title: Normal karyotype acute myeloid leukemia patients with CEBPA double mutation have a favorable prognosis but no survival benefit from allogeneic stem cell transplant.
abstract: Normal karyotype acute myeloid leukemia (NK-AML) with CCAAT/enhancer binding protein α (CEBPA) mutations is known to have a more favorable prognosis. However, direct comparison of the clinical significance according to consolidation therapy has not been widely performed in patients with NK-AML. A total of 404 patients with NK-AML who received intensive induction chemotherapy were included in the present study. Diagnostic samples from the patients were evaluated for CEBPA mutations by direct sequencing. CEBPA single (sm) or double mutation (dm) was observed in 27 (6.7 %) and 51 (12.6 %) patients, respectively. CEBPA (dm) was associated with GATA2 (mut), and it was less frequently associated with FLT3-ITD(pos), NPM1 (mut), and DNMT3A (mut) in comparison with CEBPA (wild) or CEBPA (sm) (all p values <0.05). On multivariate analysis, CEBPA (dm) (p = 0.007, OR 39.593) was an independent risk factor for achievement of complete remission (CR). With a median follow-up of 40.1 months, CEBPA (dm) showed a favorable overall survival (OS), event-free survival (EFS), and lower relapse incidence (RI) in comparison with CEBPA (wild) (all p values <0.005). Comparison of clinical outcome analyses (consolidation chemotherapy vs. allogeneic hematopoietic cell transplantation (HCT)) demonstrated the role of consolidation treatment in patients with CEBPA (dm). Allogeneic HCT was associated with lower EFS and RI and a trend of higher non-relapse mortality. However, there was no statistically significant difference in OS. In conclusion, CEBPA (dm) was associated with other molecular mutations. Consolidation chemotherapy alone may overcome higher relapse rates by reducing the treatment mortality and increasing survival after relapse events in patients with CEBPA (dm) in NK-AML.
authors.affiliation: Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322 Seoyangro, Hwasun, Jeollanamdo, 519-763, Republic of Korea.
authors.forename: Jae-Sook
authors.initials: JS
authors.lastname: Ahn
authors.affiliation: Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322 Seoyangro, Hwasun, Jeollanamdo, 519-763, Republic of Korea.
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322 Seoyangro, Hwasun, Jeollanamdo, 519-763, Republic of Korea. hjoonk@chonnam.ac.kr.
authors.forename: Hyeoung-Joon
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322 Seoyangro, Hwasun, Jeollanamdo, 519-763, Republic of Korea.
authors.forename: Yeo-Kyeoung
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322 Seoyangro, Hwasun, Jeollanamdo, 519-763, Republic of Korea.
authors.forename: Seung-Shin
authors.initials: SS
authors.lastname: Lee
authors.affiliation: Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322 Seoyangro, Hwasun, Jeollanamdo, 519-763, Republic of Korea.
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Jung
authors.affiliation: Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322 Seoyangro, Hwasun, Jeollanamdo, 519-763, Republic of Korea.
authors.forename: Deok-Hwan
authors.initials: DH
authors.lastname: Yang
authors.affiliation: Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322 Seoyangro, Hwasun, Jeollanamdo, 519-763, Republic of Korea.
authors.forename: Je-Jung
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Genomic Research Center for Hematopoietic Diseases, Chonnam National University Hwasun Hospital, Hwasun, Jeollanam-do, Republic of Korea.
authors.forename: Nan Young
authors.initials: NY
authors.lastname: Kim
authors.affiliation: Genomic Research Center for Hematopoietic Diseases, Chonnam National University Hwasun Hospital, Hwasun, Jeollanam-do, Republic of Korea.
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Choi
authors.affiliation: Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Minden
authors.affiliation: Division of Hematology-Oncology, Samsung Medical Center, Seoul, South Korea.
authors.forename: Chul Won
authors.initials: CW
authors.lastname: Jung
authors.affiliation: Division of Hematology-Oncology, Samsung Medical Center, Seoul, South Korea.
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: Jang
authors.affiliation: Department of Hematology, Cancer Research Institute, Seoul St. Mary's Hospital, Colllege of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Hee Je
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Hematology-Oncology, Kyungpook National University Hospital, Daegu, South Korea.
authors.forename: Joon Ho
authors.initials: JH
authors.lastname: Moon
authors.affiliation: Department of Hematology-Oncology, Kyungpook National University Hospital, Daegu, South Korea.
authors.forename: Sang Kyun
authors.initials: SK
authors.lastname: Sohn
authors.affiliation: Department of Hematology-Oncology, Soon Chun Hyang University Hospital, Seoul, South Korea.
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Won
authors.affiliation: Department of Hematology-Oncology, Dong-A University College of Medicine, Busan, South Korea.
authors.forename: Sung-Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada.
authors.forename: Dennis Dong Hwan
authors.initials: DD
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000639:trends; D006801:Humans; D059785:Karyotype; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D000090243:Nucleophosmin; D011379:Prognosis; D014184:Transplantation, Homologous / Q000379:methods / Q000639:trends; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; C000716967:NPM1 protein, human; D000090243:Nucleophosmin
keywords: Acute myeloid leukemia; Allogeneic hematopoietic cell transplantation; CEBPA; Chemotherapy