Autologous Stem Cell Transplantation for Crohn's Disease

5.1 Inclusion Criteria

1. Subject and/or guardian must be able to understand and provide informed consent.

2. Male or female, 10 through 60 years old, inclusive at time of informed consent.

3. Examples of subjects for whom stem cell transplant therapy would be appropriate include, but are not limited to:

• Patients who have had prior surgery and subsequent severe recurrent disease in spite of aggressive maintenance therapy, necessitating consideration of further extensive surgical resections.

• Patients who have diffuse small bowel and colonic disease and who are refractory to aggressive medical treatment, and not eligible for treatment using a surgical approach without the risk of precipitating short bowel syndrome and dependence of parenteral nutrition or who have other conditions that preclude surgery

• Patients with a persistently high Harvey Bradshaw Index (HBI) (>6), CDAI (>250) or Pediatric CD Activity Index (PCDAI>45) (44) score or those in the lower, moderate range (HBI ≤ 6), (CDAI < 250), (PCDAI 30-45), but who are dependent on daily doses of corticosteroids, that are unable to be withdrawn, and aggressive medical treatment to maintain moderate disease status.

• Patients who have resistant complications of CD unresponsive to medical management including multiple enteric fistulas, enterovesicular or enterovaginal fistulas, severe perianal disease, debilitating arthritis, severe skin lesions (pyoderma), and severe bony complications of the disease and therapy (aseptic necrosis, pathologic fractures).

• Patients who developed severe complications to while receiving medical management such as pancreatitis following 6-Mercaptopurine, colitis following 5-ASA or those with severe hypersensitivity to TNFalpha inhibitors (infliximab, adalimumab, certolizumab pegol), anti-integrin agents (natalizumab, vedolizumab) or anti-IL12/23 agents (ustekinumab).

• Patients with stomas are eligible.

4. No surgical therapeutic option secondary to risk of short bowel syndrome or patient refusal.

5. Harvey Bradshaw Index (HBI) or CD activity score >5, CDAI >250 or PCDAI >30.

6. Platelet count greater than 100,000/mm3.

7. Absolute neutrophil count greater than 1500/mm3 (unless secondary to 6MP therapy).

8. Creatinine ≤ 2.0 mg/dL.

9. No history of coronary artery disease; resting LVEF ≥ 40% or shortening fraction ≥ 26%.

10. FEV1/FVC ≥ 60% predicted for age; DLCO ≥ 60% predicted value for age.

11. Negative pregnancy test for females ≥ 10 years old or who have reached menarche, unless surgically sterilized.

12. All females or childbearing potential and sexually active males must agree to use a FDA approved method of birth control for up to 24 months after PBSC transplant or for as long as they are taking any medication that may harm a pregnancy, an unborn child or may cause a birth defect.

5.2 Exclusion Criteria

1. Patients who have not been treated with adequate dosing of 6-MP, 5-ASA products and metronidazole.

2. Patients who achieved a sustained, corticosteroid free response to anti-TNF alpha therapy, anti-integrin therapy or anti-IL12/23 therapy after a 4 month course of treatment.

3. Toxic megacolon, intestinal perforation

4. Conjugated bilirubin > 2.0 mg/dL.

5. Pregnancy or nursing mother

6. HIV/HTLV seropositive, HBsAg, or HCV RNA positive by PCR

7. Active infection, as determined by the appropriate confirmatory testing e.g. blood cultures, PCR testing, etc., within two weeks of mobilization and high dose chemotherapy.

8. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.