Optimal TBI Dose to Improve the Survival in Unrelated Matched Marrow Transplantation for Adult Patients with Severe Aplastic Anemia: Prospective De-Escalation Study of TBI Dose.

Abstract

Background and Objectives: Patients with severe aplastic anemia (SAA) who do not have suitably HLA-matched related donor generally receive immunosuppressive therapy (IST) as first-line treatment and are considered for transplantation from matched unrelated donor (MUD) if they fail to respond to IST. To determine the optimal total body irradiation (TBI) dose as conditioning regimen in unrelated marrow transplantation for adult SAA patients, we conducted a prospective study to evaluate minimal dose of TBI sufficient to achieve sustained engraftment when it is used in combination with fixed dose of cyclophosphamide (CY).Methods: Between May 1998 and December 2003 twenty-eight patients were enrolled with a median age of 23 years old (20–44). All patients were multiply transfused and had received 1 or 2 course of intensive IST. Conditioning regimen consisted of CY (120mg/kg) plus TBI and they were divided into 3 group according to the fractionated TBI dose: group 1 (1200 cGy, n=5), group 2 (1000 cGy, n=9), and group 3 (800 cGy, n=14). Donor/recipient pairs were matched for HLA-A, -B by serology and -DRB1 by low-resolution DNA typing (n=15) or HLA-A, -B, and -DRB1 by high-resolution typing (n=13). Patients received CsA+MTx (n=4) or FK506+MTx (n=24) as GVHD prophylaxis.Results: All patients except one (group 2) achieved sustained engraftment. The incidence of acute GVHD more than grade II was not significantly different (60% in group 1, 38% in group 2, and 43% in group 3), but chronic GVHD developed more frequently in group 1 and 2 (60% & 80%, respectively) compared to group 3 (15%). Patients who received 800 cGy (group 3) had significantly better survival than those 1000 and 1200 cGy (93% in group 3, 44% in group 2, and 40% in group 1; group 3 vs group 1 and 2, p<0.02).Conclusions: Thus, a TBI dose of 800 cGy in combination with CY (120mg/kg) was sufficient to allow for engraftment in adult patients with SAA who received MUD BMT. Outcome in patients who received 800 cGy of TBI was superior to survival that among patients 1000 and 1200 cGy.