Transplantation of Partially Mismatched Related or Matched Unrelated Bone Marrow for Patients With Refractory Severe Aplastic Anemia

A Phase II Trial of Non-Myeloablative Conditioning and Transplantation of Partially HLA-Mismatched/Haploidentical Related or Matched Unrelated Bone Marrow for Patients With Refractory Severe Aplastic Anemia and Other Bone Marrow Failure Syndromes

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.

This research is being done to find out if bone marrow transplantation (BMT) followed by chemotherapy will help people with aplastic anemia who have failed other treatments.

You have a severe, life threatening disease (severe aplastic anemia) in your bone marrow. Your disease has come back or not responded after receiving one or more immunosuppressive treatments. High dose chemotherapy followed by bone marrow transplantation (BMT) has been used to treat blood diseases like yours but complications from Graft vs. Host disease (GVHD) and graft failure have limited the survival for those people.

A small study done at Johns Hopkins has shown that in subjects with other diseases (blood cancers) some immunosuppressive drugs given after the BMT have decreased how often subjects had complications of GVHD and engraftment failure.

People with aplastic anemia who have refractory disease (not responding to standard treatment) may join.

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)