Allogeneic blood and marrow transplantation remains the only viable cure for children who
suffer from many serious non-malignant hematological diseases. Transplantation, however,
carries a high risk of fatal complications. Much of the risk stems from the use of high dose
radiation and chemotherapy for conditioning, the treatment administered just prior to
transplant that eliminates the patients' marrow and immune system, effectively preventing
rejection of the donors' cells. Attempts to make blood and marrow transplantation safer for
children with non-malignant diseases by using lower doses of radiation and chemotherapy have
largely failed because of a high rate of graft rejection.
In many such cases, it is likely that the graft is rejected because the recipient is
sensitized to proteins on donor cells, including bone marrow cells, by blood transfusions.
The formation of memory immune cells is a hallmark of sensitization, and these memory cells
are relatively insensitive to chemotherapy and radiation. Alefacept, a drug used to treat
psoriasis, on the other hand, selectively depletes these cells. The investigators are
conducting a pilot study to begin to determine whether incorporating alefacept into a low
dose conditioning regimen can effectively mitigate sensitization and, thereby, prevent
rejection of allogeneic blood and marrow transplants for multiply transfused children with
non-malignant hematological diseases.