What is the minimum adequate busulfan dose for patients with sickle cell disease undergoing reduced intensity conditioning with fludarabine, busulfan, and anti-thymocyte globulin?

Fludarabine busulfan anti-thymocyte globulin is a common conditioning chemotherapy with reduced toxicity used for transplantation in sickle cell disease (SCD). The dose of busulfan used in this protocol is variable across studies and centers. The minimum dose that maintains long-term donor chimerism is not well established. We hypothesized that a lower, less-toxic dose could be used to maintain adequate long-lasting chimeras, which might allow for the inclusion of older or comorbid patients with this disease. In our retrospective study of 11 patients, 8-9.6 mg/kg was adequate to maintain chimerism in six patients. A 6 mg/kg dose resulted in transplant rejection in two patients. This suggests that 0.8 mg/kg IV busulfan every 6 h for 8-12 doses (total 8-9.6 mg/kg) is the minimum adequate busulfan dose required to maintain long-lasting chimeras, facilitating the successful withdrawal of immunosuppression in SCD patients who receive this protocol.