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Prognostic impact of t(16;21)(p11;q22) and t(16;21)(q24;q22) in pediatric AML: a retrospective study by the I-BFM Study Group

Sanne Noort, Martin Zimmermann, Dirk Reinhardt, Wendy Cuccuini, Martina Pigazzi, Jenny Smith, Rhonda E. Ries, Todd A. Alonzo, Betsy Hirsch, Daisuke Tomizawa, Franco Locatelli, Tanja A. Gruber, Susana Raimondi, Edwin Sonneveld, Daniel K. Cheuk, Michael Dworzak, Jan Stary, Jonas Abrahamsson, Nira Arad-Cohen, Malgorzata Czogala, Barbara De Moerloose, Henrik Hasle, Soheil Meshinchi, Marry van den Heuvel-Eibrink and C. Michel Zwaan

Key Points

  • t(16;21) translocations in AML comprise t(16;21)(p11;q22) (FUS-ERG) as well as t(16;21)(q24;q22) (RUNX1-CBFA2T3).

  • Survival in pediatric AML with FUS-ERG is poor, whereas survival in RUNX1-CBFA2T3 is similar to other core-binding factor leukemias.

Abstract

To study the prognostic relevance of rare genetic aberrations in acute myeloid leukemia (AML), such as t(16;21), international collaboration is required. Two different types of t(16;21) translocations can be distinguished: t(16;21)(p11;q22), resulting in the FUS-ERG fusion gene; and t(16;21)(q24;q22), resulting in RUNX1-core binding factor (CBFA2T3). We collected data on clinical and biological characteristics of 54 pediatric AML cases with t(16;21) rearrangements from 14 international collaborative study groups participating in the international Berlin-Frankfurt-Münster (I-BFM) AML study group. The AML-BFM cohort diagnosed between 1997 and 2013 was used as a reference cohort. RUNX1-CBFA2T3 (n = 23) had significantly lower median white blood cell count (12.5 × 109/L, P = .03) compared with the reference cohort. FUS-ERG rearranged AML (n = 31) had no predominant French-American-British (FAB) type, whereas 76% of RUNX1-CBFA2T3 had an M1/M2 FAB type (M1, M2), significantly different from the reference cohort (P = .004). Four-year event-free survival (EFS) of patients with FUS-ERG was 7% (standard error [SE] = 5%), significantly lower compared with the reference cohort (51%, SE = 1%, P < .001). Four-year EFS of RUNX1-CBFA2T3 was 77% (SE = 8%, P = .06), significantly higher compared with the reference cohort. Cumulative incidence of relapse was 74% (SE = 8%) in FUS-ERG, 0% (SE = 0%) in RUNX1-CBFA2T3, compared with 32% (SE = 1%) in the reference cohort (P < .001). Multivariate analysis identified both FUS-ERG and RUNX1-CBFA2T3 as independent risk factors with hazard ratios of 1.9 (P < .0001) and 0.3 (P = .025), respectively. These results describe 2 clinically relevant distinct subtypes of pediatric AML. Similarly to other core-binding factor AMLs, patients with RUNX1-CBFA2T3 rearranged AML may benefit from stratification in the standard risk treatment, whereas patients with FUS-ERG rearranged AML should be considered high-risk.

  • Submitted May 3, 2018.
  • Accepted August 14, 2018.
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