Nonmyeloablative Allo Stem Cell Transplant for Severe Autoimmune Diseases

This is an interventional treatment trial for Systemic Lupus Erythematosus focused on measuring severe autoimmune diseases, allogeneic stem cell transplant Read More

Patient Inclusion Criteria:

• Performance status must be CALGB PS 0, 1, or 2 (or Karnofsky 40-100%)
• Patients must have a 6/6 HLA-matched related donor who is evaluated and deemed able to provide PBSCs and/or marrow by the transplant team.

• Patients must meet the following laboratory parameters (unless due to disease status as determined by the treating physician):

  • Hepatitis A, B and C status will be tested prior to therapy, but results will not exclude patients from participation (if positive, patients will be told they are at higher risk of adverse effects from allogeneic transplantation).
  • Bilirubin less than 6 times the upper limit of normal
  • Liver transaminases (AST, ALT) and alkaline phosphatase less than 10 times the upper limit of normal (unless due to active myositis)
  • Patients with a creatinine greater than 2.5 times the upper limit of normal are eligible, but will be told that they are at greater risk for kidney damage that could possibly result in temporary or even permanent dialysis.
• Patients of childbearing potential must agree to use some form of adequate birth control during the periods they receive chemotherapy and any post-chemotherapy medications related to the transplant. Females of child bearing potential must have a negative serum B-HCG within 1 week of starting therapy.
• Patients between the ages of 18 and 69, inclusive are eligible for this trial.
• Patients must also have a resting MUGA (preferred) or ECHO and PFTs with DLCO performed before transplant and found to be acceptable according to the treating institution's guidelines. Recommended minimum standards include an EF greater than 35% and corrected DLCO greater than 35% for this less toxic regimen. If lower than this, single patient exemption may be sought.
• Patients must have both a disease-specialist (rheumatologist/immunologist, or neurologist) physician and a bone marrow transplant physician evaluation at the treating center before a patient is considered eligible. Both specialists must agree that the patient is a candidate for transplantation and patients with SLE must have failed standard therapies.

Exclusion Criteria:

• Pregnant or lactating women
• Active uncontrolled infection
• Patients who are serologically true-positive for HIV
• Patients with other major medical or psychiatric illnesses, which the treating physician feels, could seriously compromise tolerance to this protocol
• Uncontrolled hypertension (BP > 100 diastolic despite treatment with maximum doses of at least 3 simultaneous or concurrent antihypertensives over a 2-month period)
• Uncontrolled malignant arrythmias or clinical evidence of congestive heart failure (New York Class IV)

6/6 HLA-Matched Related PBSC Donor Inclusion/Exclusion Criteria:

• Adult donors must be capable of providing informed consent; Potential donors under the age of 18 must have a 'single patient exemption' approved by the IRB and the donor and a guardian must provide assent.
• Donor must be 6/6 HLA matched, and related to the patient.

• Donor must not have any medical condition which would make apheresis and G-CSF administration more than a minimal risk, and should have the following:

  1. Adequate cardiac function by history and physical examination. Those with a history of cardiac problems should undergo a stress evaluation or be evaluated by a cardiologist and deemed eligible to donate.
  2. bilirubin and hepatic transaminases < or equal to 2.5 x ULN,
  3. adequate hematologic parameters including a hematocrit > 35% for males and 33% for females, white blood cell count of > or equal to 3,000, and platelets > or equal to 80,000.
  4. Donors with a known allergy to E. coli-derived products are ineligible for mobilization with G-CSF.
• Females of childbearing potential should have a negative serum beta-HCG test within 1 week of beginning G-CSF.