Ahn, Jae-Sook; Kim, Jae-Young; Kim, Hyeoung-Joon; Kim, Yeo-Kyeoung; Lee, Seung-Shin; Jung, Sung-Hoon; Yang, Deok-Hwan; Lee, Je-Jung; Kim, Nan Young; Choi, Seung Hyun; Minden, Mark D; Jung, Chul Won; Jang, Jun-Ho; Kim, Hee Je; Moon, Joon Ho; Sohn, Sang Kyun; Won, Jong-Ho; Kim, Sung-Hyun; Kim, Dennis Dong Hwan
Annals of hematology
2016Jan ; 95 ( 2 ) :301-10.
PMID : 26537612
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Ahn, Jae-Sook - Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322 Seoyangro, Hwasun, Jeollanamdo, 519-763, Republic of Korea.
Kim, Jae-Young - Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322 Seoyangro, Hwasun, Jeollanamdo, 519-763, Republic of Korea.
Kim, Hyeoung-Joon - Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322 Seoyangro, Hwasun, Jeollanamdo, 519-763, Republic of Korea. hjoonk@chonnam.ac.kr.
Kim, Yeo-Kyeoung - Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322 Seoyangro, Hwasun, Jeollanamdo, 519-763, Republic of Korea.
Lee, Seung-Shin - Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322 Seoyangro, Hwasun, Jeollanamdo, 519-763, Republic of Korea.
Jung, Sung-Hoon - Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322 Seoyangro, Hwasun, Jeollanamdo, 519-763, Republic of Korea.
Yang, Deok-Hwan - Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322 Seoyangro, Hwasun, Jeollanamdo, 519-763, Republic of Korea.
Lee, Je-Jung - Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322 Seoyangro, Hwasun, Jeollanamdo, 519-763, Republic of Korea.
Kim, Nan Young - Genomic Research Center for Hematopoietic Diseases, Chonnam National University Hwasun Hospital, Hwasun, Jeollanam-do, Republic of Korea.
Choi, Seung Hyun - Genomic Research Center for Hematopoietic Diseases, Chonnam National University Hwasun Hospital, Hwasun, Jeollanam-do, Republic of Korea.
Minden, Mark D - Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada.
Jung, Chul Won - Division of Hematology-Oncology, Samsung Medical Center, Seoul, South Korea.
Jang, Jun-Ho - Division of Hematology-Oncology, Samsung Medical Center, Seoul, South Korea.
Kim, Hee Je - Department of Hematology, Cancer Research Institute, Seoul St. Mary's Hospital, Colllege of Medicine, The Catholic University of Korea, Seoul, South Korea.
Moon, Joon Ho - Department of Hematology-Oncology, Kyungpook National University Hospital, Daegu, South Korea.
Sohn, Sang Kyun - Department of Hematology-Oncology, Kyungpook National University Hospital, Daegu, South Korea.
Won, Jong-Ho - Department of Hematology-Oncology, Soon Chun Hyang University Hospital, Seoul, South Korea.
Kim, Sung-Hyun - Department of Hematology-Oncology, Dong-A University College of Medicine, Busan, South Korea.
Kim, Dennis Dong Hwan - Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada.
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.
keyword
Acute myeloid leukemia; Allogeneic hematopoietic cell transplantation; CEBPA; Chemotherapy
MESH
Adolescent, Adult, Aged, Aged, 80 and over, CCAAT-Enhancer-Binding Proteins/*genetics, Disease-Free Survival, Female, Follow-Up Studies, Hematopoietic Stem Cell Transplantation/*methods/trends, Humans, *Karyotype, Leukemia, Myeloid, Acute/diagnosis/*genetics/*therapy, Male, Middle Aged, Mutation/*genetics, Prognosis, Transplantation, Homologous/methods/trends, Treatment Outcome, Young Adult
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