Allogeneic Stem Cell Transplant for Patients With Severe Aplastic Anemia
Condition: Aplastic Anemia
MeSH terms: Anemia; Anemia, Aplastic
Intervention: Cytoxan; Campath; Total Body Irradiation (TBI); FK-506; Methotrexate; Stem cell infusion
Intervention description: Cytoxan will be given at 50 mg/kg per dose for 4 successive days.; Campath will be given at a dose of 3 mg for patients whose weight is between 5 and 15 kg; at a dose of 5 mg for patients whose weight is between 16 and 30 kg; and at a dose of 10 mg for patients whose weight is greater than 30 kg. The last dose of Campath should be 24 hours or more before stem cell infusion.; TBI will be given at a dose of 200 cGy for 6/6 HLA match and at a dose of 400 cGy in two fractions of 200 cGy each for 5/6 HLA matched donor.; FK-506 will be given at a dose of 0.03 mg/kg/day via continuous infusion over 24 hours from 4pm on day -2 until engraftment or when patient is able to take by mouth (PO), then 0.03 mg/kg PO every 12 hours.; Methotrexate will be administered on day +1, day +3, day +6 and day +11 at a dose of 5 mg/m2. The day +11 dose may be omitted at the discretion of the bone marrow transplant (BMT) in-patient attending physician.; Where possible patients will receive bone marrow. Marrow will be collected as per National Marrow Donor Program (NMDP) guidelines to provide a volume of 15-20 ml/kg of marrow and/or 2-4 X 10^8 nucleated cells/kg. In case marrow cannot be collected, peripheral blood stem cell (PBSC) will be substituted. A minimum of 5-6 X 10^6 CD 34+ cells/kg should be collected, with a target of 10 X 10^6/kg.
Intervention MeSH terms: Cyclophosphamide; Methotrexate; Alemtuzumab; Tacrolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 1 Minute
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Severe Aplastic Anemia; Severe

Summary:

      Patients have been diagnosed with severe Aplastic Anemia that have not responded to treatment
      with immunosuppressive therapy (drugs that suppress the immune system, for example Steroids).
      The immune system is the system in the body that helps protect the body and fights bacterial,
      viral and fungal infections.

      Research studies have shown that patients with Aplastic Anemia have improved survival (may
      live longer) after receiving a HLA (Human Leukocyte Antigen) identical sibling (brother and
      sister) stem cell transplants. Patients who do not have matched siblings can undergo
      immunosuppressive therapy, which has also shown to improve outcome. Unfortunately patients
      who do not respond to immunosuppressive therapy usually die. The best chance of survival for
      these patients is an HLA matched unrelated or mismatched related stem cell transplant as
      described below.

      Stem cells are created in the bone marrow. They mature into different types of blood cells
      that people need including red blood cells which carry oxygen around the body, white blood
      cells which help fight infections, and platelets which help the blood to clot and prevent
      bleeding. For a matched unrelated stem cell transplant, stem cells are collected from a
      person (donor) who is not related to the patient but who has the same type of stem cells. For
      a mismatched related stem cell transplant, stem cells are collected from a donor who is
      related to the patient and whose stem cells are almost the same as those of the patient but
      not exactly. The patient then receives high dose chemotherapy. This chemotherapy kills the
      stem cells in the patient's bone marrow. Stem cells that have been collected from the donor
      are then given to the patient to replace the stem cells that have been killed.

      The major problems associated with these types of stem cell transplants are graft rejection
      (where the patient's immune system rejects the donor stem cells) and severe graft versus host
      disease (GVHD), where the donors stem cell reacts against the patient's tissues in the body.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Diagnosis of Severe Aplastic Anemia (SAA) based on bone marrow aspirate and biopsy
             results.

          2. Failure to respond to immunosuppressive therapy.

          3. Lack of an Human Leukocyte Antigen (HLA) identical family member.

          4. A 6/6 or 5/6 HLA matched unrelated donor or a 5/6 matched related donor available
             after high resolution HLA typing.

          5. Age from birth to 60 years.

        Exclusion Criteria:

          1. Severe disease other than aplastic anemia that would limit the probability of survival
             during the graft procedure. Patients who present with active infection must be treated
             to maximally resolve this problem before beginning the conditioning regimen.

          2. Human immunodeficiency virus (HIV) seropositive patients

          3. Patients who have clonal cytogenetic abnormalities or a myelodysplastic syndrome.

          4. Patient greater than 60 years of age.

          5. Women who are pregnant or nursing.

          6. Patients with active hepatitis

          7. Patients with severe cardiac dysfunction defined as shortening fraction < 25%.

          8. Patients with severe renal dysfunction defined as creatinine clearance < 40
             ml/mim/1.73m2.

          9. Patient with severe pulmonary dysfunction with forced expiratory volume in the first
             second (FEV1), forced vital capacity (FVC) and diffusing capacity of the lung for
             carbon monoxide (DLCO) 40% of predicted or 3 standard deviations (SD) below normal.