Patients who are born with Fanconi anemia have a fragility of their chromosomes that places them at increased risk of developing certain diseases, especially those of the blood and bone marrow. These include: (1) aplastic anemia, a disease in which there is a failure of the bone marrow to make blood cells; (2) myelodysplastic syndrome, in which a clone of bone marrow cells becomes cancerous and stops making adequate numbers of blood cells (also called "preleukemia"); and (3) acute leukemia, which may develop when myelodysplastic syndrome has progressed.
Standard treatment with medications or chemotherapy alone is not likely to cure aplastic anemia, myelodysplastic syndrome, or leukemia in patients with Fanconi anemia. An allogeneic blood or bone marrow
(hematopoietic stem cell) transplant can be done to provide patients
with marrow or blood stem cells from a healthy donor, which can then
develop into a normal blood-forming system. While an allogeneic stem
cell transplant can cure the problems of the marrow and blood system, it does not cure the underlying chromosome fragility. When allogeneic stem cell transplants have been performed for the treatment of Fanconi anemia using stem cells from donors other than matched siblings, they have been associated with a high risk of rejection of the transplant and of a complication called graft-versus-host disease (GvHD, a serious side effect in which T cells from the donor attack the tissues of the recipient).
In order for donated stem cells to take and to kill leukemia cells, patients must receive chemotherapy and radiation therapy. This process is called cytoreduction. For patients with Fanconi anemia, cytoreduction before stem cell transplantation has included the use of low-dose total body irradiation and low doses of a chemotherapy agent called cyclophosphamide (or Cytoxan). While this approach has worked well with transplants from matched siblings, it has not worked well enough in transplants from unrelated or placental cord blood donors, and has led to a high risk of transplant rejection. In the last few years, a medication called fludarabine has been used successfully in transplants to provide more immunosuppression and kill donor T cells. Fludarabine allowed transplants to be done with low risks of rejection, with few added side effects. The addition of antithymocyte globulin to total body irradiation, cyclophosphamide, and fludarabine has also reduced the chances of transplant rejection.
The purpose of this research study is: (1) to determine if the
combination of low-dose total body irradiation, low-dose
cyclophosphamide, fludarabine, and a serum to suppress the immune system can allow selected stem cells to take and grow, (2) to determine if selected stem cells from the blood or marrow can take without causing GvHD, and (3) to evaluate the side effects of the combination of low-dose radiation and chemotherapy drugs used for these transplants.
