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 & 5 others Barbara De Moerloose, Henrik Hasle, Soheil Meshinchi, Marry van den Heuvel-Eibrink, C Michel Zwaan

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1584-1592
Number of pages9
JournalBlood
Volume132
Issue number15
DOIs
Publication statusPublished - Oct 11 2018

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Berlin
Acute Myeloid Leukemia
Retrospective Studies
Pediatrics
Core Binding Factors
Disease-Free Survival
Gene Fusion
Leukocyte Count
Multivariate Analysis
Recurrence
Incidence

Cite this

Noort, S., Zimmermann, M., Reinhardt, D., Cuccuini, W., Pigazzi, M., Smith, J., ... Zwaan, C. M. (2018). 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. Blood, 132(15), 1584-1592. https://doi.org/10.1182/blood-2018-05-849059

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

In: Blood, Vol. 132, No. 15, 11.10.2018, p. 1584-1592.

Research output: Contribution to journalArticle

Noort, S, Zimmermann, M, Reinhardt, D, Cuccuini, W, Pigazzi, M, Smith, J, Ries, RE, Alonzo, TA, Hirsch, B, Tomizawa, D, Locatelli, F, Gruber, TA, Raimondi, S, Sonneveld, E, Cheuk, DK, Dworzak, M, Stary, J, Abrahamsson, J, Arad-Cohen, N, Czogala, M, De Moerloose, B, Hasle, H, Meshinchi, S, van den Heuvel-Eibrink, M & Zwaan, CM 2018, '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', Blood, vol. 132, no. 15, pp. 1584-1592. https://doi.org/10.1182/blood-2018-05-849059
Noort, Sanne ; Zimmermann, Martin ; Reinhardt, Dirk ; Cuccuini, Wendy ; Pigazzi, Martina ; Smith, Jenny ; Ries, Rhonda E ; Alonzo, Todd A ; Hirsch, Betsy ; Tomizawa, Daisuke ; Locatelli, Franco ; Gruber, Tanja A ; Raimondi, Susana ; Sonneveld, Edwin ; Cheuk, Daniel K ; Dworzak, Michael ; Stary, Jan ; Abrahamsson, Jonas ; Arad-Cohen, Nira ; Czogala, Malgorzata ; De Moerloose, Barbara ; Hasle, Henrik ; Meshinchi, Soheil ; van den Heuvel-Eibrink, Marry ; Zwaan, C Michel. / 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. In: Blood. 2018 ; Vol. 132, No. 15. pp. 1584-1592.
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title = "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",
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-M{\"u}nster (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.",
author = "Sanne Noort and Martin Zimmermann and Dirk Reinhardt and Wendy Cuccuini and Martina Pigazzi and Jenny Smith and Ries, {Rhonda E} and Alonzo, {Todd A} and Betsy Hirsch and Daisuke Tomizawa and Franco Locatelli and Gruber, {Tanja A} and Susana Raimondi and Edwin Sonneveld and Cheuk, {Daniel K} and Michael Dworzak and Jan Stary and Jonas Abrahamsson and Nira Arad-Cohen and Malgorzata Czogala and {De Moerloose}, Barbara and Henrik Hasle and Soheil Meshinchi and {van den Heuvel-Eibrink}, Marry and Zwaan, {C Michel}",
note = "{\circledC} 2018 by The American Society of Hematology.",
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TY - JOUR

T1 - Prognostic impact of t(16;21)(p11;q22) and t(16;21)(q24;q22) in pediatric AML

T2 - a retrospective study by the I-BFM Study Group

AU - Noort, Sanne

AU - Zimmermann, Martin

AU - Reinhardt, Dirk

AU - Cuccuini, Wendy

AU - Pigazzi, Martina

AU - Smith, Jenny

AU - Ries, Rhonda E

AU - Alonzo, Todd A

AU - Hirsch, Betsy

AU - Tomizawa, Daisuke

AU - Locatelli, Franco

AU - Gruber, Tanja A

AU - Raimondi, Susana

AU - Sonneveld, Edwin

AU - Cheuk, Daniel K

AU - Dworzak, Michael

AU - Stary, Jan

AU - Abrahamsson, Jonas

AU - Arad-Cohen, Nira

AU - Czogala, Malgorzata

AU - De Moerloose, Barbara

AU - Hasle, Henrik

AU - Meshinchi, Soheil

AU - van den Heuvel-Eibrink, Marry

AU - Zwaan, C Michel

N1 - © 2018 by The American Society of Hematology.

PY - 2018/10/11

Y1 - 2018/10/11

N2 - 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.

AB - 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.

U2 - 10.1182/blood-2018-05-849059

DO - 10.1182/blood-2018-05-849059

M3 - Article

VL - 132

SP - 1584

EP - 1592

JO - Blood

JF - Blood

SN - 0006-4971

IS - 15

ER -