Reduced-Intensity Bone Marrow Transplantation for Heavily Transfused Patients with Severe Aplastic Anemia - Japanese Single Center Experience.

Background: Bone marrow transplantation (BMT) is a curative therapy for severe aplastic anemia (SAA). Outcome of BMT can be negatively affected when there is organ damage such as heart failure, liver dysfunction and diabetes mellitus after multiple transfusions in patients with long-standing SAA. Multiple transfusions also sensitize SAA patients with alloantigens and place them at high risk of graft rejection; it is an important problem after BMT for patients with multiply transfused SAA. We investigated the use of the combination of fludarabine monophosphate (FLU), cyclophosphamide (CY) and anti-thymocyte globulin (ATG) as the conditioning regimen in heavily transfused SAA patients.

Methods: Four patients with heavily transfused SAA were treated with allogeneic BMT from unrelated and sibling donor. They were treated with a reduced-intensity conditioning regimen that included FLU (120 mg/m²), CY (1,200 mg/m²) and ATG (horse 40 mg/kg, rabbit 15 mg/kg).

Results: The regimen was well tolerated, and engraftment rapidly occurred with some therapy-related toxicity encountered. Chimerism analysis on day 30 after transplant showed reconstitution with 100% donor cells in three patients. Among these three patients, two patients showed late graft rejection. At this time of reporting, only one patient is alive with complete donor chimerism.

Conclusion: The combination of FLU/CY/ATG was well tolerated also in heavily transfused SAA patients: problems such as graft rejection remain.