Hematopoietic Stem Cell Transplantation (HSCT) for Common Variable Immunodeficiency (CVID) and Other Autoimmune Manifestations of Primary Immune Regulatory Disorders (PIRD)
This is a research protocol that will examine Hematopoietic Stem Cell Transplantation (HSCT) using a reduced conditioning regimen (RIC) with total body Irradiation (TBI) in those diagnosed with Common Variable Immunodeficiency (CVID) and Other Autoimmune Manifestations of Primary Immune Regulatory Disorders (PIRD).
• Patient, parent, or legal guardian must have given written informed consent. For pediatric subjects who are developmentally able, assent or affirmation will be obtained.
• Male or female, 5 through 40 years old, inclusive, at the time of informed consent.
• Patients must have evidence of common variable immunodeficiency (CVID) or other autoimmune manifestation of a primary immune regulatory disorder (PIRD). Genetic screening is required by a targeting gene panel to determine presence of genetic variations that may lead to inborn errors of immunity.
• Examples of such diseases include, but are not limited to:
⁃ Common variable immunodeficiency (CVID)
⁃ Combined Immunodeficiency (CID)
⁃ Immune dysregulation polyendocrinopathy enteropathy X-linked (IPEX syndrome), IPEX like syndromes
⁃ Combined immunodeficiency with defects in T-cell-mediated immunity, including Omenn syndrome and DiGeorge Syndrome
⁃ Chronic Granulomatous Disease (CGD)
⁃ Signal Transducer and Activator of Transcription (STAT 1) Gain of Function (STAT1 GOF)
⁃ Hypomorphic Recombination-Activating Genes (RAG) 1 and RAG 2
⁃ CD40 or CD40L deficiency
⁃ Mendelian Susceptibility to Mycobacterial Disease
⁃ GATA-binding factor 2 (GATA2) Associated Immunodeficiency
⁃ Mouth and Genital Ulcers with Inflamed Cartilage Syndrome (MAGIC)
• Must have previously failed, due to lack of response or intolerance, mycophenolate mofetil and a B cell-depleting antibody, such as Rituximab
• Glomerular Filtration Rate (GFR) ≥50 mL/min/1.73 m2
• Aspartate Aminotransferase (AST) ≤4x upper limit of normal
• Alanine Aminotransferase (ALT) ≤4x upper limit of normal
• Direct bilirubin ≤ 2.5 mg/dL
• Human Immunodeficiency Virus (HIV) negative by serology and PCR
⁃ Human T-cell Lymphotropic Virus (HTLV) negative by serology
⁃ Cardiac ejection fraction ≥ 40% or shortening fraction ≥26%
⁃ Forced Vital Capacity (FVC) and Forced Expiratory Volume in 1 second (FEV1) ≥40% predicted for age
⁃ Peripheral Capillary Oxygen Saturation (SpO2) of \>92% at rest on room air
⁃ Subjects must be a minimum of 8 weeks post-solid organ transplant prior to start of conditioning, if applicable
⁃ Negative pregnancy test for females \>10 years old or who have reached menarche, unless surgically sterilized.
⁃ All females of childbearing potential and sexually active males must agree to use a FDA approved method of birth control for up to 12 months after stem cell transplant or for as long as they are taking any medication that may harm a pregnancy, an unborn child or may cause birth defects.
⁃ Subject and/or parent guardian informed of the potential risks of infertility following stem cell transplant and advised to discuss sperm banking or oocyte harvesting.
⁃ Transplant endorsement from clinical immunologist