Trial Information

Reduced-Intensity Preparative Regimen for Allogeneic Stem Cell Transplantation in Patients With Severe Aplastic Anemia

Aplastic Anemia is a blood disorder where bone marrow does not produce enough cells for
blood. Patients with aplastic anemia have lower counts of all three blood cell types (RBC,
WBC, and Platelet). Severe cases of aplastic anemia that are untreated can lead to death
from bleeding and overwhelming infection.

For patients with Severe Aplastic Anemia (SAA), allogeneic hematopoietic stem cell
transplant (HSCT) from an HLA-identical sibling is an accepted treatment for restoring
normal bone marrow function. Preparative regimens for allogeneic HSCT are designed to give
the highest tolerated doses of chemotherapy, with or without total body irradiation (TBI),
in order to fully "ablate" or destroy the patient host's bone marrow so that the
transplanted cells from the HLA-identical sibling can engraft in the patient host.

While allogeneic HSCT has been proven to be a curative form of therapy for SAA, it is also
associated with high transplant-related morbidity (side effects) and possible mortality
(death). One of the toxic side effects from high-dose chemotherapy and TBI are believed to
be a major contributing factor to "Graft-versus-Host Disease" (GVHD).

Preliminary studies have shown that a reduced intensity (non-myeloablative) allogeneic HSCT
may be just as effective in treating SAA. Low-dose chemotherapy is used instead of high-dose
chemotherapy and TBI. Some smaller studies have indicated that reduced intensity
preparative regimens using Fludarabine and Cyclophosphamide allowed engraftment in the
matched sibling donor setting with an acceptable level of toxic side effects in subjects
with a variety of hematologic cancers. Additional studies that followed showed that a
reduced intensity preparative regimen that included fludarabine, cyclophosphamide and
antithymocyte globulin, allowed engraftment of donor stem cells in subjects with SAA with
acceptable engraftment rates and a decrease in the severity of GVHD.

This study is designed to evaluate the effectiveness of allogeneic transplant after a
reduced-intensity preparative regimen, to evaluate survival, and to evaluate the side
effects including GVHD of this treatment. Patients will be in the study for two years for
treatment and active monitoring. All patients will be followed until death.