Hypodiploidy has Unfavorable Impact on Survival in Pediatric Acute Myeloid Leukemia:An I-BFM Study Group collaboration

Abstract

Hypodiploidy, defined as modal number (MN) 45 or lower, has not been independently investigated in pediatric acute myeloid leukemia (AML) but is a well-described high-risk factor in pediatric acute lymphoblastic leukemia. We aimed to characterize and study the prognostic impact of hypodiploidy in pediatric AML. In this retrospective cohort study we included children below 18 years of age with de novo AML and a hypodiploid karyotype diagnosed 2000 to 2015 from fourteen childhood AML groups from the international Berlin-Frankfurt-Münster (I-BFM) framework. Exclusion criteria comprised constitutional hypodiploidy, monosomy 7, composite karyotype, and t(8;21) with concurring sex chromosome loss. Hypodiploidy occurred in 81 patients (1.3%) with MNs 45 (n=66), 44 (n=10), and 43 (n=5). The most frequent chromosomes lost were 9 and sex chromosomes. Five-year event-free survival (EFS) and overall survival (OS) were 34% and 52% for the hypodiploid cohort. Children with MN≤44 (n=15) had inferior EFS (21%) and OS (33%) compared to children with MN=45 (n=66, EFS: 37%, OS: 56%). Adjusted Hazard ratios were to 4.9 (p=0.001) and 6.1 (p=0.003). Monosomal karyotype or monosomy 9 had particular poor OS (43% and 15%, respectively). Allogeneic stem cell transplantation (SCT) in first complete remission (CR1) (n=18) did not mitigate the unfavorable outcome of hypodiploidy (adjusted HR for OS was 1.5, p=0.42). We identified pediatric hypodiploid AML as a rare subgroup with an inferior prognosis even in patients treated with SCT in CR1.