Fludarabine, Cyclophosphamide, Anti-Thymocyte Globulin, with or without “ 2Gy TBI, for Alternative Donor Transplants in Acquired Aplastic Anemia (SAA): A Report From the EBMT-SAA Working Party.

Data from 100 patients with acquired severe aplastic anemia (SAA) undergoing an alternative donor transplant, were analyzed. Patients were prepared with a combination of fludarabine (30 mg/m 2×4), cyclophosphamide (300 mg/m 2×4), antithymocyte globulin (3.75 mg/lgx4) (FCA) (n=52, median age 13 years), or FCA supplemented with low dose (2 Gy) total body irradiation (FCA-TBI), but with a lower dose of ATG (total 7.5 mg/kg) (n=48, median age 27 years). The donor was unrelated (n?87) or a one antigen mismatched family donor (n=13).

Acute graft versus host disease (GvHD) grade III-IV was seen in 13% and 7% ; extensive chronic GvHD was recorded in 1 FCA patient and in 4 patients receiving FCA-TBI.

Rejection/graft failure was seen in 17 patients, equally distributed in the two groups: 9/17 patients survive long term, 3 with autologous recovery, and 6 after a second transplant.. As to predictors of graft failure, patients with a longer interval from diagnosis to transplant (> 2 years) had a trend for a higher risk of GF (22%) as compared to patients grafted <1 year (12%) or between 1-2 years (14%) (p=0.3).

within 100 days from BMT the average donor chimerism was 93% and 84% in the FCA and FCA-TBI regimens. Beyond day +100 the average was 89% and 80%.

With a median follow up of 1204 days, the overall actuarial 5 year survival is 75%, respectively 73% for the FCA and 79% for the FCA-TBI. The interval diagnosis-transplant (<1 year, 1-2 years and >2 years) was a significant predictor of survival in univariate and multivariate analysis : actuarial survival was 87%, 86%, 58% respectively (p=0.004). Older age and HLA mismatch was a significant predictor of survival in the FCA group, but not in the FCA-TBI patients.

Twentythree patients died, 13/52 in the FCA group and 10/48 in the FCA-TBI group (p=ns): major causes of death were rejection (n=7), post-transplant-lymphoproliferative-disease (n=4) and GvHD (n=4).

This study confirms a significantly improved outcome of alternative donor transplants in SAA patients, and suggests that best results are achieved if the transplant is performed within 2 years from diagnosis. FCA seems appropriate only for children with well matched donors, whereas FCA-TBI is preferable in adults, especially when the donor is HLA mismatched. Complications such as rejection and EBV reactivation need to be addressed with modifications of the transplant regimens.

No relevant conflicts of interest to declare.