CNS irradiation in pediatric acute myleoid leukemia: Equal results by 12 or 18 Gy in studies AML‐BFM98 and 2004

Abstract

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 patients as 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.