CNS Irradiation in Pediatric Acute Myleoid Leukemia: Equal Results by 12 or 18 Gy in Studies AML-BFM98 and 2004

Background. The impact of preventive central nervous system irradiation (CNS-RT) in childhood acute myeloid leukemia (AML) is still discussed. As results of study AML-BFM87 revealed an increased risk for relapse when CNS-RT was not performed, studies AML-BFM98 and -2004 randomized CNS-RT of 18 or 12 Gy in order to evaluate the efficacy of the lower dose and to reduce late effects. Procedures. To achieve a power of 80% for non-inferiority (range 11%) 240 patients per group were required. Out of 722 eligible patients, 486 patients < 18 years were randomized to receive 12 Gy (n = 249) or 18 Gy (n = 237). Since this was a non-inferiority study, the analysis was performed for treated (12 Gy: n = 252 and 18 Gy: n = 219). Results. Five-year survival, event-free survival and cumulative incidence of relapse were similar in patients who received 12 or 18 Gy, respectively (82 +/- 3% vs. 79 +/- 3%, 68 +/- 3% vs. 63 +/- 3%, and 30 +/- 3% vs. 34 +/- 3%). The lower limit of the one-sided confidence interval for the 5% difference in 5-years pEFS was 2%. There were six relapses with CNS involvement (one in the 12 Gy, and five in the 18 Gy group). Conclusion. Results demonstrate no disadvantage for patients irradiated with a reduced CNS dose of 12 Gy. Pediatr Blood Cancer 2011; 57: 986-992. (C) 2011 Wiley-Liss, Inc.