: Meet standard criteria for donor collection (e.g. National Marrow Donor Program Guidelines or collecting center guidelines as approved by treating physician)

Exclusion Criteria

• Uncontrolled infection at the time of enrollment
• Patients who have undergone previous allo-HCT
• Patient seropositivity for human immunodeficiency virus (HIV) I/II and/or HTLV I/II
• Females who are pregnant or breastfeeding
• Patients unwilling to use contraception during the study period
• Patient or parent or guardian unable to give informed consent or unable to comply with the treatment protocol including research tests