Non-Total Body Irradiation (TBI) Containing Preparative Regimen in Alternative Donor Bone Marrow Transplantation (BMT) for Severe Aplastic Anemia (SAA).

Most preparative regimens in alternative donor BMT for SAA have included TBI to overcome high incidence of graft rejection, which is the major problem in this setting. With routine use of irradiated leukocyte-poor blood products, however, the incidence of graft rejection due to pre-transplant allo-sensitization has decreased. Recently, efforts to reduce dose intensity of the preparative regimen for alternative donor transplants have been made with promising results. Using non-TBI containing preparative regimens, 13 patients with SAA were transplanted from alternative donors in our center and we report on the results of BMT in these patients. Median age of the patients, 6 males and 7 females, was 22 years (range, 15-34). Twelve donors were unrelated volunteers and one was an HLA one-locus mismatched sibling. Median time from diagnosis of SAA to BMT was 304 days (range, 49–5,403). Nine patients had received one cycle of immunosuppressive treatment with ATG (± cyclosporine) before BMT, while 4 had not. All patients except one had been transfused before BMT. Preparative regimens consisted of cyclophosphamide (50 mg/kg x 4) plus ATG (Atgam^® 30 mg/kg x 3) in 9 patients, cyclophosphamide (50 mg/kg x 4) plus fludarabine (30 mg/m² x 3) in 2 patients, and cyclophosphamide (50 mg/kg x 2) plus fludarabine (30 mg/m² x 5) plus ATG (Atgam^® 30 mg/kg x 3 or Thymoglobuline^® 3 mg/kg x 3) in 2 patients. All patients received non-T-cell depleted bone marrow graft form the donor. Cyclosporine plus methotrexate were given for GVHD prophylaxis. All patients engrafted on a median of day 21 (range, 15–27) with complete donor chimerism. Grade III-IV acute GVHD developed in 3 (23%) of 13 patients and extensive chronic GVHD in 4 (31%) of 12 evaluable patients. With a median follow-up duration of 1,138 days (range, 118–1,553), 10 patients are alive with durable engraftment showing 75% of survival rate. Causes of death were chronic GVHD in 2 and CNS bleeding in 1. In conclusion, non-TBI containing preparative regimen could ensure durable engraftment in alternative donor BMT for SAA and showed promising results.