• Incidence & quality of engraftment & hematopoietic reconstitution/Early transplant-related severe morbidity & mortality/Incidence & severity of acute & chronic GvHD/Quality of immune reconstitution following transplantation/Overall survival rate. [ Time Frame: 8 years ] [ Designated as safety issue: Yes ]
  

Patients with this disease are born with it and have a fragility of the genes (chromosomes) in all the cells of the body. The fragility of the chromosomes puts patients with FA at high risk for certain cancers. Patients with FA are especially at risk of having diseases of the blood and marrow systems. These include (1) aplastic anemia, a disease where there is a failure of the bone marrow to make blood cells and (2) myelodysplastic syndrome which is represented by a clone of cells of the marrow that becomes "malignant" and stops making adequate numbers of blood cells (it is also called preleukemia.) The progression of the myelodysplastic syndrome will lead to (3) acute leukemia.

If you have Fanconi anemia and suffer from aplastic anemia, myelodysplastic syndrome, or leukemia standard treatment with medications or chemotherapy alone is not likely to cure these problems.

An allogeneic blood or bone marrow (hematopoietic stem cell) transplant can be done to provide you with marrow or blood stem cells from a healthy donor that can develop a normal blood forming system. An allogeneic stem cell transplant can cure the problems of the marrow and blood system. It cannot cure the chromosome fragility of the whole body. When allogeneic stem cell transplants have been done for the treatment of FA 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.

In order for the stem cells to grow and to kill leukemia cells, patients must receive chemotherapy and radiation therapy. This preparation is called cytoreduction. For patients with Fanconi anemia, the standard preparation for stem cell transplantation has been the use of total body irradiation (at a lower dose because of the high risk of side-effects) and a chemotherapy agent called cyclophosphamide (or Cytoxan) also at lower dose. While this has worked well with transplants from matched siblings, it was not enough in transplants from unrelated or cord blood donors and led to a high risk of rejection. In the last few years a medication called fludarabine was used successfully in transplants to give more immunosuppression and kill T-cells. Fludarabine allowed transplants to be done with low risks of rejection, and probably as importantly little risks of added side-effects. The addition of antithymocyte globulin to TBI, cyclophosphamide and fludarabine has made the chances of rejection very low.