Allogeneic Stem Cell Transplant for Patients With Severe Aplastic Anemia

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.

Sex

All

Minimum age

1 Minute

Maximum age

60 Years

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.