Treatment of Fanconi anemia patients using fludarabine and low-dose total body irradiation followed by unrelated donor hematopoietic cell transplantation

A non-myeloablative conditioning regimen consisting of fludarabine (FLU) and 2 Gy total body irradiation (TBI) has been used with great experience and engraftment success without promoting excessive non-relapse mortality (NRM) in medically infirm patients requiring hematopoietic cell transplantation (HCT). Here, we studied this same low-toxicity regimen as a means to promote engraftment of unrelated donor peripheral blood stem cells (PBSC) in patients with Fanconi Anemia (FA). All patients tolerated the regimen well with no mucositis or other severe toxicity. Of six patients transplanted, five achieved stable mixed or full donor chimerism. Acute and chronic graft-versus-host disease (GVHD) occurred in four and three patients, respectively. Three patients are alive and well a median of 45.9 (range, 20.9–68.1) months after transplant. In summary, this FLU-based regimen facilitates stable engraftment of unrelated PBSC but is associated with significant chronic GVHD.