The combined effect of total body irradiation (TBI) and cyclosporin A (CyA) on the risk of relapse in patients with acute myeloid leukaemia undergoing allogeneic bone marrow transplantation

One hundred and fifty acute myeloid leukaemia (AML) patients in first remis sion received an allogeneic bone marrow transplant (BMT), after conditionin g with cyclophosphamide 120 mg/kg and total body irradiation (TBI) 3.3 Gy x 3 (total nominal dose 9.9). The received dose, as recorded by thermolumine scent dosimeters, ranged between 7.83 and 12.25 Gy. Patients who received T BI <9.9 Gy (n = 34) had a significantly higher relapse rate when compared w ith patients receiving greater than or equal to 9.9 Gy (n = 116) (43% vs, 1 9%; P = 0.002). Graft versus host disease (GvHD) prophylaxis consisted of c yclosporin A (CyA) with or without methotrexate (MTX). The dose of CyA was either 1 or 5 mg/kg/day i.v. from day -1 to + 20, then 10 mg/kg/day orally until day + 365. Patients receiving 5 mg/kg CyA (n = 40) had a higher risk of relapse (49% vs. 15%: P = 0.0001). Thus, low-dose TBI (<9.9 Gy) and high -dose CyA (5 mg/kg) were significant predictors of leukaemia relapse. Patie nts were then divided into three groups: those who had both negative predic tors (<9.9 Gy TBI and 5 mg/kg CyA: n = 26); those who had only one (either <9.9 Gy TBI or 5 mg/kg CyA; n = 22); and those who had neither (greater tha n or equal to 9.9 Gy TBI and 1 mg/kg CyA; n = 102), The three groups were c omparable for FAB subtype, interval diagnosis transplant and age. The 5-yea r actuarial relapse rate for these three groups of patients was 49%, 41% an d 15%, with no difference between the first two and a significant differenc e when compared with the latter (P < 0.01), These data indicate that acute myeloid leukaemia can be cured with allogeneic bone marrow transplantation given an intensive conditioning regimen and low-dose immunosuppression post -graft, Either alone is insufficient to produce long-term disease-free surv ival. These results may be relevant for programmes of reduced intensity con ditioning designed for patients with acute leukaemia.