Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy for hematological malignancies as well as refractory autoimmune diseases such as systemic lupus erythematosus (SLE) (Shizuru 2004; Sullivan 2004; Sykes 2005). HCT results in allogeneic hematopoietic chimerism. For subjects with hematological malignancies, HCT allows for administration of higher and more potentially effective dosages of chemotherapy and radiotherapy. For subjects with abnormal nonmalignant lymphohematopoietic systems, HCT allows for replacement of the abnormal lymphohematopoietic system with a healthy one. HCT is often referred to as bone marrow transplantation (BMT). However, hematopoietic stem cells for use in HCT can be collected from bone marrow, peripheral blood, or umbilical cord blood.
In classical HCT, recipients are conditioned with total body irradiation (TBI) and/or high dose chemotherapy. However, both TBI and chemotherapy are highly toxic, even at reduced intensity. In addition, TBI and chemotherapy play a critical role in initiating graft versus host disease (GVHD) (Ferrara 2004). Toxicity and GVHD have limited the application of HCT. Therefore, there is a need for improved methods of conditioning a recipient for HCT.