Xi Chen1, Xingjuan Wang2, Hu Dou3, Zhenzhen Yang4, Junqin Bi5, Yi Huang6, Ling Lu7, Jie Yu8, Liming Bao9. 1. Center for Clinical Molecular Medicine, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China. 2. Center for Reproductive Medicine, Baoji Maternal and Child Health Hospital, Shanxi, China. 3. Department of Clinical Laboratory, Key Laboratory of Pediatrics in Chongqing, Children's Hospital of Chongqing Medical University, Chongqing, China. 4. Department of Clinical Laboratory, Nanchong Central Hospital, Nanchong, Sichuan, China. 5. Department of Laboratory Medicine, The Second Affiliated Hospital of Kunming Medical University, Kunming, China. 6. Chongqing Key Laboratory of Child Infection and Immunity, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China. 7. Department of Rheumatology, Huashan Hospital, Fudan University, Shanghai, China. 8. Department of Hematology and Oncology, Children's Hospital of Chongqing Medical University, No. 136 Zhongshang 2nd Road, Chongqing, 400014, China. 1808106657@qq.com. 9. Department of Pathology, School of Medicine, University of Colorado Anschutz Medical Campus, 12705 E. Montview Boulevard, Suite 400, Aurora, CO, 80045, USA. Liming.Bao@cuanschutz.edu.
Abstract
BACKGROUND: Acute myeloid leukemia (AML) is rare in children. Although complex karyotype (CK) defined as ≥ 3 cytogenetic abnormalities is an adverse risk factor in adult AML, its prognostic impact on childhood AML remains to be determined. RESULTS: We studied the prevalence, cytogenetic and mutational features, and outcome impact of CK in a cohort of 284 Chinese children with de novo AML. Thirty-four (12.0%) children met the criteria for CK-AML with atypical CK being more frequent than typical CK featured with -5/5q-, -7/7q-, and/or 17p aberration. Mutational prevalence was low and co-occurrence mutants were uncommon. Children with CK-AML showed shorter overall survival (OS) (5-year OS: 26.7 ± 10.6% vs. 37.5 ± 8.6%, p = 0.053) and event-free survival (EFS) (5-year EFS: 26.7 ± 10.6% vs. 38.8 ± 8.6%, p = 0.039) compared with those with intermediate-risk genetics. Typical CK tended to correlate with a decreased OS than atypical CK (5-year OS: 0 vs. 33 ± 12.7%.; p = 0.084), and CK with ≥ 5 cytogenetic aberrations was associated with an inferior survival compared with CK with ≤ 4 aberrations (5-year OS: 13.6 ± 11.7% vs. 50.0 ± 18.6%; p = 0.040; 5-year EFS: 13.6 ± 11.7% vs. 50.0 ± 18.6%; p = 0.048). CONCLUSION: Our results demonstrate CK as an adverse risk factor for reduced survival in childhood AML. Our findings shed light on the cytogenetic and mutational profile of childhood CK-AML and would inform refinement of risk stratification in childhood AML to improve outcomes.
BACKGROUND:Acute myeloid leukemia (AML) is rare in children. Although complex karyotype (CK) defined as ≥ 3 cytogenetic abnormalities is an adverse risk factor in adult AML, its prognostic impact on childhood AML remains to be determined. RESULTS: We studied the prevalence, cytogenetic and mutational features, and outcome impact of CK in a cohort of 284 Chinese children with de novo AML. Thirty-four (12.0%) children met the criteria for CK-AML with atypical CK being more frequent than typical CK featured with -5/5q-, -7/7q-, and/or 17p aberration. Mutational prevalence was low and co-occurrence mutants were uncommon. Children with CK-AML showed shorter overall survival (OS) (5-year OS: 26.7 ± 10.6% vs. 37.5 ± 8.6%, p = 0.053) and event-free survival (EFS) (5-year EFS: 26.7 ± 10.6% vs. 38.8 ± 8.6%, p = 0.039) compared with those with intermediate-risk genetics. Typical CK tended to correlate with a decreased OS than atypical CK (5-year OS: 0 vs. 33 ± 12.7%.; p = 0.084), and CK with ≥ 5 cytogenetic aberrations was associated with an inferior survival compared with CK with ≤ 4 aberrations (5-year OS: 13.6 ± 11.7% vs. 50.0 ± 18.6%; p = 0.040; 5-year EFS: 13.6 ± 11.7% vs. 50.0 ± 18.6%; p = 0.048). CONCLUSION: Our results demonstrate CK as an adverse risk factor for reduced survival in childhood AML. Our findings shed light on the cytogenetic and mutational profile of childhood CK-AML and would inform refinement of risk stratification in childhood AML to improve outcomes.
Authors: Hartmut Döhner; Elihu Estey; David Grimwade; Sergio Amadori; Frederick R Appelbaum; Thomas Büchner; Hervé Dombret; Benjamin L Ebert; Pierre Fenaux; Richard A Larson; Ross L Levine; Francesco Lo-Coco; Tomoki Naoe; Dietger Niederwieser; Gert J Ossenkoppele; Miguel Sanz; Jorge Sierra; Martin S Tallman; Hwei-Fang Tien; Andrew H Wei; Bob Löwenberg; Clara D Bloomfield Journal: Blood Date: 2016-11-28 Impact factor: 22.113
Authors: D Grimwade; H Walker; G Harrison; F Oliver; S Chatters; C J Harrison; K Wheatley; A K Burnett; A H Goldstone Journal: Blood Date: 2001-09-01 Impact factor: 22.113
Authors: Ursula Creutzig; Matthew A Kutny; Ronald Barr; Richard F Schlenk; Raul C Ribeiro Journal: Pediatr Blood Cancer Date: 2018-04-18 Impact factor: 3.167
Authors: M L Slovak; K J Kopecky; P A Cassileth; D H Harrington; K S Theil; A Mohamed; E Paietta; C L Willman; D R Head; J M Rowe; S J Forman; F R Appelbaum Journal: Blood Date: 2000-12-15 Impact factor: 22.113
Authors: Stefan Fröhling; Richard F Schlenk; Sabine Kayser; Martina Morhardt; Axel Benner; Konstanze Döhner; Hartmut Döhner Journal: Blood Date: 2006-07-13 Impact factor: 22.113
Authors: Andrea Pession; Riccardo Masetti; Carmelo Rizzari; Maria Caterina Putti; Fiorina Casale; Franca Fagioli; Matteo Luciani; Luca Lo Nigro; Giuseppe Menna; Concetta Micalizzi; Nicola Santoro; Anna Maria Testi; Marco Zecca; Andrea Biondi; Martina Pigazzi; Sergio Rutella; Roberto Rondelli; Giuseppe Basso; Franco Locatelli Journal: Blood Date: 2013-05-14 Impact factor: 22.113
Authors: Daniel A Arber; Attilio Orazi; Robert Hasserjian; Jürgen Thiele; Michael J Borowitz; Michelle M Le Beau; Clara D Bloomfield; Mario Cazzola; James W Vardiman Journal: Blood Date: 2016-04-11 Impact factor: 22.113
Authors: Piotr Obszański; Anna Kozłowska; Jakub Wańcowiat; Julia Twardowska; Monika Lejman; Joanna Zawitkowska Journal: Molecules Date: 2022-06-18 Impact factor: 4.927