Transplantation of Partially Mismatched Related or Matched Unrelated Bone Marrow for Patients With Refractory Severe Aplastic Anemia
Condition: Severe Aplastic Anemia; Bone Marrow Failure Syndromes
MeSH terms: Anemia; Anemia, Aplastic; Bone Marrow Failure Disorders; Pancytopenia; Hemoglobinuria, Paroxysmal; Syndrome
Intervention: Bone marrow transplant; Thymoglobulin; Fludarabine; Cyclophosphamide; TBI; Mesna; Tacrolimus; Mycophenolic acid mofetil
Intervention description: Day 0; 0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7; 30 mg/M2 IV on days -6 to -2; 14.5 mg/kg IV on days -6, -5, 3, 4; 200 cGy on day -1; 40 mg/kg IV on days 3, 4; For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present; 15 mg/kg PO/IV TID beginning on day 5 through day 35
Intervention MeSH terms: Mycophenolic Acid; Cyclophosphamide; Fludarabine; Tacrolimus; Thymoglobulin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Maximum age: 73 Years
Healthy volunteers: No
Keywords: bone marrow transplant; thymoglobulin; cyclophosphamide; fludarabine; tacrolimus; Mycophenolic Acid Mofetil; chemotherapy; GVHD; haploidentical

Summary:

      Our primary objective is to determine if it is feasible for SAA patients to be transplanted
      using non-myeloablative conditioning and post transplantation cyclophosphamide with partially
      HLA-mismatched donors.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with relapsed or refractory SAA or very SAA defined:

               -  Bone marrow (< 25% cellular)

               -  Peripheral cytopenias (at least 2 of 3)

                    -  ANC < 500 per ml

                    -  Platelets < 20,000 per ml

                    -  Absolute retic < 60,000 or corrected retic < 1%

               -  Very severe: as above, but ANC < 200

               -  Disease may be designated as acquired or inherited if previous counts known
                  (these other bone marrow failure disorders that are characterized by aplastic
                  anemia may go by additional names such as dyskeratosis congenita or PNH)

               -  Failed at least one course of immunosuppressive therapy (if presumed acquired
                  disease). Patients with inherited disease will be characterized as refractory and
                  do not require immunosuppressive first.

          -  Age 0- upper age limit as determined by current institutional standards

          -  Good performance status (ECOG 0 or 1; Karnofsky and Lansky 70-100)

          -  Patients and donors must be able to sign consent forms (or if a minor the parent will
             sign). Donors should be willing to donate.

          -  Patients must be geographically accessible and willing to participate in all stages of
             treatment.

          -  Adequate end-organ function as measured by:

               1. Left ventricular ejection fraction > or = to 35%, or shortening fraction > 25%
                  (For pediatric patients, a normal ejection fraction is required)

               2. Bilirubin ≤ 3.0 mg/dL (unless due to Gilbert's syndrome or hemolysis), and ALT
                  and AST ≤ 5 x ULN

               3. FEV1 and FVC > or = to 40% of predicted; or in pediatric patients, if unable to
                  perform pulmonary function tests due to young age, oxygen saturation >92% on room
                  air

        Exclusion Criteria:

          -  Patients will not be excluded on the basis of sex, racial or ethnic background.

          -  Prior transfusions from selected donor (as this could have cause recipient
             alloimmunization against the donor)

          -  Women of childbearing potential who currently are pregnant (HCG+) or who are not
             practicing adequate contraception.

          -  Patients who have any debilitating medical or psychiatric illness that would preclude
             their giving informed consent or their receiving optimal treatment and follow up.

          -  Uncontrolled viral, bacterial, or fungal infections (HIV infection permitted if viral
             load undetectable)