Central Nervous System Disease and Outcome in Pediatric Acute Myeloid Leukemia: Results from NOPHO-DBH AML2012 Trial

Background: Central nervous system disease (CNS3) in pediatric acute myeloid leukemia (pAML) is reported in 6% to 29% of cases. However, its impact on event-free survival (EFS) and overall survival (OS) remains uncertain. This study evaluates the effect of CNS involvement at diagnosis on relapse and survival in patients treated on the NOPHO-DBH AML2012 protocol. Methods: Data from 931 pediatric AML patients in the NOPHO-DBH AML2012 protocol were analyzed, comparing outcomes, relapse rates, and survival between those with and without CNS disease. CNS-directed therapy included intensified intrathecal chemotherapy without irradiation. Results: Of 922 patients with available CNS status, 10.9% had CNS3 at diagnosis. CNS3 patients were younger (median age 3.5 vs. 8 years,P=0.001) with higher white blood cell counts (56.1x10 ⁹ /L vs 18.7x10 ⁹ /L,P<0.001) and higher frequency of other extramedullary disease (30.4% vs 11.3%,P<0.001) and inv(16)(P<0.001). EFS _5y was 71.5% for CNS-positive patients vs. 62.7% for CNS-negative (p=0.14), and OS _5y was 81.4% vs. 79.3% (p=0.54). Patients with CNS disease had a lower cumulative incidence of relapse (15.6% vs 26.5%,P=0.023), and CNS relapse occurred in 0.9% and 0.7% of patients with and without CNS disease. Conclusion: CNS disease at diagnosis in pAML does not adversely affect survival or treatment response.