Using T-Cell Alloreactivity and Chimerism to Guide Immunosuppression Minimization in Intestinal Transplantation

Eligibility Criteria

• * All patients actively listed as candidates for intestinal or multi-visceral transplant at the study site; while all patients who are actively listed in United Network for Organ Sharing (UNOS) for intestinal and/or multi-visceral transplantation, including those who have previously received a multi-visceral transplant and are re-listed, are eligible for participation, the following are examples of listing criteria suitable for enrollment in this clinical trial:
• * Short Bowel Syndrome (SBS) due to:
• * Trauma (multiple resections/explorations and/or vascular abdominal trauma superior mesenteric artery (SMA) / superior mesenteric vein (SMV) injuries)
• * Gastroschisis
• * Volvulus
• * Necrotizing Enterocolitis
• * Intestinal Atresia
• * Crohn's Disease
• * Hirschprung's Disease
• * Chronic Intestinal Pseudo-Obstruction
• * Malabsorption:
• * Microvillus Inclusion Disease
• * Tufting Enteropathy
• * Complete portomesenteric thrombosis with cirrhosis
• * Slow-growing, low-malignancy potential tumors infiltrating mesenteric root:
• * Gardner's Syndrome
• * Familial Adenomatous Polyposis
• * Desmoid Tumor with Intra-Abdominal Infiltration
• * Endocrine Tumors
• * Re-transplant candidates who lost the first graft to rejection or patients who have higher risk of toxicity from chronic long term immunosuppression (i.e., patients with chronic kidney disease)
• * Patient commits to planned follow up at a study site for the 48-month duration of study procedures
• * Age ≥18 years old and ≤65 years old
• * Subjects or capable of signing the informed consent document themselves
• * Active systemic infection with hemodynamic instability and/or sepsis
• * Patients with known immunodeficiency syndrome
• * Carcinoma with metastasis (except neuro-endocrine tumors, even in the presence of metastasis these patients may undergo multivisceral/cluster transplantation)
• * Severe cardiovascular and/or respiratory instability, as defined by requirement of pressors or ventilator
• * Severe cerebral edema, with radiologic findings of effaced sulci and/or herniation
• * Poorly controlled hypertension (systolic blood pressure \> 170 on at least 2 occasions), diabetes mellitus (HbA1c \> 8), or uncontrollable seizure disorders
• * Age \> 65 years
• * Documented history of non-compliance with medical therapy and follow-up
• * Substance addiction in the last six months
• * Psychosocial Instability: absence of a consistent reliable social support system
• * Significant or active psychiatric disorder associated with the inability to cooperate or comply with medical therapy
• * In the judgement of the clinical team, severely limited functional status with poor rehabilitation potential
• * Multi-organ failure and preceding CD34+ infusion
• * Pre formed panel reactive antibodies (PRA) mean fluorescein intensity (MFI) \> 5000 by Luminex
• * Patients who are pregnant or breast-feeding or intend to get pregnant during the study period
• * Patients who have developed moderate or severe rejection before post-transplant day 11
• * Vulnerable populations, such as incarcerated or institutionalized individuals
• * Subjects with clinical features suggestive of GVHD
• * Subjects who are hemodynamically unstable (i.e., requiring vasopressor support)
• * Female subjects of childbearing age and male patients who are not using and/or unwilling to use an effective method of birth control for the duration of the trial activities
• * History of previous hematopoietic progenitor cell (HPC) infusion or transplant of any kind. Note: Human leukocyte antigen (HLA) mismatch will not be one of the exclusion criteria